Method for Using Gene Expression to Determine Prognosis of Prostate Cancer

Information

  • Patent Application
  • 20200255911
  • Publication Number
    20200255911
  • Date Filed
    February 25, 2020
    4 years ago
  • Date Published
    August 13, 2020
    3 years ago
Abstract
Molecular assays that involve measurement of expression levels of prognostic biomarkers, or co-expressed biomarkers, from a biological sample obtained from a prostate cancer patient, and analysis of the measured expression levels to provide information concerning the likely prognosis for said patient, and likelihood that said patient will have a recurrence of prostate cancer, or to classify the tumor by likelihood of clinical outcome or TMPRSS2 fusion status, are provided herein.
Description
TECHNICAL FIELD

The present disclosure relates to molecular diagnostic assays that provide information concerning methods to use gene expression profiles to determine prognostic information for cancer patients. Specifically, the present disclosure provides genes and microRNAs, the expression levels of which may be used to determine the likelihood that a prostate cancer patient will experience a local or distant cancer recurrence.


INTRODUCTION

Prostate cancer is the most common solid malignancy in men and the second most common cause of cancer-related death in men in North America and the European Union (EU). In 2008, over 180,000 patients will be diagnosed with prostate cancer in the United States alone and nearly 30,000 will die of this disease. Age is the single most important risk factor for the development of prostate cancer, and applies across all racial groups that have been studied. With the aging of the U.S. population, it is projected that the annual incidence of prostate cancer will double by 2025 to nearly 400,000 cases per year.


Since the introduction of prostate-specific antigen (PSA) screening in the 1990's, the proportion of patients presenting with clinically evident disease has fallen dramatically such that patients categorized as “low risk” now constitute half of new diagnoses today. PSA is used as a tumor marker to determine the presence of prostate cancer as high PSA levels are associated with prostate cancer. Despite a growing proportion of localized prostate cancer patients presenting with low-risk features such as low stage (T1) disease, greater than 90% of patients in the US still undergo definitive therapy, including prostatectomy or radiation. Only about 15% of these patients would develop metastatic disease and die from their prostate cancer, even in the absence of definitive therapy. A. Bill-Axelson, et al., J Nat'l Cancer Inst. 100(16):1144-1154 (2008). Therefore, the majority of prostate cancer patients are being over-treated.


Estimates of recurrence risk and treatment decisions in prostate cancer are currently based primarily on PSA levels and/or tumor stage. Although tumor stage has been demonstrated to have significant association with outcome sufficient to be included in pathology reports, the College of American Pathologists Consensus Statement noted that variations in approach to the acquisition, interpretation, reporting, and analysis of this information exist. C. Compton, et al., Arch Pathol Lab Med 124:979-992 (2000). As a consequence, existing pathologic staging methods have been criticized as lacking reproducibility and therefore may provide imprecise estimates of individual patient risk.


SUMMARY

This application discloses molecular assays that involve measurement of expression level(s) of one or more genes, gene subsets, microRNAs, or one or more microRNAs in combination with one or more genes or gene subsets, from a biological sample obtained from a prostate cancer patient, and analysis of the measured expression levels to provide information concerning the likelihood of cancer recurrence. For example, the likelihood of cancer recurrence could be described in terms of a score based on clinical or biochemical recurrence-free interval.


In addition, this application discloses molecular assays that involve measurement of expression level(s) of one or more genes, gene subsets, microRNAs, or one or more microRNAs in combination with one or more genes or gene subsets, from a biological sample obtained to identify a risk classification for a prostate cancer patient. For example, patients may be stratified using expression level(s) of one or more genes or microRNAs associated, positively or negatively, with cancer recurrence or death from cancer, or with a prognostic factor. In an exemplary embodiment, the prognostic factor is Gleason pattern.


The biological sample may be obtained from standard methods, including surgery, biopsy, or bodily fluids. It may comprise tumor tissue or cancer cells, and, in some cases, histologically normal tissue, e.g., histologically normal tissue adjacent the tumor tissue. In exemplary embodiments, the biological sample is positive or negative for a TMPRSS2 fusion.


In exemplary embodiments, expression level(s) of one or more genes and/or microRNAs that are associated, positively or negatively, with a particular clinical outcome in prostate cancer are used to determine prognosis and appropriate therapy. The genes disclosed herein may be used alone or arranged in functional gene subsets, such as cell adhesion/migration, immediate-early stress response, and extracellular matrix-associated. Each gene subset comprises the genes disclosed herein, as well as genes that are co-expressed with one or more of the disclosed genes. The calculation may be performed on a computer, programmed to execute the gene expression analysis. The microRNAs disclosed herein may also be used alone or in combination with any one or more of the microRNAs and/or genes disclosed.


In exemplary embodiments, the molecular assay may involve expression levels for at least two genes. The genes, or gene subsets, may be weighted according to strength of association with prognosis or tumor microenvironment. In another exemplary embodiment, the molecular assay may involve expression levels of at least one gene and at least one microRNA. The gene-microRNA combination may be selected based on the likelihood that the gene-microRNA combination functionally interact.





BRIEF DESCRIPTION OF THE DRAWING


FIG. 1 shows the distribution of clinical and pathology assessments of biopsy Gleason score, baseline PSA level, and clinical T-stage.





DEFINITIONS

Unless defined otherwise, technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Singleton et al., Dictionary of Microbiology and Molecular Biology 2nd ed., J. Wiley & Sons (New York, N.Y. 1994), and March, Advanced Organic Chemistry Reactions, Mechanisms and Structure 4th ed., John Wiley & Sons (New York, N.Y. 1992), provide one skilled in the art with a general guide to many of the terms used in the present application.


One skilled in the art will recognize many methods and materials similar or equivalent to those described herein, which could be used in the practice of the present invention. Indeed, the present invention is in no way limited to the methods and materials described herein. For purposes of the invention, the following terms are defined below.


The terms “tumor” and “lesion” as used herein, refer to all neoplastic cell growth and proliferation, whether malignant or benign, and all pre-cancerous and cancerous cells and tissues. Those skilled in the art will realize that a tumor tissue sample may comprise multiple biological elements, such as one or more cancer cells, partial or fragmented cells, tumors in various stages, surrounding histologically normal-appearing tissue, and/or macro or micro-dissected tissue.


The terms “cancer” and “cancerous” refer to or describe the physiological condition in mammals that is typically characterized by unregulated cell growth. Examples of cancer in the present disclosure include cancer of the urogenital tract, such as prostate cancer.


The “pathology” of cancer includes all phenomena that compromise the well-being of the patient. This includes, without limitation, abnormal or uncontrollable cell growth, metastasis, interference with the normal functioning of neighboring cells, release of cytokines or other secretory products at abnormal levels, suppression or aggravation of inflammatory or immunological response, neoplasia, premalignancy, malignancy, invasion of surrounding or distant tissues or organs, such as lymph nodes, etc.


As used herein, the term “prostate cancer” is used interchangeably and in the broadest sense refers to all stages and all forms of cancer arising from the tissue of the prostate gland.


According to the tumor, node, metastasis (TNM) staging system of the American Joint Committee on Cancer (AJCC), AJCC Cancer Staging Manual (7th Ed., 2010), the various stages of prostate cancer are defined as follows: Tumor: T1: clinically inapparent tumor not palpable or visible by imaging, T1a: tumor incidental histological finding in 5% or less of tissue resected, T1b: tumor incidental histological finding in more than 5% of tissue resected, T1c: tumor identified by needle biopsy; T2: tumor confined within prostate, T2a: tumor involves one half of one lobe or less, T2b: tumor involves more than half of one lobe, but not both lobes, T2c: tumor involves both lobes; T3: tumor extends through the prostatic capsule, T3a: extracapsular extension (unilateral or bilateral), T3b: tumor invades seminal vesicle(s); T4: tumor is fixed or invades adjacent structures other than seminal vesicles (bladder neck, external sphincter, rectum, levator muscles, or pelvic wall). Node: NO: no regional lymph node metastasis; N1: metastasis in regional lymph nodes. Metastasis: M0: no distant metastasis; M1: distant metastasis present.


The Gleason Grading system is used to help evaluate the prognosis of men with prostate cancer. Together with other parameters, it is incorporated into a strategy of prostate cancer staging, which predicts prognosis and helps guide therapy. A Gleason “score” or “grade” is given to prostate cancer based upon its microscopic appearance. Tumors with a low Gleason score typically grow slowly enough that they may not pose a significant threat to the patients in their lifetimes. These patients are monitored (“watchful waiting” or “active surveillance”) over time. Cancers with a higher Gleason score are more aggressive and have a worse prognosis, and these patients are generally treated with surgery (e.g., radical prostectomy) and, in some cases, therapy (e.g., radiation, hormone, ultrasound, chemotherapy). Gleason scores (or sums) comprise grades of the two most common tumor patterns. These patterns are referred to as Gleason patterns 1-5, with pattern 1 being the most well-differentiated. Most have a mixture of patterns. To obtain a Gleason score or grade, the dominant pattern is added to the second most prevalent pattern to obtain a number between 2 and 10. The Gleason Grades include: G1: well differentiated (slight anaplasia) (Gleason 2-4); G2: moderately differentiated (moderate anaplasia) (Gleason 5-6); G3-4: poorly differentiated/undifferentiated (marked anaplasia) (Gleason 7-10).


Stage groupings: Stage I: T1a N0 M0 G1; Stage II: (T1a N0 M0 G2-4) or (T1b, c, T1, T2, N0 M0 Any G); Stage III: T3 N0 M0 Any G; Stage IV: (T4 N0 M0 Any G) or (Any T N1 M0 Any G) or (Any T Any N M1 Any G).


As used herein, the term “tumor tissue” refers to a biological sample containing one or more cancer cells, or a fraction of one or more cancer cells. Those skilled in the art will recognize that such biological sample may additionally comprise other biological components, such as histologically appearing normal cells (e.g., adjacent the tumor), depending upon the method used to obtain the tumor tissue, such as surgical resection, biopsy, or bodily fluids.


As used herein, the term “AUA risk group” refers to the 2007 updated American Urological Association (AUA) guidelines for management of clinically localized prostate cancer, which clinicians use to determine whether a patient is at low, intermediate, or high risk of biochemical (PSA) relapse after local therapy.


As used herein, the term “adjacent tissue (AT)” refers to histologically “normal” cells that are adjacent a tumor. For example, the AT expression profile may be associated with disease recurrence and survival.


As used herein “non-tumor prostate tissue” refers to histologically normal-appearing tissue adjacent a prostate tumor.


Prognostic factors are those variables related to the natural history of cancer, which influence the recurrence rates and outcome of patients once they have developed cancer. Clinical parameters that have been associated with a worse prognosis include, for example, increased tumor stage, PSA level at presentation, and Gleason grade or pattern. Prognostic factors are frequently used to categorize patients into subgroups with different baseline relapse risks.


The term “prognosis” is used herein to refer to the likelihood that a cancer patient will have a cancer-attributable death or progression, including recurrence, metastatic spread, and drug resistance, of a neoplastic disease, such as prostate cancer. For example, a “good prognosis” would include long term survival without recurrence and a “bad prognosis” would include cancer recurrence.


As used herein, the term “expression level” as applied to a gene refers to the normalized level of a gene product, e.g. the normalized value determined for the RNA expression level of a gene or for the polypeptide expression level of a gene.


The term “gene product” or “expression product” are used herein to refer to the RNA (ribonucleic acid) transcription products (transcripts) of the gene, including mRNA, and the polypeptide translation products of such RNA transcripts. A gene product can be, for example, an unspliced RNA, an mRNA, a splice variant mRNA, a microRNA, a fragmented RNA, a polypeptide, a post-translationally modified polypeptide, a splice variant polypeptide, etc.


The term “RNA transcript” as used herein refers to the RNA transcription products of a gene, including, for example, mRNA, an unspliced RNA, a splice variant mRNA, a microRNA, and a fragmented RNA.


The term “microRNA” is used herein to refer to a small, non-coding, single-stranded RNA of ˜18-25 nucleotides that may regulate gene expression. For example, when associated with the RNA-induced silencing complex (RISC), the complex binds to specific mRNA targets and causes translation repression or cleavage of these mRNA sequences.


Unless indicated otherwise, each gene name used herein corresponds to the Official Symbol assigned to the gene and provided by Entrez Gene (URL: www.ncbi.nlm.nih.gov/sites/entrez) as of the filing date of this application.


The terms “correlated” and “associated” are used interchangeably herein to refer to the association between two measurements (or measured entities). The disclosure provides genes, gene subsets, microRNAs, or microRNAs in combination with genes or gene subsets, the expression levels of which are associated with tumor stage. For example, the increased expression level of a gene or microRNA may be positively correlated (positively associated) with a good or positive prognosis. Such a positive correlation may be demonstrated statistically in various ways, e.g. by a cancer recurrence hazard ratio less than one. In another example, the increased expression level of a gene or microRNA may be negatively correlated (negatively associated) with a good or positive prognosis. In that case, for example, the patient may experience a cancer recurrence.


The terms “good prognosis” or “positive prognosis” as used herein refer to a beneficial clinical outcome, such as long-term survival without recurrence. The terms “bad prognosis” or “negative prognosis” as used herein refer to a negative clinical outcome, such as cancer recurrence.


The term “risk classification” means a grouping of subjects by the level of risk (or likelihood) that the subject will experience a particular clinical outcome. A subject may be classified into a risk group or classified at a level of risk based on the methods of the present disclosure, e.g. high, medium, or low risk. A “risk group” is a group of subjects or individuals with a similar level of risk for a particular clinical outcome.


The term “long-term” survival is used herein to refer to survival for a particular time period, e.g., for at least 5 years, or for at least 10 years.


The term “recurrence” is used herein to refer to local or distant recurrence (i.e., metastasis) of cancer. For example, prostate cancer can recur locally in the tissue next to the prostate or in the seminal vesicles. The cancer may also affect the surrounding lymph nodes in the pelvis or lymph nodes outside this area. Prostate cancer can also spread to tissues next to the prostate, such as pelvic muscles, bones, or other organs. Recurrence can be determined by clinical recurrence detected by, for example, imaging study or biopsy, or biochemical recurrence detected by, for example, sustained follow-up prostate-specific antigen (PSA) levels ≥0.4 ng/mL or the initiation of salvage therapy as a result of a rising PSA level.


The term “clinical recurrence-free interval (cRFI)” is used herein as time (in months) from surgery to first clinical recurrence or death due to clinical recurrence of prostate cancer. Losses due to incomplete follow-up, other primary cancers or death prior to clinical recurrence are considered censoring events; when these occur, the only information known is that up through the censoring time, clinical recurrence has not occurred in this subject. Biochemical recurrences are ignored for the purposes of calculating cRFI.


The term “biochemical recurrence-free interval (bRFI)” is used herein to mean the time (in months) from surgery to first biochemical recurrence of prostate cancer. Clinical recurrences, losses due to incomplete follow-up, other primary cancers, or death prior to biochemical recurrence are considered censoring events.


The term “Overall Survival (OS)” is used herein to refer to the time (in months) from surgery to death from any cause. Losses due to incomplete follow-up are considered censoring events. Biochemical recurrence and clinical recurrence are ignored for the purposes of calculating OS.


The term “Prostate Cancer-Specific Survival (PCSS)” is used herein to describe the time (in years) from surgery to death from prostate cancer. Losses due to incomplete follow-up or deaths from other causes are considered censoring events. Clinical recurrence and biochemical recurrence are ignored for the purposes of calculating PCSS.


The term “upgrading” or “upstaging” as used herein refers to a change in Gleason grade from 3+3 at the time of biopsy to 3+4 or greater at the time of radical prostatectomy (RP), or Gleason grade 3+4 at the time of biopsy to 4+3 or greater at the time of RP, or seminal vessical involvement (SVI), or extracapsular involvement (ECE) at the time of RP.


In practice, the calculation of the measures listed above may vary from study to study depending on the definition of events to be considered censored.


The term “microarray” refers to an ordered arrangement of hybridizable array elements, e.g. oligonucleotide or polynucleotide probes, on a substrate.


The term “polynucleotide” generally refers to any polyribonucleotide or polydeoxribonucleotide, which may be unmodified RNA or DNA or modified RNA or DNA. Thus, for instance, polynucleotides as defined herein include, without limitation, single- and double-stranded DNA, DNA including single- and double-stranded regions, single- and double-stranded RNA, and RNA including single- and double-stranded regions, hybrid molecules comprising DNA and RNA that may be single-stranded or, more typically, double-stranded or include single- and double-stranded regions. In addition, the term “polynucleotide” as used herein refers to triple-stranded regions comprising RNA or DNA or both RNA and DNA. The strands in such regions may be from the same molecule or from different molecules. The regions may include all of one or more of the molecules, but more typically involve only a region of some of the molecules. One of the molecules of a triple-helical region often is an oligonucleotide. The term “polynucleotide” specifically includes cDNAs. The term includes DNAs (including cDNAs) and RNAs that contain one or more modified bases. Thus, DNAs or RNAs with backbones modified for stability or for other reasons, are “polynucleotides” as that term is intended herein. Moreover, DNAs or RNAs comprising unusual bases, such as inosine, or modified bases, such as tritiated bases, are included within the term “polynucleotides” as defined herein. In general, the term “polynucleotide” embraces all chemically, enzymatically and/or metabolically modified forms of unmodified polynucleotides, as well as the chemical forms of DNA and RNA characteristic of viruses and cells, including simple and complex cells.


The term “oligonucleotide” refers to a relatively short polynucleotide, including, without limitation, single-stranded deoxyribonucleotides, single- or double-stranded ribonucleotides, RNArDNA hybrids and double-stranded DNAs. Oligonucleotides, such as single-stranded DNA probe oligonucleotides, are often synthesized by chemical methods, for example using automated oligonucleotide synthesizers that are commercially available. However, oligonucleotides can be made by a variety of other methods, including in vitro recombinant DNA-mediated techniques and by expression of DNAs in cells and organisms.


The term “Ct” as used herein refers to threshold cycle, the cycle number in quantitative polymerase chain reaction (qPCR) at which the fluorescence generated within a reaction well exceeds the defined threshold, i.e. the point during the reaction at which a sufficient number of amplicons have accumulated to meet the defined threshold.


The term “Cp” as used herein refers to “crossing point.” The Cp value is calculated by determining the second derivatives of entire qPCR amplification curves and their maximum value. The Cp value represents the cycle at which the increase of fluorescence is highest and where the logarithmic phase of a PCR begins.


The terms “threshold” or “thresholding” refer to a procedure used to account for non-linear relationships between gene expression measurements and clinical response as well as to further reduce variation in reported patient scores. When thresholding is applied, all measurements below or above a threshold are set to that threshold value. Non-linear relationship between gene expression and outcome could be examined using smoothers or cubic splines to model gene expression in Cox PH regression on recurrence free interval or logistic regression on recurrence status. D. Cox, Journal of the Royal Statistical Society, Series B 34:187-220 (1972). Variation in reported patient scores could be examined as a function of variability in gene expression at the limit of quantitation and/or detection for a particular gene.


As used herein, the term “amplicon,” refers to pieces of DNA that have been synthesized using amplification techniques, such as polymerase chain reactions (PCR) and ligase chain reactions.


“Stringency” of hybridization reactions is readily determinable by one of ordinary skill in the art, and generally is an empirical calculation dependent upon probe length, washing temperature, and salt concentration. In general, longer probes require higher temperatures for proper annealing, while shorter probes need lower temperatures. Hybridization generally depends on the ability of denatured DNA to re-anneal when complementary strands are present in an environment below their melting temperature. The higher the degree of desired homology between the probe and hybridizable sequence, the higher the relative temperature which can be used. As a result, it follows that higher relative temperatures would tend to make the reaction conditions more stringent, while lower temperatures less so. For additional details and explanation of stringency of hybridization reactions, see Ausubel et al., Current Protocols in Molecular Biology (Wiley Interscience Publishers, 1995).


“Stringent conditions” or “high stringency conditions”, as defined herein, typically: (1) employ low ionic strength and high temperature for washing, for example 0.015 M sodium chloride/0.0015 M sodium citrate/0.1% sodium dodecyl sulfate at 50° C.; (2) employ during hybridization a denaturing agent, such as formamide, for example, 50% (v/v) formamide with 0.1% bovine serum albumin/0.1% Ficoll/0.1% polyvinylpyrrolidone/50 mM sodium phosphate buffer at pH 6.5 with 750 mM sodium chloride, 75 mM sodium citrate at 42° C.; or (3) employ 50% formamide, 5×SSC (0.75 M NaCl, 0.075 M sodium citrate), 50 mM sodium phosphate (pH 6.8), 0.1% sodium pyrophosphate, 5×Denhardt's solution, sonicated salmon sperm DNA (50 μg/ml), 0.1% SDS, and 10% dextran sulfate at 42° C., with washes at 42° C. in 0.2×SSC (sodium chloride/sodium citrate) and 50% formamide, followed by a high-stringency wash consisting of 0.1×SSC containing EDTA at 55° C.


“Moderately stringent conditions” may be identified as described by Sambrook et al., Molecular Cloning: A Laboratory Manual, New York: Cold Spring Harbor Press, 1989, and include the use of washing solution and hybridization conditions (e.g., temperature, ionic strength and % SDS) less stringent that those described above. An example of moderately stringent conditions is overnight incubation at 37° C. in a solution comprising: 20% formamide, 5×SSC (150 mM NaCl, 15 mM trisodium citrate), 50 mM sodium phosphate (pH 7.6), 5×Denhardt's solution, 10% dextran sulfate, and 20 mg/ml denatured sheared salmon sperm DNA, followed by washing the filters in 1×SSC at about 37-50° C. The skilled artisan will recognize how to adjust the temperature, ionic strength, etc. as necessary to accommodate factors such as probe length and the like.


The terms “splicing” and “RNA splicing” are used interchangeably and refer to RNA processing that removes introns and joins exons to produce mature mRNA with continuous coding sequence that moves into the cytoplasm of an eukaryotic cell.


The terms “co-express” and “co-expressed”, as used herein, refer to a statistical correlation between the amounts of different transcript sequences across a population of different patients. Pairwise co-expression may be calculated by various methods known in the art, e.g., by calculating Pearson correlation coefficients or Spearman correlation coefficients. Co-expressed gene cliques may also be identified using graph theory. An analysis of co-expression may be calculated using normalized expression data. A gene is said to be co-expressed with a particular disclosed gene when the expression level of the gene exhibits a Pearson correlation coefficient greater than or equal to 0.6.


A “computer-based system” refers to a system of hardware, software, and data storage medium used to analyze information. The minimum hardware of a patient computer-based system comprises a central processing unit (CPU), and hardware for data input, data output (e.g., display), and data storage. An ordinarily skilled artisan can readily appreciate that any currently available computer-based systems and/or components thereof are suitable for use in connection with the methods of the present disclosure. The data storage medium may comprise any manufacture comprising a recording of the present information as described above, or a memory access device that can access such a manufacture.


To “record” data, programming or other information on a computer readable medium refers to a process for storing information, using any such methods as known in the art. Any convenient data storage structure may be chosen, based on the means used to access the stored information. A variety of data processor programs and formats can be used for storage, e.g. word processing text file, database format, etc.


A “processor” or “computing means” references any hardware and/or software combination that will perform the functions required of it. For example, a suitable processor may be a programmable digital microprocessor such as available in the form of an electronic controller, mainframe, server or personal computer (desktop or portable). Where the processor is programmable, suitable programming can be communicated from a remote location to the processor, or previously saved in a computer program product (such as a portable or fixed computer readable storage medium, whether magnetic, optical or solid state device based). For example, a magnetic medium or optical disk may carry the programming, and can be read by a suitable reader communicating with each processor at its corresponding station.


As used herein, the terms “active surveillance” and “watchful waiting” mean closely monitoring a patient's condition without giving any treatment until symptoms appear or change. For example, in prostate cancer, watchful waiting is usually used in older men with other medical problems and early-stage disease.


As used herein, the term “surgery” applies to surgical methods undertaken for removal of cancerous tissue, including pelvic lymphadenectomy, radical prostatectomy, transurethral resection of the prostate (TURP), excision, dissection, and tumor biopsy/removal. The tumor tissue or sections used for gene expression analysis may have been obtained from any of these methods.


As used herein, the term “therapy” includes radiation, hormonal therapy, cryosurgery, chemotherapy, biologic therapy, and high-intensity focused ultrasound.


As used herein, the term “TMPRSS fusion” and “TMPRSS2 fusion” are used interchangeably and refer to a fusion of the androgen-driven TMPRSS2 gene with the ERG oncogene, which has been demonstrated to have a significant association with prostate cancer. S. Perner, et al., Urologe A. 46(7):754-760 (2007); S. A. Narod, et al., Br J Cancer 99(6):847-851 (2008). As used herein, positive TMPRSS fusion status indicates that the TMPRSS fusion is present in a tissue sample, whereas negative TMPRSS fusion status indicates that the TMPRSS fusion is not present in a tissue sample. Experts skilled in the art will recognize that there are numerous ways to determine TMPRSS fusion status, such as real-time, quantitative PCR or high-throughput sequencing. See, e.g., K. Mertz, et al., Neoplasis 9(3):200-206 (2007); C. Maher, Nature 458(7234):97-101 (2009).


Gene Expression Methods Using Genes, Gene Subsets, and MicroRNAs

The present disclosure provides molecular assays that involve measurement of expression level(s) of one or more genes, gene subsets, microRNAs, or one or more microRNAs in combination with one or more genes or gene subsets, from a biological sample obtained from a prostate cancer patient, and analysis of the measured expression levels to provide information concerning the likelihood of cancer recurrence.


The present disclosure further provides methods to classify a prostate tumor based on expression level(s) of one or more genes and/or microRNAs. The disclosure further provides genes and/or microRNAs that are associated, positively or negatively, with a particular prognostic outcome. In exemplary embodiments, the clinical outcomes include cRFI and bRFI. In another embodiment, patients may be classified in risk groups based on the expression level(s) of one or more genes and/or microRNAs that are associated, positively or negatively, with a prognostic factor. In an exemplary embodiment, that prognostic factor is Gleason pattern.


Various technological approaches for determination of expression levels of the disclosed genes and microRNAs are set forth in this specification, including, without limitation, RT-PCR, microarrays, high-throughput sequencing, serial analysis of gene expression (SAGE) and Digital Gene Expression (DGE), which will be discussed in detail below. In particular aspects, the expression level of each gene or microRNA may be determined in relation to various features of the expression products of the gene including exons, introns, protein epitopes and protein activity.


The expression level(s) of one or more genes and/or microRNAs may be measured in tumor tissue. For example, the tumor tissue may obtained upon surgical removal or resection of the tumor, or by tumor biopsy. The tumor tissue may be or include histologically “normal” tissue, for example histologically “normal” tissue adjacent to a tumor. The expression level of genes and/or microRNAs may also be measured in tumor cells recovered from sites distant from the tumor, for example circulating tumor cells, body fluid (e.g., urine, blood, blood fraction, etc.).


The expression product that is assayed can be, for example, RNA or a polypeptide. The expression product may be fragmented. For example, the assay may use primers that are complementary to target sequences of an expression product and could thus measure full transcripts as well as those fragmented expression products containing the target sequence. Further information is provided in Table A (inserted in specification prior to claims).


The RNA expression product may be assayed directly or by detection of a cDNA product resulting from a PCR-based amplification method, e.g., quantitative reverse transcription polymerase chain reaction (qRT-PCR). (See e.g., U.S. Pat. No. 7,587,279). Polypeptide expression product may be assayed using immunohistochemistry (IHC). Further, both RNA and polypeptide expression products may also be is assayed using microarrays.


Clinical Utility

Prostate cancer is currently diagnosed using a digital rectal exam (DRE) and Prostate-specific antigen (PSA) test. If PSA results are high, patients will generally undergo a prostate tissue biopsy. The pathologist will review the biopsy samples to check for cancer cells and determine a Gleason score. Based on the Gleason score, PSA, clinical stage, and other factors, the physician must make a decision whether to monitor the patient, or treat the patient with surgery and therapy.


At present, clinical decision-making in early stage prostate cancer is governed by certain histopathologic and clinical factors. These include: (1) tumor factors, such as clinical stage (e.g. T1, T2), PSA level at presentation, and Gleason grade, that are very strong prognostic factors in determining outcome; and (2) host factors, such as age at diagnosis and co-morbidity. Because of these factors, the most clinically useful means of stratifying patients with localized disease according to prognosis has been through multifactorial staging, using the clinical stage, the serum PSA level, and tumor grade (Gleason grade) together. In the 2007 updated American Urological Association (AUA) guidelines for management of clinically localized prostate cancer, these parameters have been grouped to determine whether a patient is at low, intermediate, or high risk of biochemical (PSA) relapse after local therapy. I. Thompson, et al., Guideline for the management of clinically localized prostate cancer, J Urol. 177(6):2106-31 (2007).


Although such classifications have proven to be helpful in distinguishing patients with localized disease who may need adjuvant therapy after surgery/radiation, they have less ability to discriminate between indolent cancers, which do not need to be treated with local therapy, and aggressive tumors, which require local therapy. In fact, these algorithms are of increasingly limited use for deciding between conservative management and definitive therapy because the bulk of prostate cancers diagnosed in the PSA screening era now present with clinical stage T1c and PSA ≤10 ng/mL.


Patients with T1 prostate cancer have disease that is not clinically apparent but is discovered either at transurethral resection of the prostate (TURP, T1a, T1b) or at biopsy performed because of an elevated PSA (>4 ng/mL, T1c). Approximately 80% of the cases presenting in 2007 are clinical T1 at diagnosis. In a Scandinavian trial, OS at 10 years was 85% for patients with early stage prostate cancer (T1/T2) and Gleason score ≤7, after radical prostatectomy.


Patients with T2 prostate cancer have disease that is clinically evident and is organ confined; patients with T3 tumors have disease that has penetrated the prostatic capsule and/or has invaded the seminal vesicles. It is known from surgical series that clinical staging underestimates pathological stage, so that about 20% of patients who are clinically T2 will be pT3 after prostatectomy. Most of patients with T2 or T3 prostate cancer are treated with local therapy, either prostatectomy or radiation. The data from the Scandinavian trial suggest that for T2 patients with Gleason grade ≤7, the effect of prostatectomy on survival is at most 5% at 10 years; the majority of patients do not benefit from surgical treatment at the time of diagnosis. For T2 patients with Gleason >7 or for T3 patients, the treatment effect of prostatectomy is assumed to be significant but has not been determined in randomized trials. It is known that these patients have a significant risk (10-30%) of recurrence at 10 years after local treatment, however, there are no prospective randomized trials that define the optimal local treatment (radical prostatectomy, radiation) at diagnosis, which patients are likely to benefit from neo-adjuvant/adjuvant androgen deprivation therapy, and whether treatment (androgen deprivation, chemotherapy) at the time of biochemical failure (elevated PSA) has any clinical benefit.


Accurately determining Gleason scores from needle biopsies presents several technical challenges. First, interpreting histology that is “borderline” between Gleason pattern is highly subjective, even for urologic pathologists. Second, incomplete biopsy sampling is yet another reason why the “predicted” Gleason score on biopsy does not always correlate with the actual “observed” Gleason score of the prostate cancer in the gland itself. Hence, the accuracy of Gleason scoring is dependent upon not only the expertise of the pathologist reading the slides, but also on the completeness and adequacy of the prostate biopsy sampling strategy. T. Stamey, Urology 45:2-12 (1995). The gene/microRNA expression assay and associated information provided by the practice of the methods disclosed herein provide a molecular assay method to facilitate optimal treatment decision-making in early stage prostate cancer. An exemplary embodiment provides genes and microRNAs, the expression levels of which are associated (positively or negatively) with prostate cancer recurrence. For example, such a clinical tool would enable physicians to identify T2/T3 patients who are likely to recur following definitive therapy and need adjuvant treatment.


In addition, the methods disclosed herein may allow physicians to classify tumors, at a molecular level, based on expression level(s) of one or more genes and/or microRNAs that are significantly associated with prognostic factors, such as Gleason pattern and TMPRSS fusion status. These methods would not be impacted by the technical difficulties of intra-patient variability, histologically determining Gleason pattern in biopsy samples, or inclusion of histologically normal appearing tissue adjacent to tumor tissue. Multi-analyte gene/microRNA expression tests can be used to measure the expression level of one or more genes and/or microRNAs involved in each of several relevant physiologic processes or component cellular characteristics. The methods disclosed herein may group the genes and/or microRNAs. The grouping of genes and microRNAs may be performed at least in part based on knowledge of the contribution of those genes and/or microRNAs according to physiologic functions or component cellular characteristics, such as in the groups discussed above. Furthermore, one or more microRNAs may be combined with one or moregenes. The gene-microRNA combination may be selected based on the likelihood that the gene-microRNA combination functionally interact. The formation of groups (or gene subsets), in addition, can facilitate the mathematical weighting of the contribution of various expression levels to cancer recurrence. The weighting of a gene/microRNA group representing a physiological process or component cellular characteristic can reflect the contribution of that process or characteristic to the pathology of the cancer and clinical outcome.


Optionally, the methods disclosed may be used to classify patients by risk, for example risk of recurrence. Patients can be partitioned into subgroups (e.g., tertiles or quartiles) and the values chosen will define subgroups of patients with respectively greater or lesser risk.


The utility of a disclosed gene marker in predicting prognosis may not be unique to that marker. An alternative marker having an expression pattern that is parallel to that of a disclosed gene may be substituted for, or used in addition to, that co-expressed gene or microRNA. Due to the co-expression of such genes or microRNAs, substitution of expression level values should have little impact on the overall utility of the test. The closely similar expression patterns of two genes or microRNAs may result from involvement of both genes or microRNAs in the same process and/or being under common regulatory control in prostate tumor cells. The present disclosure thus contemplates the use of such co-expressed genes, gene subsets, or microRNAs as substitutes for, or in addition to, genes of the present disclosure.


Methods of Assaying Expression Levels of a Gene Product

The methods and compositions of the present disclosure will employ, unless otherwise indicated, conventional techniques of molecular biology (including recombinant techniques), microbiology, cell biology, and biochemistry, which are within the skill of the art. Exemplary techniques are explained fully in the literature, such as, “Molecular Cloning: A Laboratory Manual”, 2nd edition (Sambrook et al., 1989); “Oligonucleotide Synthesis” (M. J. Gait, ed., 1984); “Animal Cell Culture” (R. I. Freshney, ed., 1987); “Methods in Enzymology” (Academic Press, Inc.); “Handbook of Experimental Immunology”, 4th edition (D. M. Weir & C. C. Blackwell, eds., Blackwell Science Inc., 1987); “Gene Transfer Vectors for Mammalian Cells” (J. M. Miller & M. P. Calos, eds., 1987); “Current Protocols in Molecular Biology” (F. M. Ausubel et al., eds., 1987); and “PCR: The Polymerase Chain Reaction”, (Mullis et al., eds., 1994).


Methods of gene expression profiling include methods based on hybridization analysis of polynucleotides, methods based on sequencing of polynucleotides, and proteomics-based methods. Exemplary methods known in the art for the quantification of RNA expression in a sample include northern blotting and in situ hybridization (Parker & Barnes, Methods in Molecular Biology 106:247-283 (1999)); RNAse protection assays (Hod, Biotechniques 13:852-854 (1992)); and PCR-based methods, such as reverse transcription PCT (RT-PCR) (Weis et al., Trends in Genetics 8:263-264 (1992)). Antibodies may be employed that can recognize sequence-specific duplexes, including DNA duplexes, RNA duplexes, and DNA-RNA hybrid duplexes or DNA-protein duplexes. Representative methods for sequencing-based gene expression analysis include Serial Analysis of Gene Expression (SAGE), and gene expression analysis by massively parallel signature sequencing (MPSS).


Reverse Transcriptase PCR (RT-PCR)


Typically, mRNA or microRNA is isolated from a test sample. The starting material is typically total RNA isolated from a human tumor, usually from a primary tumor. Optionally, normal tissues from the same patient can be used as an internal control. Such normal tissue can be histologically-appearing normal tissue adjacent a tumor. mRNA or microRNA can be extracted from a tissue sample, e.g., from a sample that is fresh, frozen (e.g. fresh frozen), or paraffin-embedded and fixed (e.g. formalin-fixed).


General methods for mRNA and microRNA extraction are well known in the art and are disclosed in standard textbooks of molecular biology, including Ausubel et al., Current Protocols of Molecular Biology, John Wiley and Sons (1997). Methods for RNA extraction from paraffin embedded tissues are disclosed, for example, in Rupp and Locker, Lab Invest. 56:A67 (1987), and De Andres et al., BioTechniques 18:42044 (1995). In particular, RNA isolation can be performed using a purification kit, buffer set and protease from commercial manufacturers, such as Qiagen, according to the manufacturer's instructions. For example, total RNA from cells in culture can be isolated using Qiagen RNeasy mini-columns. Other commercially available RNA isolation kits include MasterPure™ Complete DNA and RNA Purification Kit (EPICENTRE®, Madison, Wis.), and Paraffin Block RNA Isolation Kit (Ambion, Inc.). Total RNA from tissue samples can be isolated using RNA Stat-60 (Tel-Test). RNA prepared from tumor can be isolated, for example, by cesium chloride density gradient centrifugation.


The sample containing the RNA is then subjected to reverse transcription to produce cDNA from the RNA template, followed by exponential amplification in a PCR reaction. The two most commonly used reverse transcriptases are avilo myeloblastosis virus reverse transcriptase (AMV-RT) and Moloney murine leukemia virus reverse transcriptase (MMLV-RT). The reverse transcription step is typically primed using specific primers, random hexamers, or oligo-dT primers, depending on the circumstances and the goal of expression profiling. For example, extracted RNA can be reverse-transcribed using a GeneAmp RNA PCR kit (Perkin Elmer, CA, USA), following the manufacturer's instructions. The derived cDNA can then be used as a template in the subsequent PCR reaction.


PCR-based methods use a thermostable DNA-dependent DNA polymerase, such as a Taq DNA polymerase. For example, TaqMan® PCR typically utilizes the 5′-nuclease activity of Taq or Tth polymerase to hydrolyze a hybridization probe bound to its target amplicon, but any enzyme with equivalent 5′ nuclease activity can be used. Two oligonucleotide primers are used to generate an amplicon typical of a PCR reaction product. A third oligonucleotide, or probe, can be designed to facilitate detection of a nucleotide sequence of the amplicon located between the hybridization sites the two PCR primers. The probe can be detectably labeled, e.g., with a reporter dye, and can further be provided with both a fluorescent dye, and a quencher fluorescent dye, as in a Taqman® probe configuration. Where a Taqman® probe is used, during the amplification reaction, the Taq DNA polymerase enzyme cleaves the probe in a template-dependent manner. The resultant probe fragments disassociate in solution, and signal from the released reporter dye is free from the quenching effect of the second fluorophore. One molecule of reporter dye is liberated for each new molecule synthesized, and detection of the unquenched reporter dye provides the basis for quantitative interpretation of the data.


TaqMan® RT-PCR can be performed using commercially available equipment, such as, for example, high-throughput platforms such as the ABI PRISM 7700 Sequence Detection System® (Perkin-Elmer-Applied Biosystems, Foster City, Calif., USA), or Lightcycler (Roche Molecular Biochemicals, Mannheim, Germany). In a preferred embodiment, the procedure is run on a LightCycler® 480 (Roche Diagnostics) real-time PCR system, which is a microwell plate-based cycler platform.


5′-Nuclease assay data are commonly initially expressed as a threshold cycle (“CT”). Fluorescence values are recorded during every cycle and represent the amount of product amplified to that point in the amplification reaction. The threshold cycle (CT) is generally described as the point when the fluorescent signal is first recorded as statistically significant. Alternatively, data may be expressed as a crossing point (“Cp”). The Cp value is calculated by determining the second derivatives of entire qPCR amplification curves and their maximum value. The Cp value represents the cycle at which the increase of fluorescence is highest and where the logarithmic phase of a PCR begins.


To minimize errors and the effect of sample-to-sample variation, RT-PCR is usually performed using an internal standard. The ideal internal standard gene (also referred to as a reference gene) is expressed at a quite constant level among cancerous and non-cancerous tissue of the same origin (i.e., a level that is not significantly different among normal and cancerous tissues), and is not significantly affected by the experimental treatment (i.e., does not exhibit a significant difference in expression level in the relevant tissue as a result of exposure to chemotherapy), and expressed at a quite constant level among the same tissue taken from different patients. For example, reference genes useful in the methods disclosed herein should not exhibit significantly different expression levels in cancerous prostate as compared to normal prostate tissue. RNAs frequently used to normalize patterns of gene expression are mRNAs for the housekeeping genes glyceraldehyde-3-phosphate-dehydrogenase (GAPDH) and (3-actin. Exemplary reference genes used for normalization comprise one or more of the following genes: AAMP, ARF1, ATP5E, CLTC, GPS1, and PGK1. Gene expression measurements can be normalized relative to the mean of one or more (e.g., 2, 3, 4, 5, or more) reference genes. Reference-normalized expression measurements can range from 2 to 15, where a one unit increase generally reflects a 2-fold increase in RNA quantity.


Real time PCR is compatible both with quantitative competitive PCR, where internal competitor for each target sequence is used for normalization, and with quantitative comparative PCR using a normalization gene contained within the sample, or a housekeeping gene for RT-PCR. For further details see, e.g. Held et al., Genome Research 6:986-994 (1996).


The steps of a representative protocol for use in the methods of the present disclosure use fixed, paraffin-embedded tissues as the RNA source. For example, mRNA isolation, purification, primer extension and amplification can be performed according to methods available in the art. (see, e.g., Godfrey et al. J. Molec. Diagnostics 2: 84-91 (2000); Specht et al., Am. J. Pathol. 158: 419-29 (2001)). Briefly, a representative process starts with cutting about 10 μm thick sections of paraffin-embedded tumor tissue samples. The RNA is then extracted, and protein and DNA depleted from the RNA-containing sample. After analysis of the RNA concentration, RNA is reverse transcribed using gene specific primers followed by RT-PCR to provide for cDNA amplification products.


Design of Intron-Based PCR Primers and Probes


PCR primers and probes can be designed based upon exon or intron sequences present in the mRNA transcript of the gene of interest. Primer/probe design can be performed using publicly available software, such as the DNA BLAT software developed by Kent, W. J., Genome Res. 12(4):656-64 (2002), or by the BLAST software including its variations.


Where necessary or desired, repetitive sequences of the target sequence can be masked to mitigate non-specific signals. Exemplary tools to accomplish this include the Repeat Masker program available on-line through the Baylor College of Medicine, which screens DNA sequences against a library of repetitive elements and returns a query sequence in which the repetitive elements are masked. The masked intron sequences can then be used to design primer and probe sequences using any commercially or otherwise publicly available primer/probe design packages, such as Primer Express (Applied Biosystems); MGB assay-by-design (Applied Biosystems); Primer3 (Steve Rozen and Helen J. Skaletsky (2000) Primer3 on the WWW for general users and for biologist programmers. See S. Rrawetz, S. Misener, Bioinformatics Methods and Protocols: Methods in Molecular Biology, pp. 365-386 (Humana Press).


Other factors that can influence PCR primer design include primer length, melting temperature (Tm), and G/C content, specificity, complementary primer sequences, and 3′-end sequence. In general, optimal PCR primers are generally 17-30 bases in length, and contain about 20-80%, such as, for example, about 50-60% G+C bases, and exhibit Tm's between 50 and 80° C., e.g. about 50 to 70° C.


For further guidelines for PCR primer and probe design see, e.g. Dieffenbach, C W. et al, “General Concepts for PCR Primer Design” in: PCR Primer, A Laboratory Manual, Cold Spring Harbor Laboratory Press, New York, 1995, pp. 133-155; Innis and Gelfand, “Optimization of PCRs” in: PCR Protocols, A Guide to Methods and Applications, CRC Press, London, 1994, pp. 5-11; and Plasterer, T.N. Primerselect: Primer and probe design. Methods Mol. Biol. 70:520-527 (1997), the entire disclosures of which are hereby expressly incorporated by reference.


Table A provides further information concerning the primer, probe, and amplicon sequences associated with the Examples disclosed herein.


MassARRAY® System


In MassARRAY-based methods, such as the exemplary method developed by Sequenom, Inc. (San Diego, Calif.) following the isolation of RNA and reverse transcription, the obtained cDNA is spiked with a synthetic DNA molecule (competitor), which matches the targeted cDNA region in all positions, except a single base, and serves as an internal standard. The cDNA/competitor mixture is PCR amplified and is subjected to a post-PCR shrimp alkaline phosphatase (SAP) enzyme treatment, which results in the dephosphorylation of the remaining nucleotides. After inactivarion of the alkaline phosphatase, the PCR products from the competitor and cDNA are subjected to primer extension, which generates distinct mass signals for the competitor- and cDNA-derives PCR products. After purification, these products are dispensed on a chip array, which is pre-loaded with components needed for analysis with matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis. The cDNA present in the reaction is then quantified by analyzing the ratios of the peak areas in the mass spectrum generated. For further details see, e.g. Ding and Cantor, Proc. Natl. Acad. Sci. USA 100:3059-3064 (2003).


Other PCR-Based Methods


Further PCR-based techniques that can find use in the methods disclosed herein include, for example, BeadArray® technology (Illumina, San Diego, Calif.; Oliphant et al., Discovery of Markers for Disease (Supplement to Biotechniques), June 2002; Ferguson et al., Analytical Chemistry 72:5618 (2000)); BeadsArray for Detection of Gene Expression® (BADGE), using the commercially available LuminexlOO LabMAP® system and multiple color-coded microspheres (Luminex Corp., Austin, Tex.) in a rapid assay for gene expression (Yang et al., Genome Res. 11:1888-1898 (2001)); and high coverage expression profiling (HiCEP) analysis (Fukumura et al., Nucl. Acids. Res. 31(16) e94 (2003).


Microarrays


Expression levels of a gene or microArray of interest can also be assessed using the microarray technique. In this method, polynucleotide sequences of interest (including cDNAs and oligonucleotides) are arrayed on a substrate. The arrayed sequences are then contacted under conditions suitable for specific hybridization with detectably labeled cDNA generated from RNA of a test sample. As in the RT-PCR method, the source of RNA typically is total RNA isolated from a tumor sample, and optionally from normal tissue of the same patient as an internal control or cell lines. RNA can be extracted, for example, from frozen or archived paraffin-embedded and fixed (e.g. formalin-fixed) tissue samples.


For example, PCR amplified inserts of cDNA clones of a gene to be assayed are applied to a substrate in a dense array. Usually at least 10,000 nucleotide sequences are applied to the substrate. For example, the microarrayed genes, immobilized on the microchip at 10,000 elements each, are suitable for hybridization under stringent conditions. Fluorescently labeled cDNA probes may be generated through incorporation of fluorescent nucleotides by reverse transcription of RNA extracted from tissues of interest. Labeled cDNA probes applied to the chip hybridize with specificity to each spot of DNA on the array. After washing under stringent conditions to remove non-specifically bound probes, the chip is scanned by confocal laser microscopy or by another detection method, such as a CCD camera. Quantitation of hybridization of each arrayed element allows for assessment of corresponding RNA abundance.


With dual color fluorescence, separately labeled cDNA probes generated from two sources of RNA are hybridized pair wise to the array. The relative abundance of the transcripts from the two sources corresponding to each specified gene is thus determined simultaneously. The miniaturized scale of the hybridization affords a convenient and rapid evaluation of the expression pattern for large numbers of genes. Such methods have been shown to have the sensitivity required to detect rare transcripts, which are expressed at a few copies per cell, and to reproducibly detect at least approximately two-fold differences in the expression levels (Schena et at, Proc. Natl. Acad. ScL USA 93(2):106-149 (1996)). Microarray analysis can be performed by commercially available equipment, following manufacturer's protocols, such as by using the Affymetrix GenChip® technology, or Incyte's microarray technology.


Serial Analysis of Gene Expression (SAGE)


Serial analysis of gene expression (SAGE) is a method that allows the simultaneous and quantitative analysis of a large number of gene transcripts, without the need of providing an individual hybridization probe for each transcript. First, a short sequence tag (about 10-14 bp) is generated that contains sufficient information to uniquely identify a transcript, provided that the tag is obtained from a unique position within each transcript. Then, many transcripts are linked together to form long serial molecules, that can be sequenced, revealing the identity of the multiple tags simultaneously. The expression pattern of any population of transcripts can be quantitatively evaluated by determining the abundance of individual tags, and identifying the gene corresponding to each tag. For more details see, e.g. Velculescu et al., Science 270:484-487 (1995); and Velculescu et al., Cell 88:243-51 (1997).


Gene Expression Analysis by Nucleic Acid Sequencing


Nucleic acid sequencing technologies are suitable methods for analysis of gene expression. The principle underlying these methods is that the number of times a cDNA sequence is detected in a sample is directly related to the relative expression of the RNA corresponding to that sequence. These methods are sometimes referred to by the term Digital Gene Expression (DGE) to reflect the discrete numeric property of the resulting data. Early methods applying this principle were Serial Analysis of Gene Expression (SAGE) and Massively Parallel Signature Sequencing (MPSS). See, e.g., S. Brenner, et al., Nature Biotechnology 18(6):630-634 (2000). More recently, the advent of “next-generation” sequencing technologies has made DGE simpler, higher throughput, and more affordable. As a result, more laboratories are able to utilize DGE to screen the expression of more genes in more individual patient samples than previously possible. See, e.g., J. Marioni, Genome Research 18(9):1509-1517 (2008); R. Morin, Genome Research 18(4):610-621 (2008); A. Mortazavi, Nature Methods 5(7):621-628 (2008); N. Cloonan, Nature Methods 5(7):613-619 (2008).


Isolating RNA from Body Fluids


Methods of isolating RNA for expression analysis from blood, plasma and serum (see, e.g., K. Enders, et al., Clin Chem 48, 1647-53 (2002) (and references cited therein) and from urine (see, e.g., R. Boom, et al., J Clin Microbiol. 28, 495-503 (1990) and references cited therein) have been described.


Immunohistochemistry


Immunohistochemistry methods are also suitable for detecting the expression levels of genes and applied to the method disclosed herein. Antibodies (e.g., monoclonal antibodies) that specifically bind a gene product of a gene of interest can be used in such methods. The antibodies can be detected by direct labeling of the antibodies themselves, for example, with radioactive labels, fluorescent labels, hapten' labels such as, biotin, or an enzyme such as horse radish peroxidase or alkaline phosphatase. Alternatively, unlabeled primary antibody can be used in conjunction with a labeled secondary antibody specific for the primary antibody. Immunohistochemistry protocols and kits are well known in the art and are commercially available.


Proteomics


The term “proteome” is defined as the totality of the proteins present in a sample (e.g. tissue, organism, or cell culture) at a certain point of time. Proteomics includes, among other things, study of the global changes of protein expression in a sample (also referred to as “expression proteomics”). Proteomics typically includes the following steps: (1) separation of individual proteins in a sample by 2-D gel electrophoresis (2-D PAGE); (2) identification of the individual proteins recovered from the gel, e.g. my mass spectrometry or N-terminal sequencing, and (3) analysis of the data using bioinformatics.


General Description of the mRNA/microRNA Isolation, Purification and Amplification


The steps of a representative protocol for profiling gene expression using fixed, paraffin-embedded tissues as the RNA source, including mRNA or microRNA isolation, purification, primer extension and amplification are provided in various published journal articles. (See, e.g., T. E. Godfrey, et al, J. Molec. Diagnostics 2: 84-91 (2000); K. Specht et al., Am. J. Pathol. 158: 419-29 (2001), M. Cronin, et al., Am J Pathol 164:35-42 (2004)). Briefly, a representative process starts with cutting a tissue sample section (e.g. about 10 μm thick sections of a paraffin-embedded tumor tissue sample). The RNA is then extracted, and protein and DNA are removed. After analysis of the RNA concentration, RNA repair is performed if desired. The sample can then be subjected to analysis, e.g., by reverse transcribed using gene specific promoters followed by RT-PCR.


Statistical Analysis of Expression Levels in Identification of Genes and MicroRNAs

One skilled in the art will recognize that there are many statistical methods that may be used to determine whether there is a significant relationship between a parameter of interest (e.g., recurrence) and expression levels of a marker gene/microRNA as described here. In an exemplary embodiment, the present invention provides a stratified cohort sampling design (a form of case-control sampling) using tissue and data from prostate cancer patients. Selection of specimens was stratified by T stage (T1, T2), year cohort (<1993, ≥1993), and prostatectomy Gleason Score (low/intermediate, high). All patients with clinical recurrence were selected and a sample of patients who did not experience a clinical recurrence was selected. For each patient, up to two enriched tumor specimens and one normal-appearing tissue sample was assayed.


All hypothesis tests were reported using two-sided p-values. To investigate if there is a significant relationship of outcomes (clinical recurrence-free interval (cRFI), biochemical recurrence-free interval (bRFI), prostate cancer-specific survival (PCSS), and overall survival (OS)) with individual genes and/or microRNAs, demographic or clinical covariates Cox Proportional Hazards (PH) models using maximum weighted pseudo partial-likelihood estimators were used and p-values from Wald tests of the null hypothesis that the hazard ratio (HR) is one are reported. To investigate if there is a significant relationship between individual genes and/or microRNAs and Gleason pattern of a particular sample, ordinal logistic regression models using maximum weighted likelihood methods were used and p-values from Wald tests of the null hypothesis that the odds ratio (OR) is one are reported.


Coexpression Analysis

The present disclosure provides a method to determine tumor stage based on the expression of staging genes, or genes that co-express with particular staging genes. To perform particular biological processes, genes often work together in a concerted way, i.e. they are co-expressed. Co-expressed gene groups identified for a disease process like cancer can serve as biomarkers for tumor status and disease progression. Such co-expressed genes can be assayed in lieu of, or in addition to, assaying of the staging gene with which they are co-expressed.


In an exemplary embodiment, the joint correlation of gene expression levels among prostate cancer specimens under study may be assessed. For this purpose, the correlation structures among genes and specimens may be examined through hierarchical cluster methods. This information may be used to confirm that genes that are known to be highly correlated in prostate cancer specimens cluster together as expected. Only genes exhibiting a nominally significant (unadjusted p<0.05) relationship with cRFI in the univariate Cox PH regression analysis will be included in these analyses.


One skilled in the art will recognize that many co-expression analysis methods now known or later developed will fall within the scope and spirit of the present invention. These methods may incorporate, for example, correlation coefficients, co-expression network analysis, clique analysis, etc., and may be based on expression data from RT-PCR, microarrays, sequencing, and other similar technologies. For example, gene expression clusters can be identified using pair-wise analysis of correlation based on Pearson or Spearman correlation coefficients. (See, e.g., Pearson K. and Lee A., Biometrika 2, 357 (1902); C. Spearman, Amer. J. Psychol 15:72-101 (1904); J. Myers, A. Well, Research Design and Statistical Analysis, p. 508 (2nd Ed., 2003).)


Normalization of Expression Levels

The expression data used in the methods disclosed herein can be normalized. Normalization refers to a process to correct for (normalize away), for example, differences in the amount of RNA assayed and variability in the quality of the RNA used, to remove unwanted sources of systematic variation in Ct or Cp measurements, and the like. With respect to RT-PCR experiments involving archived fixed paraffin embedded tissue samples, sources of systematic variation are known to include the degree of RNA degradation relative to the age of the patient sample and the type of fixative used to store the sample. Other sources of systematic variation are attributable to laboratory processing conditions.


Assays can provide for normalization by incorporating the expression of certain normalizing genes, which do not significantly differ in expression levels under the relevant conditions. Exemplary normalization genes disclosed herein include housekeeping genes. (See, e.g., E. Eisenberg, et al., Trends in Genetics 19(7):362-365 (2003).) Normalization can be based on the mean or median signal (Ct or Cp) of all of the assayed genes or a large subset thereof (global normalization approach). In general, the normalizing genes, also referred to as reference genes should be genes that are known not to exhibit significantly different expression in prostate cancer as compared to non-cancerous prostate tissue, and are not significantly affected by various sample and process conditions, thus provide for normalizing away extraneous effects.


In exemplary embodiments, one or more of the following genes are used as references by which the mRNA or microRNA expression data is normalized: AAMP, ARF1, ATP5E, CLTC, GPS1, and PGK1. In another exemplary embodiment, one or more of the following microRNAs are used as references by which the expression data of microRNAs are normalized: hsa-miR-106a; hsa-miR-146b-5p; hsa-miR-191; hsa-miR-19b; and hsa-miR-92a. The calibrated weighted average CT or Cp measurements for each of the prognostic and predictive genes or microRNAs may be normalized relative to the mean of five or more reference genes or microRNAs.


Those skilled in the art will recognize that normalization may be achieved in numerous ways, and the techniques described above are intended only to be exemplary, not exhaustive.


Standardization of Expression Levels

The expression data used in the methods disclosed herein can be standardized. Standardization refers to a process to effectively put all the genes or microRNAs on a comparable scale. This is performed because some genes or microRNAs will exhibit more variation (a broader range of expression) than others. Standardization is performed by dividing each expression value by its standard deviation across all samples for that gene or microRNA. Hazard ratios are then interpreted as the relative risk of recurrence per 1 standard deviation increase in expression.


Kits of the Invention

The materials for use in the methods of the present invention are suited for preparation of kits produced in accordance with well-known procedures. The present disclosure thus provides kits comprising agents, which may include gene (or microRNA)-specific or gene (or microRNA)-selective probes and/or primers, for quantifying the expression of the disclosed genes or microRNAs for predicting prognostic outcome or response to treatment. Such kits may optionally contain reagents for the extraction of RNA from tumor samples, in particular fixed paraffin-embedded tissue samples and/or reagents for RNA amplification. In addition, the kits may optionally comprise the reagent(s) with an identifying description or label or instructions relating to their use in the methods of the present invention. The kits may comprise containers (including microliter plates suitable for use in an automated implementation of the method), each with one or more of the various materials or reagents (typically in concentrated form) utilized in the methods, including, for example, chromatographic columns, pre-fabricated microarrays, buffers, the appropriate nucleotide triphosphates (e.g., dATP, dCTP, dGTP and dTTP; or rATP, rCTP, rGTP and UTP), reverse transcriptase, DNA polymerase, RNA polymerase, and one or more probes and primers of the present invention (e.g., appropriate length poly(T) or random primers linked to a promoter reactive with the RNA polymerase). Mathematical algorithms used to estimate or quantify prognostic or predictive information are also properly potential components of kits.


Reports

The methods of this invention, when practiced for commercial diagnostic purposes, generally produce a report or summary of information obtained from the herein-described methods. For example, a report may include information concerning expression levels of one or more genes and/or microRNAs, classification of the tumor or the patient's risk of recurrence, the patient's likely prognosis or risk classification, clinical and pathologic factors, and/or other information. The methods and reports of this invention can further include storing the report in a database. The method can create a record in a database for the subject and populate the record with data. The report may be a paper report, an auditory report, or an electronic record. The report may be displayed and/or stored on a computing device (e.g., handheld device, desktop computer, smart device, website, etc.). It is contemplated that the report is provided to a physician and/or the patient. The receiving of the report can further include establishing a network connection to a server computer that includes the data and report and requesting the data and report from the server computer.


Computer Program

The values from the assays described above, such as expression data, can be calculated and stored manually. Alternatively, the above-described steps can be completely or partially performed by a computer program product. The present invention thus provides a computer program product including a computer readable storage medium having a computer program stored on it. The program can, when read by a computer, execute relevant calculations based on values obtained from analysis of one or more biological sample from an individual (e.g., gene expression levels, normalization, standardization, thresholding, and conversion of values from assays to a score and/or text or graphical depiction of tumor stage and related information). The computer program product has stored therein a computer program for performing the calculation.


The present disclosure provides systems for executing the program described above, which system generally includes: a) a central computing environment; b) an input device, operatively connected to the computing environment, to receive patient data, wherein the patient data can include, for example, expression level or other value obtained from an assay using a biological sample from the patient, or microarray data, as described in detail above; c) an output device, connected to the computing environment, to provide information to a user (e.g., medical personnel); and d) an algorithm executed by the central computing environment (e.g., a processor), where the algorithm is executed based on the data received by the input device, and wherein the algorithm calculates an expression score, thresholding, or other functions described herein. The methods provided by the present invention may also be automated in whole or in part.


All aspects of the present invention may also be practiced such that a limited number of additional genes and/or microRNAs that are co-expressed or functionally related with the disclosed genes, for example as evidenced by statistically meaningful Pearson and/or Spearman correlation coefficients, are included in a test in addition to and/or in place of disclosed genes.


Having described the invention, the same will be more readily understood through reference to the following Examples, which are provided by way of illustration, and are not intended to limit the invention in any way.


EXAMPLES
Example 1: RNA Yield and Gene Expression Profiles in Prostate Cancer Biopsy Cores

Clinical tools based on prostate needle core biopsies are needed to guide treatment planning at diagnosis for men with localized prostate cancer. Limiting tissue in needle core biopsy specimens poses significant challenges to the development of molecular diagnostic tests. This study examined RNA extraction yields and gene expression profiles using an RT-PCR assay to characterize RNA from manually micro-dissected fixed paraffin embedded (FPE) prostate cancer needle biopsy cores. It also investigated the association of RNA yields and gene expression profiles with Gleason score in these specimens.


Patients and Samples


This study determined the feasibility of gene expression profile analysis in prostate cancer needle core biopsies by evaluating the quantity and quality of RNA extracted from fixed paraffin-embedded (FPE) prostate cancer needle core biopsy specimens. Forty-eight (48) formalin-fixed blocks from prostate needle core biopsy specimens were used for this study. Classification of specimens was based on interpretation of the Gleason score (2005 Int'l Society of Urological Pathology Consensus Conference) and percentage tumor (<33%, 33-66%, >66%) involvement as assessed by pathologists.









TABLE 1







Distribution of cases










Gleason score
~<33%
~33-66%
~>66%


Category
Tumor
Tumor
Tumor













Low (≤6)
5
5
6


Intermediate (7)
5
5
6


High (8, 9, 10)
5
5
6


Total
15
15
18









Assay Methods


Fourteen (14) serial 5 μm unstained sections from each FPE tissue block were included in the study. The first and last sections for each case were H&E stained and histologically reviewed to confirm the presence of tumor and for tumor enrichment by manual micro-dissection.


RNA from enriched tumor samples was extracted using a manual RNA extraction process. RNA was quantitated using the RiboGreen® assay and tested for the presence of genomic DNA contamination. Samples with sufficient RNA yield and free of genomic DNA tested for gene expression levels of a 24-gene panel of reference and cancer-related genes using quantitative RT-PCR. The expression was normalized to the average of 6 reference genes (AAMP, ARF1, ATP5E, CLTC, EEF1A1, and GPX1).


Statistical Methods


Descriptive statistics and graphical displays were used to summarize standard pathology metrics and gene expression, with stratification for Gleason Score category and percentage tumor involvement category. Ordinal logistic regression was used to evaluate the relationship between gene expression and Gleason Score category.


Results


The RNA yield per unit surface area ranged from 16 to 2406 ng/mm2. Higher RNA yield was observed in samples with higher percent tumor involvement (p=0.02) and higher Gleason score (p=0.01). RNA yield was sufficient (>200 ng) in 71% of cases to permit 96-well RT-PCR, with 87% of cases having >100 ng RNA yield. The study confirmed that gene expression from prostate biopsies, as measured by qRT-PCR, was comparable to FPET samples used in commercial molecular assays for breast cancer. In addition, it was observed that greater biopsy RNA yields are found with higher Gleason score and higher percent tumor involvement. Nine genes were identified as significantly associated with Gleason score (p<0.05) and there was a large dynamic range observed for many test genes.


Example 2: Gene Expression Analysis for Genes Associated with Prognosis in Prostate Cancer

Patients and Samples


Approximately 2600 patients with clinical stage T1/T2 prostate cancer treated with radical prostatectomy (RP) at the Cleveland Clinic between 1987 and 2004 were identified. Patients were excluded from the study design if they received neo-adjuvant and/or adjuvant therapy, if pre-surgical PSA levels were missing, or if no tumor block was available from initial diagnosis. 127 patients with clinical recurrence and 374 patients without clinical recurrence after radical prostatectomy were randomly selected using a cohort sampling design. The specimens were stratified by T stage (T1, T2), year cohort (<1993, ≥1993), and prostatectomy Gleason score (low/intermediate, high). Of the 501 sampled patients, 51 were excluded for insufficient tumor; 7 were excluded due to clinical ineligibility; 2 were excluded due to poor quality of gene expression data; and 10 were excluded because primary Gleason pattern was unavailable. Thus, this gene expression study included tissue and data from 111 patients with clinical recurrence and 330 patients without clinical recurrence after radical prostatectomies performed between 1987 and 2004 for treatment of early stage (T1, T2) prostate cancer.


Two fixed paraffin embedded (FPE) tissue specimens were obtained from prostate tumor specimens in each patient. The sampling method (sampling method A or B) depended on whether the highest Gleason pattern is also the primary Gleason pattern. For each specimen selected, the invasive cancer cells were at least 5.0 mm in dimension, except in the instances of pattern 5, where 2.2 mm was accepted. Specimens were spatially distinct where possible.









TABLE 2







Sampling Methods








Sampling Method A
Sampling Method B





For patients whose prostatectomy
For patients whose prostatectomy


primary Gleason pattern is also
primary Gleason pattern is not


the highest Gleason pattern
the highest Gleason pattern


Specimen 1 (A1) =
Specimen 1 (B1) =


primary Gleason pattern
highest Gleason pattern


Select and mark largest focus
Select highest Gleason pattern


(greatest cross-sectional area)
tissue from spatially distinct area


of primary Gleason pattern
from specimen B2, if


tissue. Invasive cancer area
possible. Invasive cancer area


≥5.0 mm.
at least 5.0 mm if selecting



secondary pattern, at least



2.2 mm if selecting Gleason



pattern 5.


Specimen 2 (A2) =
Specimen 2 (B2) =


secondary Gleason pattern
primary Gleason pattern


Select and mark secondary
Select largest focus


Gleason pattern tissue from
(greatest cross-sectional area)


spatially distinct area from
of primary Gleason pattern tissue.


specimen A1. Invasive cancer
Invasive cancer area ≥5.0 mm.


area ≥5.0 mm.









Histologically normal appearing tissue (NAT) adjacent to the tumor specimen (also referred to in these Examples as “non-tumor tissue”) was also evaluated. Adjacent tissue was collected 3 mm from the tumor to 3 mm from the edge of the FPET block. NAT was preferentially sampled adjacent to the primary Gleason pattern. In cases where there was insufficient NAT adjacent to the primary Gleason pattern, then NAT was sampled adjacent to the secondary or highest Gleason pattern (A2 or B1) per the method set forth in Table 2. Six (6) 10 μm sections with beginning H&E at 5 μm and ending unstained slide at 5 μm were prepared from each fixed paraffin-embedded tumor (FPET) block included in the study. All cases were histologically reviewed and manually micro-dissected to yield two enriched tumor samples and, where possible, one normal tissue sample adjacent to the tumor specimen.


Assay Method


In this study, RT-PCR analysis was used to determine RNA expression levels for 738 genes and chromosomal rearrangements (e.g., TMPRSS2-ERG fusion or other ETS family genes) in prostate cancer tissue and surrounding NAT in patients with early-stage prostate cancer treated with radical prostatectomy.


The samples were quantified using the RiboGreen assay and a subset tested for presence of genomic DNA contamination. Samples were taken into reverse transcription (RT) and quantitative polymerase chain reaction (qPCR). All analyses were conducted on reference-normalized gene expression levels using the average of the of replicate well crossing point (CP) values for the 6 reference genes (AAMP, ARF1, ATP5E, CLTC, GPS1, PGK1).


Statistical Analysis and Results


Primary statistical analyses involved 111 patients with clinical recurrence and 330 patients without clinical recurrence after radical prostatectomy for early-stage prostate cancer stratified by T-stage (T1, T2), year cohort (<1993, ≥1993), and prostatectomy Gleason score (low/intermediate, high). Gleason score categories are defined as follows: low (Gleason score ≤6), intermediate (Gleason score=7), and high (Gleason score ≥8). A patient was included in a specified analysis if at least one sample for that patient was evaluable. Unless otherwise stated, all hypothesis tests were reported using two-sided p-values. The method of Storey was applied to the resulting set of p-values to control the false discovery rate (FDR) at 20%. J. Storey, R. Tibshirani, Estimating the Positive False Discovery Rate Under Dependence, with Applications to DNA Microarrays, Dept. of Statistics, Stanford Univ. (2001).


Analysis of gene expression and recurrence-free interval was based on univariate Cox Proportional Hazards (PH) models using maximum weighted pseudo-partial-likelihood estimators for each evaluable gene in the gene list (727 test genes and 5 reference genes). P-values were generated using Wald tests of the null hypothesis that the hazard ratio (HR) is one. Both unadjusted p-values and the q-value (smallest FDR at which the hypothesis test in question is rejected) were reported. Un-adjusted p-values <0.05 were considered statistically significant. Since two tumor specimens were selected for each patient, this analysis was performed using the 2 specimens from each patient as follows: (1) analysis using the primary Gleason pattern specimen from each patient (Specimens A1 and B2 as described in Table 2); (2) analysis using the highest Gleason pattern specimen from each patient (Specimens A1 and B1 as described in Table 2).


Analysis of gene expression and Gleason pattern (3, 4, 5) was based on univariate ordinal logistic regression models using weighted maximum likelihood estimators for each gene in the gene list (727 test genes and 5 reference genes). P-values were generated using a Wald test of the null hypothesis that the odds ratio (OR) is one. Both unadjusted p-values and the q-value (smallest FDR at which the hypothesis test in question is rejected) were reported. Un-adjusted p-values <0.05 were considered statistically significant. Since two tumor specimens were selected for each patient, this analysis was performed using the 2 specimens from each patient as follows: (1) analysis using the primary Gleason pattern specimen from each patient (Specimens A1 and B2 as described in Table 2); (2) analysis using the highest Gleason pattern specimen from each patient (Specimens A1 and B1 as described in Table 2).


It was determined whether there is a significant relationship between cRFI and selected demographic, clinical, and pathology variables, including age, race, clinical tumor stage, pathologic tumor stage, location of selected tumor specimens within the prostate (peripheral versus transitional zone), PSA at the time of surgery, overall Gleason score from the radical prostatectomy, year of surgery, and specimen Gleason pattern. Separately for each demographic or clinical variable, the relationship between the clinical covariate and cRFI was modeled using univariate Cox PH regression using weighted pseudo partial-likelihood estimators and a p-value was generated using Wald's test of the null hypothesis that the hazard ratio (HR) is one. Covariates with unadjusted p-values <0.2 may have been included in the covariate-adjusted analyses.


It was determined whether there was a significant relationship between each of the individual cancer-related genes and cRFI after controlling for important demographic and clinical covariates. Separately for each gene, the relationship between gene expression and cRFI was modeled using multivariate Cox PH regression using weighted pseudo partial-likelihood estimators including important demographic and clinical variables as covariates. The independent contribution of gene expression to the prediction of cRFI was tested by generating a p-value from a Wald test using a model that included clinical covariates for each nodule (specimens as defined in Table 2). Un-adjusted p-values <0.05 were considered statistically significant.


Tables 3A and 3B provide genes significantly associated (p<0.05), positively or negatively, with Gleason pattern in the primary and/or highest Gleason pattern. Increased expression of genes in Table 3A is positively associated with higher Gleason score, while increased expression of genes in Table 3B are negatively associated with higher Gleason score.









TABLE 3A







Gene significantly (p < 0.05) associated with Gleason pattern for


all specimens in the primary Gleason pattern or highest Gleason


pattern odds ratio (OR) >1.0 (Increased expression


is positively associated with higher Gleason Score)










Primary Pattern
Highest Pattern











Official Symbol
OR
p-value
OR
p-value














ALCAM
1.73
<.001
1.36
0.009


ANLN
1.35
0.027




APOC1
1.47
0.005
1.61
<.001


APOE
1.87
<.001
2.15
<.001


ASAP2
1.53
0.005




ASPN
2.62
<.001
2.13
<.001


ATP5E
1.35
0.035




AURKA
1.44
0.010




AURKB
1.59
<.001
1.56
<.001


BAX
1.43
0.006




BGN
2.58
<.001
2.82
<.001


BIRC5
1.45
0.003
1.79
<.001


BMP6
2.37
<.001
1.68
<.001


BMPR1B
1.58
0.002




BRCA2


1.45
0.013


BUB1
1.73
<.001
1.57
<.001


CACNA1D
1.31
0.045
1.31
0.033


CADPS


1.30
0.023


CCNB1
1.43
0.023




CCNE2
1.52
0.003
1.32
0.035


CD276
2.20
<.001
1.83
<.001


CD68


1.36
0.022


CDC20
1.69
<.001
1.95
<.001


CDC6
1.38
0.024
1.46
<.001


CDH11


1.30
0.029


CDKN2B
1.55
0.001
1.33
0.023


CDKN2C
1.62
<.001
1.52
<.001


CDKN3
1.39
0.010
1.50
0.002


CENPF
1.96
<.001
1.71
<.001


CHRAC1


1.34
0.022


CLDN3


1.37
0.029


COL1A1
2.23
<.001
2.22
<.001


COL1A2


1.42
0.005


COL3A1
1.90
<.001
2.13
<.001


COL8A1
1.88
<.001
2.35
<.001


CRISP3
1.33
0.040
1.26
0.050


CTHRC1
2.01
<.001
1.61
<.001


CTNND2
1.48
0.007
1.37
0.011


DAPK1
1.44
0.014




DIAPH1
1.34
0.032
1.79
<.001


DIO2


1.56
0.001


DLL4
1.38
0.026
1.53
<.001


ECE1
1.54
0.012
1.40
0.012


ENY2
1.35
0.046
1.35
0.012


EZH2
1.39
0.040




F2R
2.37
<.001
2.60
<.001


FAM49B
1.57
0.002
1.33
0.025


FAP
2.36
<.001
1.89
<.001


FCGR3A
2.10
<.001
1.83
<.001


GNPTAB
1.78
<.001
1.54
<.001


GSK3B


1.39
0.018


HRAS
1.62
0.003




HSD17B4
2.91
<.001
1.57
<.001


HSPA8
1.48
0.012
1.34
0.023


IFI30
1.64
<.001
1.45
0.013


IGFBP3


1.29
0.037


IL11
1.52
0.001
1.31
0.036


INHBA
2.55
<.001
2.30
<.001


ITGA4


1.35
0.028


JAG1
1.68
<.001
1.40
0.005


KCNN2
1.50
0.004




KCTD12


1.38
0.012


KHDRBS3
1.85
<.001
1.72
<.001


KIF4A
1.50
0.010
1.50
<.001


KLK14
1.49
0.001
1.35
<.001


KPNA2
1.68
0.004
1.65
0.001


KRT2


1.33
0.022


KRT75


1.27
0.028


LAMC1
1.44
0.029




LAPTM5
1.36
0.025
1.31
0.042


LTBP2
1.42
0.023
1.66
<.001


MANF


1.34
0.019


MAOA
1.55
0.003
1.50
<.001


MAP3K5
1.55
0.006
1.44
0.001


MDK
1.47
0.013
1.29
0.041


MDM2


1.31
0.026


MELK
1.64
<.001
1.64
<.001


MMP11
2.33
<.001
1.66
<.001


MYBL2
1.41
0.007
1.54
<.001


MYO6


1.32
0.017


NETO2


1.36
0.018


NOX4
1.84
<.001
1.73
<.001


NPM1
1.68
0.001




NRIP3


1.36
0.009


NRP1
1.80
0.001
1.36
0.019


OSM
1.33
0.046




PATE1
1.38
0.032




PECAM1
1.38
0.021
1.31
0.035


PGD
1.56
0.010




PLK1
1.51
0.004
1.49
0.002


PLOD2


1.29
0.027


POSTN
1.70
0.047
1.55
0.006


PPP3CA
1.38
0.037
1.37
0.006


PTK6
1.45
0.007
1.53
<.001


PTTG1


1.51
<.001


RAB31


1.31
0.030


RAD21
2.05
<.001
1.38
0.020


RAD51
1.46
0.002
1.26
0.035


RAF1
1.46
0.017




RALBP1
1.37
0.043




RHOC


1.33
0.021


ROBO2
1.52
0.003
1.41
0.006


RRM2
1.77
<.001
1.50
<.001


SAT1
1.67
0.002
1.61
<.001


SDC1
1.66
0.001
1.46
0.014


SEC14L1
1.53
0.003
1.62
<.001


SESN3
1.76
<.001
1.45
<.001


SFRP4
2.69
<.001
2.03
<.001


SHMT2
1.69
0.007
1.45
0.003


SKIL


1.46
0.005


SOX4
1.42
0.016
1.27
0.031


SPARC
1.40
0.024
1.55
<.001


SPINK1


1.29
0.002


SPP1
1.51
0.002
1.80
<.001


TFDP1
1.48
0.014




THBS2
1.87
<.001
1.65
<.001


THY1
1.58
0.003
1.64
<.001


TK1
1.79
<.001
1.42
0.001


TOP2A
2.30
<.001
2.01
<.001


TPD52
1.95
<.001
1.30
0.037


TPX2
2.12
<.001
1.86
<.001


TYMP
1.36
0.020




TYMS
1.39
0.012
1.31
0.036


UBE2C
1.66
<.001
1.65
<.001


UBE2T
1.59
<.001
1.33
0.017


UGDH


1.28
0.049


UGT2B15
1.46
0.001
1.25
0.045


UHRF1
1.95
<.001
1.62
<.001


VDR
1.43
0.010
1.39
0.018


WNT5A
1.54
0.001
1.44
0.013
















TABLE 3B







Gene significantly (p < 0.05) associated with Gleason pattern for all


specimens in the primary Gleason pattern or highest Gleason pattern


odds ratio (OR) < 1.0 (Increased expression is negatively associated


with higher Gleason score)









Table 3B
Primary Pattern
Highest Pattern











Official Symbol
OR
p-value
OR
p-value





ABCA5
0.78
0.041




ABCG2
0.65
0.001
0.72
0.012


ACOX2
0.44
<.001
0.53
<.001


ADH5
0.45
<.001
0.42
<.001


AFAP1


0.79
0.038


AIG1


0.77
0.024


AKAP1
0.63
0.002




AKR1C1
0.66
0.003
0.63
<.001


AKT3
0.68
0.006
0.77
0.010


ALDH1A2
0.28
<.001
0.33
<.001


ALKBH3
0.77
0.040
0.77
0.029


AMPD3
0.67
0.007




ANPEP
0.68
0.008
0.59
<.001


ANXA2
0.72
0.018




APC


0.69
0.002


AXIN2
0.46
<.001
0.54
<.001


AZGP1
0.52
<.001
0.53
<.001


BIK
0.69
0.006
0.73
0.003


BIN1
0.43
<.001
0.61
<.001


BTG3


0.79
0.030


BTRC
0.48
<.001
0.62
<.001


C7
0.37
<.001
0.55
<.001


CADM1
0.56
<.001
0.69
0.001


CAV1
0.58
0.002
0.70
0.009


CAV2
0.65
0.029




CCNH
0.67
0.006
0.77
0.048


CD164
0.59
0.003
0.57
<.001


CDC25B
0.77
0.035




CDH1


0.66
<.001


CDK2


0.71
0.003


CDKN1C
0.58
<.001
0.57
<.001


CDS2


0.69
0.002


CHN1
0.66
0.002




COL6A1
0.44
<.001
0.66
<.001


COL6A3
0.66
0.006




CSRP1
0.42
0.006




CTGF
0.74
0.043




CTNNA1
0.70
<.001
0.83
0.018


CTNNB1
0.70
0.019




CTNND1


0.75
0.028


CUL1


0.74
0.011


CXCL12
0.54
<.001
0.74
0.006


CYP3A5
0.52
<.001
0.66
0.003


CYR61
0.64
0.004
0.68
0.005


DDR2
0.57
0.002
0.73
0.004


DES
0.34
<.001
0.58
<.001


DLGAP1
0.54
<.001
0.62
<.001


DNM3
0.67
0.004




DPP4
0.41
<.001
0.53
<.001


DPT
0.28
<.001
0.48
<.001


DUSP1
0.59
<.001
0.63
<.001


EDNRA
0.64
0.004
0.74
0.008


EGF


0.71
0.012


EGR1
0.59
<.001
0.67
0.009


EGR3
0.72
0.026
0.71
0.025


EIF5


0.76
0.025


ELK4
0.58
0.001
0.70
0.008


ENPP2
0.66
0.002
0.70
0.005


EPHA3
0.65
0.006




EPHB2
0.60
<.001
0.78
0.023


EPHB4
0.75
0.046
0.73
0.006


ERBB3
0.76
0.040
0.75
0.013


ERBB4


0.74
0.023


ERCC1
0.63
<.001
0.77
0.016


FAAH
0.67
0.003
0.71
0.010


FAM107A
0.35
<.001
0.59
<.001


FAM13C
0.37
<.001
0.48
<.001


FAS
0.73
0.019
0.72
0.008


FGF10
0.53
<.001
0.58
<.001


FGF7
0.52
<.001
0.59
<.001


FGFR2
0.60
<.001
0.59
<.001


FKBP5
0.70
0.039
0.68
0.003


FLNA
0.39
<.001
0.56
<.001


FLNC
0.33
<.001
0.52
<.001


FOS
0.58
<.001
0.66
0.005


FOXO1
0.57
<.001
0.67
<.001


FOXQ1


0.74
0.023


GADD45B
0.62
0.002
0.71
0.010


GHR
0.62
0.002
0.72
0.009


GNRH1
0.74
0.049
0.75
0.026


GPM6B
0.48
<.001
0.68
<.001


GPS1


0.68
0.003


GSN
0.46
<.001
0.77
0.027


GSTM1
0.44
<.001
0.62
<.001


GSTM2
0.29
<.001
0.49
<.001


HGD


0.77
0.020


HIRIP3
0.75
0.034




HK1
0.48
<.001
0.66
0.001


HLF
0.42
<.001
0.55
<.001


HNF1B
0.67
0.006
0.74
0.010


HPS1
0.66
0.001
0.65
<.001


HSP90AB1
0.75
0.042




HSPA5
0.70
0.011




HSPB2
0.52
<.001
0.70
0.004


IGF1
0.35
<.001
0.59
<.001


IGF2
0.48
<.001
0.70
0.005


IGFBP2
0.61
<.001
0.77
0.044


IGFBP5
0.63
<.001




IGFBP6
0.45
<.001
0.64
<.001


IL6ST
0.55
0.004
0.63
<.001


ILK
0.40
<.001
0.57
<.001


ING5
0.56
<.001
0.78
0.033


ITGA1
0.56
0.004
0.61
<.001


ITGA3


0.78
0.035


ITGA5
0.71
0.019
0.75
0.017


ITGA7
0.37
<.001
0.52
<.001


ITGB3
0.63
0.003
0.70
0.005


ITPR1
0.46
<.001
0.64
<.001


ITPR3
0.70
0.013




ITSN1
0.62
0.001




JUN
0.48
<.001
0.60
<.001


JUNB
0.72
0.025




KIT
0.51
<.001
0.68
0.007


KLC1
0.58
<.001




KLK1
0.69
0.028
0.66
0.003


KLK2
0.60
<.001




KLK3
0.63
<.001
0.69
0.012


KRT15
0.56
<.001
0.60
<.001


KRT18
0.74
0.034




KRT5
0.64
<.001
0.62
<.001


LAMA4
0.47
<.001
0.73
0.010


LAMB3
0.73
0.018
0.69
0.003


LGALS3
0.59
0.003
0.54
<.001


LIG3
0.75
0.044




MAP3K7
0.66
0.003
0.79
0.031


MCM3
0.73
0.013
0.80
0.034


MGMT
0.61
0.001
0.71
0.007


MGST1


0.75
0.017


MLXIP
0.70
0.013




MMP2
0.57
<.001
0.72
0.010


MMP7
0.69
0.009




MPPED2
0.70
0.009
0.59
<.001


MSH6
0.78
0.046




MTA1
0.69
0.007




MTSS1
0.55
<.001
0.54
<.001


MYBPC1
0.45
<.001
0.45
<.001


NCAM1
0.51
<.001
0.65
<.001


NCAPD3
0.42
<.001
0.53
<.001


NCOR2
0.68
0.002




NDUFS5
0.66
0.001
0.70
0.013


NEXN
0.48
<.001
0.62
<.001


NFAT5
0.55
<.001
0.67
0.001


NFKBIA


0.79
0.048


NRG1
0.58
0.001
0.62
0.001


OLFML3
0.42
<.001
0.58
<.001


OMD
0.67
0.004
0.71
0.004


OR51E2
0.65
<.001
0.76
0.007


PAGE4
0.27
<.001
0.46
<.001


PCA3
0.68
0.004




PCDHGB7
0.70
0.025
0.65
<.001


PGF
0.62
0.001




PGR
0.63
0.028




PHTF2
0.69
0.033




PLP2
0.54
<.001
0.71
0.003


PPAP2B
0.41
<.001
0.54
<.001


PPP1R12A
0.48
<.001
0.60
<.001


PRIMA1
0.62
0.003
0.65
<.001


PRKAR1B
0.70
0.009




PRKAR2B


0.79
0.038


PRKCA
0.37
<.001
0.55
<.001


PRKCB
0.47
<.001
0.56
<.001


PTCH1
0.70
0.021




PTEN
0.66
0.010
0.64
<.001


PTGER3


0.76
0.015


PTGS2
0.70
0.013
0.68
0.005


PTH1R
0.48
<.001




PTK2B
0.67
0.014
0.69
0.002


PYCARD
0.72
0.023




RAB27A


0.76
0.017


RAGE
0.77
0.040
0.57
<.001


RARB
0.66
0.002
0.69
0.002


RECK
0.65
<.001




RHOA
0.73
0.043




RHOB
0.61
0.005
0.62
<.001


RND3
0.63
0.006
0.66
<.001


SDHC


0.69
0.002


SEC23A
0.61
<.001
0.74
0.010


SEMA3A
0.49
<.001
0.55
<.001


SERPINA3
0.70
0.034
0.75
0.020


SH3RF2
0.33
<.001
0.42
<.001


SLC22A3
0.23
<.001
0.37
<.001


SMAD4
0.33
<.001
0.39
<.001


SMARCC2
0.62
0.003
0.74
0.008


SMO
0.53
<.001
0.73
0.009


SORBS1
0.40
<.001
0.55
<.001


SPARCL1
0.42
<.001
0.63
<.001


SRD5A2
0.28
<.001
0.37
<.001


STS
0.52
<.001
0.63
<.001


STAT5A
0.60
<.001
0.75
0.020


STAT5B
0.54
<.001
0.65
<.001


STS


0.78
0.035


SUMO1
0.75
0.017
0.71
0.002


SVIL
0.45
<.001
0.62
<.001


TARP
0.72
0.017




TGFB1I1
0.37
<.001
0.53
<.001


TGFB2
0.61
0.025
0.59
<.001


TGFB3
0.46
<.001
0.60
<.001


TIMP2
0.62
0.001




TIMP3
0.55
<.001
0.76
0.019


TMPRSS2
0.71
0.014




TNF
0.65
0.010




TNFRSF10A
0.71
0.014
0.74
0.010


TNFRSF10B
0.74
0.030
0.73
0.016


TNFSF10


0.69
0.004


TP53


0.73
0.011


TP63
0.62
<.001
0.68
0.003


TPM1
0.43
<.001
0.47
<.001


TPM2
0.30
<.001
0.47
<.001


TPP2
0.58
<.001
0.69
0.001


TRA2A
0.71
0.006




TRAF3IP2
0.50
<.001
0.63
<.001


TRO
0.40
<.001
0.59
<.001


TRPC6
0.73
0.030




TRPV6


0.80
0.047


VCL
0.44
<.001
0.55
<.001


VEGFB
0.73
0.029




VIM
0.72
0.013




VTI1B
0.78
0.046




WDR19
0.65
<.001




WFDC1
0.50
<.001
0.72
0.010


YY1
0.75
0.045




ZFHX3
0.52
<.001
0.54
<.001


ZFP36
0.65
0.004
0.69
0.012


ZNF827
0.59
<.001
0.69
0.004









To identify genes associated with recurrence (cRFI, bRFI) in the primary and the highest Gleason pattern, each of 727 genes were analyzed in univariate models using specimens A1 and B2 (see Table 2, above). Tables 4A and 4B provide genes that were associated, positively or negatively, with cRFI and/or bRFI in the primary and/or highest Gleason pattern. Increased expression of genes in Table 4A is negatively associated with good prognosis, while increased expression of genes in Table 4B is positively associated with good prognosis.









TABLE 4A







Genes significantly (p < 0.05) associated with cRFI or bRFI in the primary


Gleason pattern or highest Gleason pattern with hazard ratio (HR) > 1.0


(increased expression is negatively associated with good prognosis)












cRFI
cRFI
bRFI
bRFI


Official
Primary Pattern
Highest Pattern
Primary Pattern
Highest Pattern















Symbol
HR
p-value
HR
p-value
HR
p-value
HR
p-value


















AKR1C3
1.304
0.022
1.312
0.013






ANLN
1.379
0.002
1.579
<.001
1.465
<.001
1.623
<.001


AQP2
1.184
0.027
1.276
<.001






ASAP2


1.442
0.006






ASPN
2.272
<.001
2.106
<.001
1.861
<.001
1.895
<.001


ATP5E
1.414
0.013
1.538
<.001






BAG5


1.263
0.044






BAX


1.332
0.026
1.327
0.012
1.438
0.002


BGN
1.947
<.001
2.061
<.001
1.339
0.017




BIRC5
1.497
<.001
1.567
<.001
1.478
<.001
1.575
<.001


BMP6
1.705
<.001
2.016
<.001
1.418
0.004
1.541
<.001


BMPR1B
1.401
0.013


1.325
0.016




BRCA2






1.259
0.007


BUB1
1.411
<.001
1.435
<.001
1.352
<.001
1.242
0.002


CADPS




1.387
0.009
1.294
0.027


CCNB1




1.296
0.016
1.376
0.002


CCNE2
1.468
<.001
1.649
<.001
1.729
<.001
1.563
<.001


CD276
1.678
<.001
1.832
<.001
1.581
<.001
1.385
0.002


CDC20
1.547
<.001
1.671
<.001
1.446
<.001
1.540
<.001


CDC6
1.400
0.003
1.290
0.030
1.403
0.002
1.276
0.019


CDH7
1.403
0.003
1.413
0.002






CDKN2B
1.569
<.001
1.752
<.001
1.333
0.017
1.347
0.006


CDKN2C
1.612
<.001
1.780
<.001
1.323
0.005
1.335
0.004


CDKN3
1.384
<.001
1.255
0.024
1.285
0.003
1.216
0.028


CENPF
1.578
<.001
1.692
<.001
1.740
<.001
1.705
<.001


CKS2
1.390
0.007
1.418
0.005
1.291
0.018




CLTC


1.368
0.045






COL1A1
1.873
<.001
2.103
<.001
1.491
<.001
1.472
<.001


COL1A2


1.462
0.001






COL3A1
1.827
<.001
2.005
<.001
1.302
0.012
1.298
0.018


COL4A1
1.490
0.002
1.613
<.001






COL8A1
1.692
<.001
1.926
<.001
1.307
0.013
1.317
0.010


CRISP3
1.425
0.001
1.467
<.001
1.242
0.045




CTHRC1
1.505
0.002
2.025
<.001
1.425
0.003
1.369
0.005


CTNND2




1.412
0.003




CXCR4
1.312
0.023
1.355
0.008






DDIT4
1.543
<.001
1.763
<.001






DYNLL1
1.290
0.039




1.201
0.004


EIF3H




1.428
0.012




ENY2
1.361
0.014


1.392
0.008
1.371
0.001


EZH2


1.311
0.010






F2R
1.773
<.001
1.695
<.001
1.495
<.001
1.277
0.018


FADD


1.292
0.018






FAM171B


1.285
0.036






FAP
1.455
0.004
1.560
0.001
1.298
0.022
1.274
0.038


FASN
1.263
0.035








FCGR3A


1.654
<.001
1.253
0.033
1.350
0.007


FGF5
1.219
0.030








GNPTAB
1.388
0.007
1.503
0.003
1.355
0.005
1.434
0.002


GPR68


1.361
0.008






GREM1
1.470
0.003
1.716
<.001
1.421
0.003
1.316
0.017


HDAC1




1.290
0.025




HDAC9


1.395
0.012






HRAS
1.424
0.006
1.447
0.020






HSD17B4
1.342
0.019
1.282
0.026
1.569
<.001
1.390
0.002


HSPA8
1.290
0.034








IGFBP3
1.333
0.022
1.442
0.003
1.253
0.040
1.323
0.005


INHBA
2.368
<.001
2.765
<.001
1.466
0.002
1.671
<.001


JAG1
1.359
0.006
1.367
0.005
1.259
0.024




KCNN2
1.361
0.011
1.413
0.005
1.312
0.017
1.281
0.030


KHDRBS3
1.387
0.006
1.601
<.001
1.573
<.001
1.353
0.006


KIAA0196






1.249
0.037


KIF4A
1.212
0.016


1.149
0.040
1.278
0.003


KLK14
1.167
0.023




1.180
0.007


KPNA2


1.425
0.009
1.353
0.005
1.305
0.019


KRT75






1.164
0.028


LAMA3




1.327
0.011




LAMB1


1.347
0.019






LAMC1
1.555
0.001
1.310
0.030


1.349
0.014


LIMS1






1.275
0.022


LOX




1.358
0.003
1.410
<.001


LTBP2
1.396
0.009
1.656
<.001
1.278
0.022




LUM


1.315
0.021






MANF




1.660
<.001
1.323
0.011


MCM2




1.345
0.011
1.387
0.014


MCM6
1.307
0.023
1.352
0.008


1.244
0.039


MELK
1.293
0.014
1.401
<.001
1.501
<.001
1.256
0.012


MMP11
1.680
<.001
1.474
<.001
1.489
<.001
1.257
0.030


MRPL13






1.260
0.025


MSH2


1.295
0.027






MYBL2
1.664
<.001
1.670
<.001
1.399
<.001
1.431
<.001


MYO6


1.301
0.033






NETO2
1.412
0.004
1.302
0.027
1.298
0.009




NFKB1




1.236
0.050




NOX4
1.492
<.001
1.507
0.001
1.555
<.001
1.262
0.019


NPM1




1.287
0.036




NRIP3


1.219
0.031


1.218
0.018


NRP1


1.482
0.002


1.245
0.041


OLFML2B


1.362
0.015






OR51E1




1.531
<.001
1.488
0.003


PAK6


1.269
0.033






PATE1
1.308
<.001
1.332
<.001
1.164
0.044




PCNA






1.278
0.020


PEX10
1.436
0.005
1.393
0.009






PGD
1.298
0.048


1.579
<.001




PGK1


1.274
0.023


1.262
0.009


PLA2G7




1.315
0.011
1.346
0.005


PLAU




1.319
0.010




PLK1
1.309
0.021
1.563
<.001
1.410
0.002
1.372
0.003


PLOD2


1.284
0.019
1.272
0.014
1.332
0.005


POSTN
1.599
<.001
1.514
0.002
1.391
0.005




PPP3CA




1.402
0.007
1.316
0.018


PSMD13
1.278
0.040
1.297
0.033
1.279
0.017
1.373
0.004


PTK6
1.640
<.001
1.932
<.001
1.369
0.001
1.406
<.001


PTTG1
1.409
<.001
1.510
<.001
1.347
0.001
1.558
<.001


RAD21
1.315
0.035
1.402
0.004
1.589
<.001
1.439
<.001


RAF1




1.503
0.002




RALA
1.521
0.004
1.403
0.007
1.563
<.001
1.229
0.040


RALBP1




1.277
0.033




RGS7
1.154
0.015
1.266
0.010






RRM1
1.570
0.001
1.602
<.001






RRM2
1.368
<.001
1.289
0.004
1.396
<.001
1.230
0.015


SAT1
1.482
0.016
1.403
0.030






SDC1




1.340
0.018
1.396
0.018


SEC14L1


1.260
0.048


1.360
0.002


SESN3
1.485
<.001
1.631
<.001
1.232
0.047
1.292
0.014


SFRP4
1.800
<.001
1.814
<.001
1.496
<.001
1.289
0.027


SHMT2
1.807
<.001
1.658
<.001
1.673
<.001
1.548
<.001


SKIL




1.327
0.008




SLC25A21




1.398
0.001
1.285
0.018


SOX4




1.286
0.020
1.280
0.030


SPARC
1.539
<.001
1.842
<.001


1.269
0.026


SPP1


1.322
0.022






SQLE


1.359
0.020
1.270
0.036




STMN1
1.402
0.007
1.446
0.005
1.279
0.031




SULF1


1.587
<.001






TAF2






1.273
0.027


TFDP1


1.328
0.021
1.400
0.005
1.416
0.001


THBS2
1.812
<.001
1.960
<.001
1.320
0.012
1.256
0.038


THY1
1.362
0.020
1.662
<.001






TK1


1.251
0.011
1.377
<.001
1.401
<.001


TOP2A
1.670
<.001
1.920
<.001
1.869
<.001
1.927
<.001


TPD52
1.324
0.011
1.366
0.002
1.351
0.005




TPX2
1.884
<.001
2.154
<.001
1.874
<.001
1.794
<.001


UAP1




1.244
0.044




UBE2C
1.403
<.001
1.541
<.001
1.306
0.002
1.323
<.001


UBE2T
1.667
<.001
1.282
0.023
1.502
<.001
1.298
0.005


UGT2B15
1.295
0.001
1.275
0.002






UGT2B17






1.294
0.025


UHRF1
1.454
<.001
1.531
<.001
1.257
0.029




VCPIP1
1.390
0.009
1.414
0.004
1.294
0.021
1.283
0.021


WNT5A


1.274
0.038
1.298
0.020




XIAP




1.464
0.006




ZMYND8


1.277
0.048






ZWINT
1.259
0.047
















TABLE 4B







Genes significantly (p < 0.05) associated with cRFI or bRFI in the primary


Gleason pattern or highest Gleason pattern with hazard ratio (HR) < 1.0


(increased expression is positively associated with good prognosis)












cRFI
cRFI
bRFI
bRFI


Official
Primary Pattern
Highest Pattern
Primary Pattern
Highest Pattern















Symbol
HR
p-value
HR
p-value
HR
p-value
HR
p-value


















AAMP
0.564
<.001
0.571
.001
0.764
0.037
0.786
0.034


ABCA5
0.755
<.001
0.695
<.001


0.800
0.006


ABCB1
0.777
0.026








ABCG2
0.788
0.033
0.784
0.040
0.803
0.018
0.750
0.004


ABHD2


0.734
0.011






ACE


0.782
0.048






ACOX2
0.639
<.001
0.631
<.001
0.713
<.001
0.716
0.002


ADH5
0.625
<.001
0.637
<.001
0.753
0.026




AKAP1
0.764
0.006
0.800
0.005
0.837
0.046




AKR1C1
0.773
0.033


0.802
0.032




AKT1


0.714
0.005






AKT3
0.811
0.015
0.809
0.021






ALDH1A2
0.606
<.001
0.498
<.001
0.613
<.001
0.624
<.001


AMPD3




0.793
0.024




ANPEP
0.584
<.001
0.493
<.001






ANXA2
0.753
0.013
0.781
0.036
0.762
0.008
0.795
0.032


APRT


0.758
0.026
0.780
0.044
0.746
0.008


ATXN1
0.673
0.001
0.776
0.029
0.809
0.031
0.812
0.043


AXIN2
0.674
<.001
0.571
<.001
0.776
0.005
0.757
0.005


AZGP1
0.585
<.001
0.652
<.001
0.664
<.001
0.746
<.001


BAD


0.765
0.023






BCL2
0.788
0.033
0.778
0.036






BDKRB1
0.728
0.039








BIK


0.712
0.005






BIN1
0.607
<.001
0.724
0.002
0.726
<.001
0.834
0.034


BTG3




0.847
0.034




BTRC
0.688
0.001
0.713
0.003






C7
0.589
<.001
0.639
<.001
0.629
<.001
0.691
<.001


CADM1
0.546
<.001
0.529
<.001
0.743
0.008
0.769
0.015


CASP1
0.769
0.014
0.799
0.028
0.799
0.010
0.815
0.018


CAV1
0.736
0.011
0.711
0.005
0.675
<.001
0.743
0.006


CAV2


0.636
0.010
0.648
0.012
0.685
0.012


CCL2
0.759
0.029
0.764
0.024






CCNH
0.689
<.001
0.700
<.001






CD164
0.664
<.001
0.651
<.001






CD1A




0.687
0.004




CD44
0.545
<.001
0.600
<.001
0.788
0.018
0.799
0.023


CD82
0.771
0.009
0.748
0.004






CDC25B
0.755
0.006


0.817
0.025




CDK14
0.845
0.043








CDK2






0.819
0.032


CDK3


0.733
0.005
0.772
0.006
0.838
0.017


CDKN1A


0.766
0.041






CDKN1C
0.662
<.001
0.712
0.002
0.693
<.001
0.761
0.009


CHN1
0.788
0.036








COL6A1
0.608
<.001
0.767
0.013
0.706
<.001
0.775
0.007


CSF1
0.626
<.001
0.709
0.003






CSK




0.837
0.029




C SRP1
0.793
0.024
0.782
0.019






C TNNB 1
0.898
0.042


0.885
<.001




CTSB
0.701
0.004
0.713
0.007
0.715
0.002
0.803
0.038


CTSK




0.815
0.042




CXCL12
0.652
<.001
0.802
0.044
0.711
0.001




CYP3A5
0.463
<.001
0.436
<.001
0.727
0.003




CYR61
0.652
0.002
0.676
0.002






DAP
0.761
0.026
0.775
0.025
0.802
0.048




DARC
0.725
0.005
0.792
0.032






DDR2
0.719
0.001
0.763
0.008






DES
0.619
<.001
0.737
0.005
0.638
<.001
0.793
0.017


DHRS9
0.642
0.003








DHX9
0.888
<.001








DLC1
0.710
0.007
0.715
0.009






DLGAP1
0.613
<.001
0.551
<.001


0.779
0.049


DNIVI3
0.679
<.001
0.812
0.037






DPP4
0.591
<.001
0.613
<.001
0.761
0.003




DPT
0.613
<.001
0.576
<.001
0.647
<.001
0.677
<.001


DUSP1
0.662
0.001
0.665
0.001


0.785
0.024


DUSP6
0.713
0.005
0.668
0.002






EDNRA
0.702
0.002
0.779
0.036






EGF
0.738
0.028








EGR1
0.569
<.001
0.577
<.001


0.782
0.022


EGR3
0.601
<.001
0.619
<.001


0.800
0.038


EIF253






0.756
0.015


EIF5
0.776
0.023
0.787
0.028






ELK4
0.628
<.001
0.658
<.001






EPHA2
0.720
0.011
0.663
0.004






EPHA3
0.727
0.003


0.772
0.005




ERBB2
0.786
0.019
0.738
0.003
0.815
0.041




ERBB3
0.728
0.002
0.711
0.002
0.828
0.043
0.813
0.023


ERCC1
0.771
0.023
0.725
0.007
0.806
0.049
0.704
0.002


EREG




0.754
0.016
0.777
0.034


ESR2


0.731
0.026






FAAH
0.708
0.004
0.758
0.012
0.784
0.031
0.774
0.007


FAM107A
0.517
<.001
0.576
<.001
0.642
<.001
0.656
<.001


FAM13C
0.568
<.001
0.526
<.001
0.739
0.002
0.639
<.001


FAS
0.755
0.014








FASLG


0.706
0.021






FGF10
0.653
<.001
0.685
<.001
0.766
0.022




FGF17
0.746
0.023
0.781
0.015
0.805
0.028




FGF7
0.794
0.030
0.820
0.037
0.811
0.040




FGFR2
0.683
<.001
0.686
<.001
0.674
<.001
0.703
<.001


FKBP5


0.676
0.001






FLNA
0.653
<.001
0.741
0.010
0.682
<.001
0.771
0.016


FLNC
0.751
0.029
0.779
0.047
0.663
<.001
0.725
<.001


FLT1


0.799
0.044






FOS
0.566
<.001
0.543
<.001


0.757
0.006


FOXO1




0.816
0.039
0.798
0.023


FOXQ1
0.753
0.017
0.757
0.024
0.804
0.018




FYN
0.779
0.031








GADD45B
0.590
<.001
0.619
<.001






GDF15
0.759
0.019
0.794
0.048






GHR
0.702
0.005
0.630
<.001
0.673
<.001
0.590
<.001


GNRH1




0.742
0.014




GPM6B
0.653
<.001
0.633
<.001
0.696
<.001
0.768
0.007


GSN
0.570
<.001
0.697
0.001
0.697
<.001
0.758
0.005


GSTM1
0.612
<.001
0.588
<.001
0.718
<.001
0.801
0.020


GSTM2
0.540
<.001
0.630
<.001
0.602
<.001
0.706
<.001


HGD
0.796
0.020
0.736
0.002






HIRIP3
0.753
0.011


0.824
0.050




HK1
0.684
<.001
0.683
<.001
0.799
0.011
0.804
0.014


HLA-G


0.726
0.022






HLF
0.555
<.001
0.582
<.001
0.703
<.001
0.702
<.001


HNF1B
0.690
<.001
0.585
<.001






HPS1
0.744
0.003
0.784
0.020
0.836
0.047




HSD3B2






0.733
0.016


HSP90AB1
0.801
0.036








HSPA5


0.776
0.034






HSPB1
0.813
0.020








HSPB2
0.762
0.037


0.699
0.002
0.783
0.034


HSPG2




0.794
0.044




ICAM1
0.743
0.024
0.768
0.040






IER3
0.686
0.002
0.663
<.001






IFIT1
0.649
<.001
0.761
0.026






IGF1
0.634
<.001
0.537
<.001
0.696
<.001
0.688
<.001


IGF2




0.732
0.004




IGFBP2
0.548
<.001
0.620
<.001






IGFBP5
0.681
<.001








IGFBP6
0.577
<.001


0.675
<.001




IL1B
0.712
0.005
0.742
0.009






IL6
0.763
0.028








IL6R


0.791
0.039






IL6ST
0.585
<.001
0.639
<.001
0.730
0.002
0.768
0.006


IL8
0.624
<.001
0.662
0.001






ILK
0.712
0.009
0.728
0.012
0.790
0.047
0.790
0.042


ING5
0.625
<.001
0.658
<.001
0.728
0.002




ITGA5
0.728
0.006
0.803
0.039






ITGA6
0.779
0.007
0.775
0.006






ITGA7
0.584
<.001
0.700
0.001
0.656
<.001
0.786
0.014


ITGAD


0.657
0.020






ITGB4
0.718
0.007
0.689
<.001
0.818
0.041




ITGB5


0.801
0.050






ITPR1
0.707
0.001








JUN
0.556
<.001
0.574
<.001


0.754
0.008


JUNB
0.730
0.017
0.715
0.010






KIT
0.644
0.004
0.705
0.019
0.605
<.001
0.659
0.001


KLC1
0.692
0.003
0.774
0.024
0.747
0.008




KLF6
0.770
0.032
0.776
0.039






KLK1
0.646
<.001
0.652
0.001
0.784
0.037




KLK10


0.716
0.006






KLK2
0.647
<.001
0.628
<.001


0.786
0.009


KLK3
0.706
<.001
0.748
<.001


0.845
0.018


KRT1






0.734
0.024


KRT15
0.627
<.001
0.526
<.001
0.704
<.001
0.782
0.029


KRT18
0.624
<.001
0.617
<.001
0.738
0.005
0.760
0.005


KRT5
0.640
<.001
0.550
<.001
0.740
<.001
0.798
0.023


KRT8
0.716
0.006
0.744
0.008






L1CAM
0.738
0.021
0.692
0.009


0.761
0.036


LAG3
0.741
0.013
0.729
0.011






LAMA4
0.686
0.011


0.592
0.003




LAMA5






0.786
0.025


LAMB3
0.661
<.001
0.617
<.001
0.734
<.001




LGALS3
0.618
<.001
0.702
0.001
0.734
0.001
0.793
0.012


LIG3
0.705
0.008
0.615
<.001






LRP1
0.786
0.050


0.795
0.023
0.770
0.009


MAP3K7




0.789
0.003




MGMT
0.632
<.001
0.693
<.001






MICA
0.781
0.014
0.653
<.001


0.833
0.043


MPPED2
0.655
<.001
0.597
<.001
0.719
<.001
0.759
0.006


MSH6
0.793
0.015








MTSS1
0.613
<.001


0.746
0.008




MVP
0.792
0.028
0.795
0.045
0.819
0.023




MYBPC1
0.648
<.001
0.496
<.001
0.701
<.001
0.629
<.001


NCAM1




0.773
0.015




NCAPD3
0.574
<.001
0.463
<.001
0.679
<.001
0.640
<.001


NEXN
0.701
0.002
0.791
0.035
0.725
0.002
0.781
0.016


NFAT5
0.515
<.001
0.586
<.001
0.785
0.017




NFATC2
0.753
0.023








NFKB IA
0.778
0.037








NRG1
0.644
0.004
0.696
0.017
0.698
0.012




OAZ1
0.777
0.034
0.775
0.022






OLFML3
0.621
<.001
0.720
0.001
0.600
<.001
0.626
<.001


OMD
0.706
0.003








OR51E2
0.820
0.037
0.798
0.027






PAGE4
0.549
<.001
0.613
<.001
0.542
<.001
0.628
<.001


PCA3
0.684
<.001
0.635
<.001






PCDHGB7
0.790
0.045


0.725
0.002
0.664
<.001


PGF
0.753
0.017








PGR
0.740
0.021
0.728
0.018






PIK3CG
0.803
0.024








PLAUR
0.778
0.035








PLG






0.728
0.028


PPAP2B
0.575
<.001
0.629
<.001
0.643
<.001
0.699
<.001


PPP1R12A
0.647
<.001
0.683
0.002
0.782
0.023
0.784
0.030


PRIMA1
0.626
<.001
0.658
<.001
0.703
0.002
0.724
0.003


PRKCA
0.642
<.001
0.799
0.029
0.677
0.001
0.776
0.006


PRKCB
0.675
0.001


0.648
<.001
0.747
0.006


PROM1
0.603
0.018


0.659
0.014
0.493
0.008


PTCH1
0.680
0.001


0.753
0.010
0.789
0.018


PTEN
0.732
0.002
0.747
0.005
0.744
<.001
0.765
0.002


PTGS2
0.596
<.001
0.610
<.001






PTH1R
0.767
0.042


0.775
0.028
0.788
0.047


PTHLH
0.617
0.002
0.726
0.025
0.668
0.002
0.718
0.007


PTK2B
0.744
0.003
0.679
<.001
0.766
0.002
0.726
<.001


PTPN1
0.760
0.020
0.780
0.042






PYCARD


0.748
0.012






RAB27A


0.708
0.004






RAB30
0.755
0.008








RAGE


0.817
0.048






RAP1B




0.818
0.050




RARB
0.757
0.007
0.677
<.001
0.789
0.007
0.746
0.003


RASSF1






0.816
0.035


RHOB
0.725
0.009
0.676
0.001


0.793
0.039


RLN1
0.742
0.033
0.762
0.040






RND3
0.636
<.001
0.647
<.001






RNF114


0.749
0.011






SDC2




0.721
0.004




SDHC
0.725
0.003
0.727
0.006






SEMA3A
0.757
0.024
0.721
0.010






SERPINA3
0.716
0.008
0.660
0.001






SERPINB5
0.747
0.031
0.616
0.002






SH3RF2
0.577
<.001
0.458
<.001
0.702
<.001
0.640
<.001


SLC22A3
0.565
<.001
0.540
<.001
0.747
0.004
0.756
0.007


SMAD4
0.546
<.001
0.573
<.001
0.636
<.001
0.627
<.001


SMARCD1
0.718
<.001
0.775
0.017






SMO
0.793
0.029
0.754
0.021


0.718
0.003


SOD1
0.757
0.049
0.707
0.006






SORBS1
0.645
<.001
0.716
0.003
0.693
<.001
0.784
0.025


SPARCL1
0.821
0.028


0.829
0.014
0.781
0.030


SPDEF
0.778
<.001








SPINT1
0.732
0.009
0.842
0.026






SRC
0.647
<.001
0.632
<.001






SRD5A1




0.813
0.040




SRD5A2
0.489
<.001
0.533
<.001
0.544
<.001
0.611
<.001


STS
0.713
0.002
0.783
0.011
0.725
<.001
0.827
0.025


STAT3
0.773
0.037
0.759
0.035






STAT5A
0.695
<.001
0.719
0.002
0.806
0.020
0.783
0.008


STAT5B
0.633
<.001
0.655
<.001


0.814
0.028


SUMO1
0.790
0.015








SVIL
0.659
<.001
0.713
0.002
0.711
0.002
0.779
0.010


TARP






0.800
0.040


TBP
0.761
0.010








TFF3
0.734
0.010
0.659
<.001






TGFB1I1
0.618
<.001
0.693
0.002
0.637
<.001
0.719
0.004


TGFB2
0.679
<.001
0.747
0.005
0.805
0.030




TGFB3




0.791
0.037




TGFBR2




0.778
0.035




TIMP3




0.751
0.011




TMPRSS2
0.745
0.003
0.708
<.001






TNF


0.670
0.013


0.697
0.015


TNFRSF10A
0.780
0.018
0.752
0.006
0.817
0.032




TNFRSF10B
0.576
<.001
0.655
<.001
0.766
0.004
0.778
0.002


TNFRSF18
0.648
0.016


0.759
0.034




TNFSF10
0.653
<.001
0.667
0.004






TP53


0.729
0.003






TP63
0.759
0.016
0.636
<.001
0.698
<.001
0.712
0.001


TPM1
0.778
0.048
0.743
0.012
0.783
0.032
0.811
0.046


TPM2
0.578
<.001
0.634
<.001
0.611
<.001
0.710
0.001


TPP2


0.775
0.037






TRAF3IP2
0.722
0.002
0.690
<.001
0.792
0.021
0.823
0.049


TRO
0.744
0.003
0.725
0.003
0.765
0.002
0.821
0.041


TUBB2A
0.639
<.001
0.625
<.001






TYMP
0.786
0.039








VCL
0.594
<.001
0.657
0.001
0.682
<.001




VEGFA



0.762
0.024





VEGFB
0.795
0.037








VIM
0.739
0.009


0.791
0.021




WDR19






0.776
0.015


WFDC1




0.746
<.001




YY1
0.683
0.001


0.728
0.002




ZFHX3
0.684
<.001
0.661
<.001
0.801
0.010
0.762
0.001


ZFP36
0.605
<.001
0.579
<.001


0.815
0.043


ZNF827
0.624
<.001
0.730
0.007
0.738
0.004









Tables 5A and 5B provide genes that were significantly associated (p<0.05), positively or negatively, with recurrence (cRFI, bRFI) after adjusting for AUA risk group in the primary and/or highest Gleason pattern. Increased expression of genes in Table 5A is negatively associated with good prognosis, while increased expression of genes in Table 5B is positively associated with good prognosis.









TABLE 5A







Genes significantly (p < 0.05) associated with cRFI or bRFI after adjustment for AIA


risk grous in primary Gleason pattern or highest Gleason pattern with hazard


ratio (HR) > 1.0 (increased expression is positively associated with good prognosis)












cRFI
cRFI
bRFI
bRFI


Official
Primary Pattern
Highest Pattern
Primary Pattern
Highest Pattern















Symbol
HR
p-value
HR
p-value
HR
p-value
HR
p-value


















AKR1C3
1.315
0.018
1.283
0.024






ALOX12






1.198
0.024


ANLN
1.406
<.001
1.519
<.001
1.485
<.001
1.632
<.001


AQP2
1.209
<.001
1.302
<.001






ASAP2


1.582
<.001
1.333
0.011
1.307
0.019


ASPN
1.872
<.001
1.741
<.001
1.638
<.001
1.691
<.001


ATP5E
1.309
0.042
1.369
0.012






BAG5


1.291
0.044






BAX




1.298
0.025
1.420
0.004


BGN
1.746
<.001
1.755
<.001






BIRC5
1.480
<.001
1.470
<.001
1.419
<.001
1.503
<.001


BMP6
1.536
<.001
1.815
<.001
1.294
0.033
1.429
0.001


BRCA2






1.184
0.037


BUB1
1.288
0.001
1.391
<.001
1.254
<.001
1.189
0.018


CACNA1D


1.313
0.029






CADPS




1.358
0.007
1.267
0.022


CASP3




1.251
0.037




CCNB1




1.261
0.033
1.318
0.005


CCNE2
1.345
0.005
1.438
<.001
1.606
<.001
1.426
<.001


CD276
1.482
0.002
1.668
<.001
1.451
<.001
1.302
0.011


CDC20
1.417
<.001
1.547
<.001
1.355
<.001
1.446
<.001


CDC6
1.340
0.011
1.265
0.046
1.367
0.002
1.272
0.025


CDH7
1.402
0.003
1.409
0.002






CDKN2B
1.553
<.001
1.746
<.001
1.340
0.014
1.369
0.006


CDKN2C
1.411
<.001
1.604
<.001
1.220
0.033




CDKN3
1.296
0.004
1.226
0.015






CENPF
1.434
0.002
1.570
<.001
1.633
<.001
1.610
<.001


CKS2
1.419
0.008
1.374
0.022
1.380
0.004




COL1A1
1.677
<.001
1.809
<.001
1.401
<.001
1.352
0.003


COL1A2


1.373
0.010






COL3A1
1.669
<.001
1.781
<.001
1.249
0.024
1.234
0.047


COL4A1
1.475
0.002
1.513
0.002






COL8A1
1.506
0.001
1.691
<.001






CRISP3
1.406
0.004
1.471
<.001






CTHRC1
1.426
0.009
1.793
<.001
1.311
0.019




CTNND2




1.462
<.001




DDIT4
1.478
0.003
1.783
<.001


1.236
0.039


DYNLL1
1.431
0.002
1.193
0.004






EIF3H




1.372
0.027




ENY2




1.325
0.023
1.270
0.017


ERG
1.303
0.041








EZH2


1.254
0.049






F2R
1.540
0.002
1.448
0.006
1.286
0.023




FADD
1.235
0.041
1.404
<.001






FAP
1.386
0.015
1.440
0.008
1.253
0.048




FASN
1.303
0.028








FCGR3A
1.439
0.011




1.262
0.045


FGF5
1.289
0.006








GNPTAB
1.290
0.033
1.369
0.022
1.285
0.018
1.355
0.008


GPR68


1.396
0.005






GREM1
1.341
0.022
1.502
0.003
1.366
0.006




HDAC1




1.329
0.016




HDAC9


1.378
0.012






HRAS
1.465
0.006








HSD17B4




1.442
<.001
1.245
0.028


IGFBP3


1.366
0.019


1.302
0.011


INHBA
2.000
<.001
2.336
<.001


1.486
0.002


JAG1
1.251
0.039








KCNN2
1.347
0.020
1.524
<.001
1.312
0.023
1.346
0.011


KHDRBS3


1.500
0.001
1.426
0.001
1.267
0.032


KIAA0196






1.272
0.028


KIF4A
1.199
0.022




1.262
0.004


KPNA2




1.252
0.016




LAMA3




1.332
0.004
1.356
0.010


LAMB1


1.317
0.028






LAMC1
1.516
0.003
1.302
0.040


1.397
0.007


LIMS1






1.261
0.027


LOX




1.265
0.016
1.372
0.001


LTBP2


1.477
0.002






LUM


1.321
0.020






MANF




1.647
<.001
1.284
0.027


MCM2




1.372
0.003
1.302
0.032


MCM3


1.269
0.047






MCM6


1.276
0.033


1.245
0.037


MELK


1.294
0.005
1.394
<.001




MK167
1.253
0.028
1.246
0.029






MMP11
1.557
<.001
1.290
0.035
1.357
0.005




MRPL13






1.275
0.003


MSH2


1.355
0.009






MYBL2
1.497
<.001
1.509
<.001
1.304
0.003
1.292
0.007


MY06


1.367
0.010






NDRG1
1.270
0.042




1.314
0.025


NEK2


1.338
0.020


1.269
0.026


NETO2
1.434
0.004
1.303
0.033
1.283
0.012




NOX4
1.413
0.006
1.308
0.037
1.444
<.001




NRIP3






1.171
0.026


NRP1


1.372
0.020






ODC1




1.450
<.001




OR51E1




1.559
<.001
1.413
0.008


PAK6






1.233
0.047


PATE1
1.262
<.001
1.375
<.001
1.143
0.034
1.191
0.036


PCNA




1.227
0.033
1.318
0.003


PEX10
1.517
<.001
1.500
0.001






PGD
1.363
0.028
1.316
0.039
1.652
<.001




PGK1


1.224
0.034


1.206
0.024


PIM1




1.205
0.042




PLA2G7




1.298
0.018
1.358
0.005


PLAU




1.242
0.032




PLK1


1.464
0.001
1.299
0.018
1.275
0.031


PLOD2




1.206
0.039
1.261
0.025


POSTN
1.558
0.001
1.356
0.022
1.363
0.009




PPP3CA




1.445
0.002




PSMD13




1.301
0.017
1.411
0.003


PTK2


1.318
0.031






PTK6
1.582
<.001
1.894
<.001
1.290
0.011
1.354
0.003


PTTG1
1.319
0.004
1.430
<.001
1.271
0.006
1.492
<.001


RAD21


1.278
0.028
1.435
0.004
1.326
0.008


RAF1




1.504
<.001




RALA
1.374
0.028


1.459
0.001




RGS7


1.203
0.031






RRM1
1.535
0.001
1.525
<.001






RRM2
1.302
0.003
1.197
0.047
1.342
<.001




SAT1
1.374
0.043








SDC1




1.344
0.011
1.473
0.008


SEC14L1






1.297
0.006


SESN3
1.337
0.002
1.495
<.001


1.223
0.038


SFRP4
1.610
<.001
1.542
0.002
1.370
0.009




SHMT2
1.567
0.001
1.522
<.001
1.485
0.001
1.370
<.001


SKIL




1.303
0.008




SLC25A21




1.287
0.020
1.306
0.017


SLC44A1


1.308
0.045






SNRPB2
1.304
0.018








SOX4




1.252
0.031




SPARC
1.445
0.004
1.706
<.001


1.269
0.026


SPP1


1.376
0.016






SQLE


1.417
0.007
1.262
0.035




STAT1






1.209
0.029


STMN1
1.315
0.029








SULF1


1.504
0.001






TAF2




1.252
0.048
1.301
0.019


TFDP1




1.395
0.010
1.424
0.002


THBS2
1.716
<.001
1.719
<.001






THY1
1.343
0.035
1.575
0.001






TK1




1.320
<.001
1.304
<.001


TOP2A
1.464
0.001
1.688
<.001
1.715
<.001
1.761
<.001


TPD52




1.286
0.006
1.258
0.023


TPX2
1.644
<.001
1.964
<.001
1.699
<.001
1.754
<.001


TYMS






1.315
0.014


UBE2C
1.270
0.019
1.558
<.001
1.205
0.027
1.333
<.001


UBE2G1
1.302
0.041








UBE2T
1.451
<.001


1.309
0.003




UGT2B15


1.222
0.025






UHRF1
1.370
0.003
1.520
<.001
1.247
0.020




VCPIP1


1.332
0.015






VTI1B




1.237
0.036




XIAP




1.486
0.008




ZMYND8


1.408
0.007






ZNF3






1.284
0.018


ZWINT
1.289
0.028
















TABLE 5B







Genes significantly (p < 0.05) associated with cRFI or bRFI after adjustment for AUA


risk group in the primary Gleason pattern or highest Gleason pattern with hazard


ratio (HR) < 1.0 (increased expression is positively associated with good prognosis)











Table 5B
cRFI
cRFI
bRFI
bRFI


Official
Primary Pattern
Highest Pattern
Primary Pattern
Highest Pattern















Symbol
HR
p-value
HR
p-value
HR
p-value
HR
p-value


















AAMP
0.535
<.001
0.581
<.001
0.700
0.002
0.759
0.006


ABCA5
0.798
0.007
0.745
0.002


0.841
0.037


ABCC1


0.800
0.044






ABCC4


0.787
0.022






ABHD2


0.768
0.023






ACOX2
0.678
0.002
0.749
0.027
0.759
0.004




ADH5
0.645
<.001
0.672
0.001






AGTR1
0.780
0.030








AKAP1
0.815
0.045
0.758
<.001






AKT1


0.732
0.010






ALDH1A2
0.646
<.001
0.548
<.001
0.671
<.001
0.713
0.001


ANPEP
0.641
<.001
0.535
<.001






ANXA2
0.772
0.035


0.804
0.046




ATXN1
0.654
<.001
0.754
0.020
0.797
0.017




AURKA


0.788
0.030






AXIN2
0.744
0.005
0.655
<.001






AZGP1
0.656
<.001
0.676
<.001
0.754
0.001
0.791
0.004


BAD


0.700
0.004






BIN1
0.650
<.001
0.764
0.013
0.803
0.015




BTG3




0.836
0.025




BTRC
0.730
0.005








C7
0.617
<.001
0.680
<.001
0.667
<.001
0.755
0.005


CADM1
0.559
<.001
0.566
<.001
0.772
0.020
0.802
0.046


CASP1
0.781
0.030
0.779
0.021
0.818
0.027
0.828
0.036


CAV1




0.775
0.034




CAV2


0.677
0.019






CCL2


0.752
0.023






CCNH
0.679
<.001
0.682
<.001






CD164
0.721
0.002
0.724
0.005






CD1A




0.710
0.014




CD44
0.591
<.001
0.642
<.001






CD82
0.779
0.021
0.771
0.024






CDC25B
0.778
0.035


0.818
0.023




CDK14
0.788
0.011








CDK3
0.752
0.012


0.779
0.005
0.841
0.020


CDKN1A
0.770
0.049
0.712
0.014






CDKN1C
0.684
<.001


0.697
<.001




CHN1
0.772
0.031








COL6A1
0.648
<.001
0.807
0.046
0.768
0.004




CSF1
0.621
<.001
0.671
0.001






CTNNB1




0.905
0.008




CTSB
0.754
0.030
0.716
0.011
0.756
0.014




CXCL12
0.641
<.001
0.796
0.038
0.708
<.001




CYP3A5
0.503
<.001
0.528
<.001
0.791
0.028




CYR61
0.639
0.001
0.659
0.001


0.797
0.048


DARC




0.707
0.004




DDR2




0.750
0.011




DES
0.657
<.001
0.758
0.022
0.699
<.001




DHRS9
0.625
0.002








DHX9
0.846
<.001








DIAPH1
0.682
0.007
0.723
0.008
0.780
0.026




DLC1
0.703
0.005
0.702
0.008






DLGAP1
0.703
0.008
0.636
<.001






DNM3
0.701
0.001


0.817
0.042




DPP4
0.686
<.001
0.716
0.001






DPT
0.636
<.001
0.633
<.001
0.709
0.006
0.773
0.024


DUSP1
0.683
0.006
0.679
0.003






DUSP6
0.694
0.003
0.605
<.001






EDN1




0.773
0.031




EDNRA
0.716
0.007








EGR1
0.575
<.001
0.575
<.001


0.771
0.014


EGR3
0.633
0.002
0.643
<.001


0.792
0.025


EIF4E
0.722
0.002








ELK4
0.710
0.009
0.759
0.027






ENPP2
0.786
0.039








EPHA2


0.593
0.001






EPHA3
0.739
0.006


0.802
0.020




ERBB2


0.753
0.007






ERBB3
0.753
0.009
0.753
0.015






ERCC1






0.727
0.001


EREG




0.722
0.012
0.769
0.040


ESR1


0.742
0.015






FABP5
0.756
0.032








FAM107A
0.524
<.001
0.579
<.001
0.688
<.001
0.699
0.001


FAM13C
0.639
<.001
0.601
<.001
0.810
0.019
0.709
<.001


FAS
0.770
0.033








FASLG
0.716
0.028
0.683
0.017






FGF10




0.798
0.045




FGF17


0.718
0.018
0.793
0.024
0.790
0.024


FGFR2
0.739
0.007
0.783
0.038
0.740
0.004




FGFR4


0.746
0.050






FKBP5


0.689
0.003






FLNA
0.701
0.006
0.766
0.029
0.768
0.037




FLNC




0.755
<.001
0.820
0.022


FLT1


0.729
0.008






FOS
0.572
<.001
0.536
<.001


0.750
0.005


FOXQ1
0.778
0.033


0.820
0.018




FYN
0.708
0.006








GADD45B
0.577
<.001
0.589
<.001






GDF15
0.757
0.013
0.743
0.006






GHR


0.712
0.004


0.679
0.001


GNRH1




0.791
0.048




GPM6B
0.675
<.001
0.660
<.001
0.735
<.001
0.823
0.049


GSK3B
0.783
0.042








GSN
0.587
<.001
0.705
0.002
0.745
0.004
0.796
0.021


GSTM1
0.686
0.001
0.631
<.001
0.807
0.018




GSTM2
0.607
<.001
0.683
<.001
0.679
<.001
0.800
0.027


HIRIP3
0.692
<.001


0.782
0.007




HK1
0.724
0.002
0.718
0.002






HLF
0.580
<.001
0.571
<.001
0.759
0.008
0.750
0.004


HNF1B


0.669
<.001






HPS1
0.764
0.008








HSD17B10
0.802
0.045








HSD17B2




0.723
0.048




HSD3B2






0.709
0.010


HSP90AB1
0.780
0.034


0.809
0.041




HSPA5


0.738
0.017






HSPB1
0.770
0.006
0.801
0.032






HSPB2




0.788
0.035




ICAM1
0.728
0.015
0.716
0.010






IER3
0.735
0.016
0.637
<.001


0.802
0.035


IFIT1
0.647
<.001
0.755
0.029






IGF1
0.675
<.001
0.603
<.001
0.762
0.006
0.770
0.030


IGF2




0.761
0.011




IGFBP2
0.601
<.001
0.605
<.001






IGFBP5
0.702
<.001








IGFBP6
0.628
<.001


0.726
0.003




IL1B
0.676
0.002
0.716
0.004






IL6
0.688
0.005
0.766
0.044






IL6R


0.786
0.036






IL6ST
0.618
<.001
0.639
<.001
0.785
0.027
0.813
0.042


IL8
0.635
<.001
0.628
<.001






ILK
0.734
0.018
0.753
0.026






ING5
0.684
<.001
0.681
<.001
0.756
0.006




ITGA4
0.778
0.040








ITGA5
0.762
0.026








ITGA6


0.811
0.038






ITGA7
0.592
<.001
0.715
0.006
0.710
0.002




ITGAD


0.576
0.006






ITGB4


0.693
0.003






ITPR1
0.789
0.029








JUN
0.572
<.001
0.581
<.001


0.777
0.019


JUNB
0.732
0.030
0.707
0.016






KCTD12
0.758
0.036








KIT




0.691
0.009
0.738
0.028


KLC1
0.741
0.024


0.781
0.024




KLF6
0.733
0.018
0.727
0.014






KLK1


0.744
0.028






KLK2
0.697
0.002
0.679
<.001






KLK3
0.725
<.001
0.715
<.001


0.841
0.023


KRT15
0.660
<.001
0.577
<.001
0.750
0.002




KRT18
0.623
<.001
0.642
<.001
0.702
<.001
0.760
0.006


KRT2




0.740
0.044




KRT5
0.674
<.001
0.588
<.001
0.769
0.005




KRT8
0.768
0.034








L1CAM
0.737
0.036








LAG3
0.711
0.013
0.748
0.029






LAMA4




0.649
0.009




LAMB3
0.709
0.002
0.684
0.006
0.768
0.006




LGALS3
0.652
<.001
0.752
0.015
0.805
0.028




LIG3
0.728
0.016
0.667
<.001






LRP1






0.811
0.043


MDM2


0.788
0.033






MGMT
0.645
<.001
0.766
0.015






MICA
0.796
0.043
0.676
<.001






NIPPED2
0.675
<.001
0.616
<.001
0.750
0.006




MRC1






0.788
0.028


MTSS1
0.654
<.001


0.793
0.036




MYBPC1
0.706
<.001
0.534
<.001
0.773
0.004
0.692
<.001


NCAPD3
0.658
<.001
0.566
<.001
0.753
0.011
0.733
0.009


NCOR1


0.838
0.045






NEXN
0.748
0.025


0.785
0.020




NFAT5
0.531
<.001
0.626
<.001






NFATC2


0.759
0.024






OAZ1


0.766
0.024






OLFML3
0.648
<.001
0.748
0.005
0.639
<.001
0.675
<.001


OR51E2
0.823
0.034








PAGE4
0.599
<.001
0.698
0.002
0.606
<.001
0.726
<.001


PCA3
0.705
<.001
0.647
<.001






PCDHGB7






0.712
<.001


PGF
0.790
0.039








PLG






0.764
0.048


PLP2


0.766
0.037






PPAP2B
0.589
<.001
0.647
<.001
0.691
<.001
0.765
0.013


PPP1R12A
0.673
0.001
0.677
0.001


0.807
0.045


PRIMA1
0.622
<.001
0.712
0.008
0.740
0.013




PRKCA
0.637
<.001


0.694
<.001




PRKCB
0.741
0.020


0.664
<.001




PROM1
0.599
0.017
0.527
0.042
0.610
0.006
0.420
0.002


PTCH1
0.752
0.027


0.762
0.011




PTEN
0.779
0.011
0.802
0.030
0.788
0.009




PTGS2
0.639
<.001
0.606
<.001






PTHLH
0.632
0.007
0.739
0.043
0.654
0.002
0.740
0.015


PTK2B


0.775
0.019
0.831
0.028
0.810
0.017


PTPN1
0.721
0.012
0.737
0.024






PYCARD


0.702
0.005






RAB27A


0.736
0.008






RAB30
0.761
0.011








RARB


0.746
0.010






RASSF1
0.805
0.043








RHOB
0.755
0.029
0.672
0.001






RLN1
0.742
0.036
0.740
0.036






RND3
0.607
<.001
0.633
<.001






RNF114
0.782
0.041
0.747
0.013






SDC2




0.714
0.002




SDHC
0.698
<.001
0.762
0.029






SERPINA3


0.752
0.030






SERPINB5


0.669
0.014






SH3RF2
0.705
0.012
0.568
<.001


0.755
0.016


SLC22A3
0.650
<.001
0.582
<.001






SMAD4
0.636
<.001
0.684
0.002
0.741
0.007
0.738
0.007


SMARCD1
0.757
0.001








SMO
0.790
0.049




0.766
0.013


SOD1
0.741
0.037
0.713
0.007






SORBS1
0.684
0.003
0.732
0.008
0.788
0.049




SPDEF
0.840
0.012








SPINT1


0.837
0.048






SRC
0.674
<.001
0.671
<.001






SRD5A2
0.553
<.001
0.588
<.001
0.618
<.001
0.701
<.001


ST5
0.747
0.012
0.761
0.010
0.780
0.016
0.832
0.041


STAT3


0.735
0.020






STAT5A
0.731
0.005
0.743
0.009


0.817
0.027


STAT5B
0.708
<.001
0.696
0.001






SUMO1
0.815
0.037








SVIL
0.689
0.003
0.739
0.008
0.761
0.011




TBP
0.792
0.037








TFF3
0.719
0.007
0.664
0.001






TGFB1I1
0.676
0.003
0.707
0.007
0.709
0.005
0.777
0.035


TGFB2
0.741
0.010
0.785
0.017






TGFBR2




0.759
0.022




TIMP3




0.785
0.037




TMPRSS2
0.780
0.012
0.742
<.001






TNF


0.654
0.007


0.682
0.006


TNFRSF10B
0.623
<.001
0.681
<.001
0.801
0.018
0.815
0.019


TNFSF10
0.721
0.004








TP53


0.759
0.011






TP63


0.737
0.020
0.754
0.007




TPM2
0.609
<.001
0.671
<.001
0.673
<.001
0.789
0.031


TRAF3IP2
0.795
0.041
0.727
0.005






TRO
0.793
0.033
0.768
0.027
0.814
0.023




TUBB2A
0.626
<.001
0.590
<.001






VCL
0.613
<.001
0.701
0.011






VIM
0.716
0.005


0.792
0.025




WFDC1




0.824
0.029




YY1
0.668
<.001
0.787
0.014
0.716
0.001
0.819
0.011


ZFHX3
0.732
<.001
0.709
<.001






ZFP36
0.656
0.001
0.609
<.001


0.818
0.045


ZNF827
0.750
0.022









Tables 6A and 6B provide genes that were significantly associated (p<0.05), positively or negatively, with recurrence (cRFI, bRFI) after adjusting for Gleason pattern in the primary and/or highest Gleason pattern. Increased expression of genes in Table 6A is negatively associated with good prognosis, while increased expression of gene in Table 6B is positively associated with good prognosis.









TABLE 6A







Genes significantly (p < 0.05) associated with cRFI or bRFI after adjustment for


Gleason pattern in the primary Gleason pattern or highest Gleason pattern with a hazard


ratio (HR) >1.0 (increased expression is negatively associated with good prognosis)











Table 6A
cRFI
cRFI
bRFI
bRFI


Official
Primary Pattern
Highest Pattern
Primary Pattern
Highest Pattern















Symbol
HR
p-value
HR
p-value
HR
p-value
HR
p-value


















AKR1C3
1.258
0.039








ANLN
1.292
0.023


1.449
<.001
1.420
0.001


AQP2
1.178
0.008
1.287
<.001






ASAP2


1.396
0.015






ASPN
1.809
<.001
1.508
0.009
1.506
0.002
1.438
0.002


BAG5


1.367
0.012






BAX






1.234
0.044


BGN
1.465
0.009
1.342
0.046






BIRC5
1.338
0.008


1.364
0.004
1.279
0.006


BMP6
1.369
0.015
1.518
0.002






BUB1
1.239
0.024
1.227
0.001
1.236
0.004




CACNA1D


1.337
0.025






CADPS




1.280
0.029




CCNE2


1.256
0.043
1.577
<.001
1.324
0.001


CD276
1.320
0.029
1.396
0.007
1.279
0.033




CDC20
1.298
0.016
1.334
0.002
1.257
0.032
1.279
0.003


CDH7
1.258
0.047
1.338
0.013






CDKN2B
1.342
0.032
1.488
0.009






CDKN2C
1.344
0.010
1.450
<.001






CDKN3
1.284
0.012








CENPF
1.289
0.048


1.498
0.001
1.344
0.010


COL1A1
1.481
0.003
1.506
0.002






COL3A1
1.459
0.004
1.430
0.013






COL4A1
1.396
0.015








COL8A1
1.413
0.008








CRISP3
1.346
0.012
1.310
0.025






CTHRC1


1.588
0.002






DDIT4
1.363
0.020
1.379
0.028






DICER1






1.294
0.008


ENY2




1.269
0.024




FADD


1.307
0.010






FAS






1.243
0.025


FGF5
1.328
0.002








GNPTAB






1.246
0.037


GREM1
1.332
0.024
1.377
0.013
1.373
0.011




HDAC1




1.301
0.018
1.237
0.021


HSD17B4






1.277
0.011


IFN-γ




1.219
0.048




IMMT




1.230
0.049




INHBA
1.866
<.001
1.944
<.001






JAG1


1.298
0.030






KCNN2


1.378
0.020


1.282
0.017


KHDRBS3


1.353
0.029
1.305
0.014




LAMA3




1.344
<.001
1.232
0.048


LAMC1
1.396
0.015








LIMS1






1.337
0.004


LOX




1.355
0.001
1.341
0.002


LTBP2


1.304
0.045






MAGEA4
1.215
0.024








MANF




1.460
<.001




MCM6


1.287
0.042


1.214
0.046


MELK




1.329
0.002




MMP11
1.281
0.050








MRPL13






1.266
0.021


MYBL2
1.453
<.001


1.274
0.019




MYC




1.265
0.037




MY06


1.278
0.047






NET02
1.322
0.022








NFKB1






1.255
0.032


NOX4




1.266
0.041




OR51E1




1.566
<.001
1.428
0.003


PATE1
1.242
<.001
1.347
<.001


1.177
0.011


PCNA






1.251
0.025


PEX10


1.302
0.028






PGD


1.335
0.045
1.379
0.014
1.274
0.025


PIM1




1.254
0.019




PLA2G7




1.289
0.025
1.250
0.031


PLAU




1.267
0.031




PSMD13






1.333
0.005


PTK6
1.432
<.001
1.577
<.001
1.223
0.040




PTTG1




1.279
0.013
1.308
0.006


RAGE






1.329
0.011


RALA
1.363
0.044


1.471
0.003




RGS7
1.120
0.040
1.173
0.031






RRM1
1.490
0.004
1.527
<.001






SESN3


1.353
0.017






SFRP4
1.370
0.025








SHMT2
1.460
0.008
1.410
0.006
1.407
0.008
1.345
<.001


SKIL




1.307
0.025




SLC25A21




1.414
0.002
1.330
0.004


SMARCC2




1.219
0.049




SPARC


1.431
0.005






TFDP1




1.283
0.046
1.345
0.003


THBS2
1.456
0.005
1.431
0.012






TK1




1.214
0.015
1.222
0.006


TOP2A


1.367
0.018
1.518
0.001
1.480
<.001


TPX2
1.513
0.001
1.607
<.001
1.588
<.001
1.481
<.001


UBE2T
1.409
0.002


1.285
0.018




UGT2B15


1.216
0.009


1.182
0.021


XIAP




1.336
0.037
1.194
0.043
















TABLE 6B







Genes significantly (p < 0.05) associated with cRFI or bRFI after adjustment for


Gleason pattern in the primary Gleason pattern or highest Gleason pattern with hazard


ration (HR) < 1.0 (increased expression is positively associated with good prognosis)











Table 6B
cRFI
cRFI
bRFI
bRFI


Official
Primary Pattern
Highest Pattern
Primary Pattern
Highest Pattern















Symbol
HR
p-value
HR
p-value
HR
p-value
HR
p-value


















AAMP
0.660
0.001
0.675
<.001


0.836
0.045


ABCA5
0.807
0.014
0.737
<.001


0.845
0.030


ABCC1
0.780
0.038
0.794
0.015






ABCG2






0.807
0.035


ABHD2


0.720
0.002






ADH5
0.750
0.034








AKAP1


0.721
<.001






ALDH1A2
0.735
0.009
0.592
<.001
0.756
0.007
0.781
0.021


ANGPT2




0.741
0.036




ANPEP
0.637
<.001
0.536
<.001






ANXA2


0.762
0.044






APOE


0.707
0.013






APRT


0.727
0.004


0.771
0.006


ATXN1
0.725
0.013








AURKA
0.784
0.037
0.735
0.003






AXIN2
0.744
0.004
0.630
<.001






AZGP1
0.672
<.001
0.720
<.001
0.764
0.001




BAD


0.687
<.001






BAK1


0.783
0.014






BCL2
0.777
0.033
0.772
0.036






BIK


0.768
0.040






BIN1
0.691
<.001








BTRC


0.776
0.029






C7
0.707
0.004


0.791
0.024




CADM1
0.587
<.001
0.593
<.001






CASP1
0.773
0.023


0.820
0.025




CAV1




0.753
0.014




CAV2


0.627
0.009


0.682
0.003


CCL2


0.740
0.019






CCNH
0.736
0.003








CCR1


0.755
0.022






CD1A




0.740
0.025




CD44
0.590
<.001
0.637
<.001






CD68
0.757
0.026








CD82
0.778
0.012
0.759
0.016






CDC25B
0.760
0.021








CDK3
0.762
0.024


0.774
0.007




CDKN1A


0.714
0.015






CDKN1C
0.738
0.014


0.768
0.021




COL6A1
0.690
<.001
0.805
0.048






CSF1
0.675
0.002
0.779
0.036






CSK




0.825
0.004




CTNNB1
0.884
0.045


0.888
0.027




CTSB
0.740
0.017
0.676
0.003
0.755
0.010




CTSD
0.673
0.031
0.722
0.009






CTSK




0.804
0.034




CTSL2


0.748
0.019






CXCL12
0.731
0.017








CYP3A5
0.523
<.001
0.518
<.001






CYR61
0.744
0.041








DAP




0.755
0.011




DARC




0.763
0.029




DDR2






0.813
0.041


DES
0.743
0.020








DHRS9
0.606
0.001








DHX9
0.916
0.021








DIAPH1
0.749
0.036
0.688
0.003






DLGAP1
0.758
0.042
0.676
0.002






DLL4






0.779
0.010


DNIVI3
0.732
0.007








DPP4
0.732
0.004
0.750
0.014






DPT


0.704
0.014






DUSP6
0.662
<.001
0.665
0.001






EBNA1BP2






0.828
0.019


EDNRA
0.782
0.048








EGF


0.712
0.023






EGR1
0.678
0.004
0.725
0.028






EGR3
0.680
0.006
0.738
0.027






EIF2C2


0.789
0.032






EIF253






0.759
0.012


ELK4
0.745
0.024








EPHA2


0.661
0.007






EPHA3
0.781
0.026




0.828
0.037


ERBB2
0.791
0.022
0.760
0.014
0.789
0.006




ERBB3


0.757
0.009






ERCC1






0.760
0.008


ESR1


0.742
0.014






ESR2


0.711
0.038






ETV4


0.714
0.035






FAM107A
0.619
<.001
0.710
0.011


0.781
0.019


FAM13C
0.664
<.001
0.686
<.001


0.813
0.014


F AM49B
0.670
<.001
0.793
0.014
0.815
0.044
0.843
0.047


FASLG


0.616
0.004


0.813
0.038


FGF10
0.751
0.028


0.766
0.019




FGF17


0.718
0.031
0.765
0.019




FGFR2
0.740
0.009


0.738
0.002




FKBP5


0.749
0.031






FLNC




0.826
0.029




FLT1
0.779
0.045
0.729
0.006






FLT4






0.815
0.024


FOS
0.657
0.003
0.656
0.004






FSD1






0.763
0.017


FYN
0.716
0.004


0.792
0.024




GADD45B
0.692
0.009
0.697
0.010






GDF15


0.767
0.016






GHR


0.701
0.002
0.704
0.002
0.640
<.001


GNRH1




0.778
0.039




GPM6B
0.749
0.010
0.750
0.010
0.827
0.037




GRB7


0.696
0.005






GSK3B
0.726
0.005








GSN
0.660
<.001
0.752
0.019






GSTM1
0.710
0.004
0.676
<.001






GSTM2
0.643
<.001


0.767
0.015




HK1
0.798
0.035








HLA-G


0.660
0.013






HLF
0.644
<.001
0.727
0.011






HNF1B


0.755
0.013






HPS1
0.756
0.006
0.791
0.043






HSD17B10
0.737
0.006








HSD3B2






0.674
0.003


HSP90AB1


0.763
0.015






HSPB1
0.787
0.020
0.778
0.015






HSPE1


0.794
0.039






ICAM1


0.664
0.003






IER3
0.699
0.003
0.693
0.010






IFIT1
0.621
<.001
0.733
0.027






IGF1
0.751
0.017
0.655
<.001






IGFBP2
0.599
<.001
0.605
<.001






IGFBP5
0.745
0.007
0.775
0.035






IGFBP6
0.671
0.005








IL1B
0.732
0.016
0.717
0.005






IL6
0.763
0.040








IL6R


0.764
0.022






IL6ST
0.647
<.001
0.739
0.012






IL8
0.711
0.015
0.694
0.006






ING5
0.729
0.007
0.727
0.003






ITGA4


0.755
0.009






ITGA5
0.743
0.018
0.770
0.034






ITGA6
0.816
0.044
0.772
0.006






ITGA7
0.680
0.004








ITGAD


0.590
0.009






ITGB4
0.663
<.001
0.658
<.001
0.759
0.004




JUN
0.656
0.004
0.639
0.003






KIAA0196
0.737
0.011








KIT




0.730
0.021
0.724
0.008


KLC1
0.755
0.035








KLK1
0.706
0.008








KLK2
0.740
0.016
0.723
0.001






KLK3
0.765
0.006
0.740
0.002






KRT1






0.774
0.042


KRT15
0.658
<.001
0.632
<.001
0.764
0.008




KRT18
0.703
0.004
0.672
<.001
0.779
0.015
0.811
0.032


KRT5
0.686
<.001
0.629
<.001
0.802
0.023




KRT8
0.763
0.034
0.771
0.022






L1CAM
0.748
0.041








LAG3
0.693
0.008
0.724
0.020






LAMA4




0.689
0.039




LAMB3
0.667
<.001
0.645
<.001
0.773
0.006




LGALS3
0.666
<.001


0.822
0.047




LIG3


0.723
0.008






LRP1
0.777
0.041




0.769
0.007


MDM2


0.688
<.001






MET
0.709
0.010
0.736
0.028
0.715
0.003




MGMT
0.751
0.031








MICA


0.705
0.002






MPPED2
0.690
0.001
0.657
<.001
0.708
<.001




MRC1






0.812
0.049


MSH6






0.860
0.049


MTSS1
0.686
0.001








MVP
0.798
0.034
0.761
0.033






MYBPC1
0.754
0.009
0.615
<.001






NCAPD3
0.739
0.021
0.664
0.005






NEXN


0.798
0.037






NFAT5
0.596
<.001
0.732
0.005






NFATC2
0.743
0.016
0.792
0.047






NOS3
0.730
0.012
0.757
0.032






OAZ1
0.732
0.020
0.705
0.002






OCLN




0.746
0.043
0.784
0.025


OLFML3
0.711
0.002


0.709
<.001
0.720
0.001


OMD
0.729
0.011
0.762
0.033






OSM






0.813
0.028


PAGE4
0.668
0.003
0.725
0.004
0.688
<.001
0.766
0.005


PCA3
0.736
0.001
0.691
<.001






PCDHGB7




0.769
0.019
0.789
0.022


PIK3CA


0.768
0.010






PIK3CG
0.792
0.019
0.758
0.009






PLG






0.682
0.009


PPAP2B
0.688
0.005


0.815
0.046




PPP1R12A
0.731
0.026
0.775
0.042






PRIMA1
0.697
0.004
0.757
0.032






PRKCA
0.743
0.019








PRKCB
0.756
0.036


0.767
0.029




PROM1
0.640
0.027


0.699
0.034
0.503
0.013


PTCH1
0.730
0.018








PTEN
0.779
0.015


0.789
0.007




PTGS2
0.644
<.001
0.703
0.007






PTHLH
0.655
0.012
0.706
0.038
0.634
0.001
0.665
0.003


PTK2B
0.779
0.023
0.702
0.002
0.806
0.015
0.806
0.024


PYCARD


0.659
0.001






RAB30
0.779
0.033
0.754
0.014






RARB
0.787
0.043
0.742
0.009






RAS SF1
0.754
0.005








RHOA


0.796
0.041


0.819
0.048


RND3
0.721
0.011
0.743
0.028






SDC1


0.707
0.011






SDC2




0.745
0.002




SDHC
0.750
0.013








SERPINA3


0.730
0.016






SERPINB5


0.715
0.041






SH3RF2


0.698
0.025






SIPA1L1


0.796
0.014


0.820
0.004


SLC22A3
0.724
0.014
0.700
0.008






SMAD4
0.668
0.002


0.771
0.016




SMARCD1
0.726
<.001
0.700
0.001


0.812
0.028


SMO






0.785
0.027


SOD1


0.735
0.012






SORBS1


0.785
0.039






SPDEF
0.818
0.002








SPINT1
0.761
0.024
0.773
0.006






SRC
0.709
<.001
0.690
<.001






SRD5A1
0.746
0.010
0.767
0.024
0.745
0.003




SRD5A2
0.575
<.001
0.669
0.001
0.674
<.001
0.781
0.018


ST5
0.774
0.027








STAT1
0.694
0.004








STAT5A
0.719
0.004
0.765
0.006


0.834
0.049


STAT5B
0.704
0.001
0.744
0.012






SUMO1
0.777
0.014








SVIL


0.771
0.026






TBP
0.774
0.031








TFF3
0.742
0.015
0.719
0.024






TGFB1I1
0.763
0.048








TGFB2
0.729
0.011
0.758
0.002






TMPRSS2
0.810
0.034
0.692
<.001






TNF






0.727
0.022


TNFRSF10A


0.805
0.025






TNFRSF10B
0.581
<.001
0.738
0.014
0.809
0.034




TNFSF10
0.751
0.015
0.700
<.001






TP63


0.723
0.018
0.736
0.003




TPM2
0.708
0.010
0.734
0.014






TRAF3IP2


0.718
0.004






TRO


0.742
0.012






TSTA3


0.774
0.028






TUBB2A
0.659
<.001
0.650
<.001






TYMP
0.695
0.002








VCL
0.683
0.008








VIM
0.778
0.040








WDR19






0.775
0.014


XRC C 5
0.793
0.042








YY1
0.751
0.025




0.810
0.008


ZFHX3
0.760
0.005
0.726
0.001






ZFP36
0.707
0.008
0.672
0.003






ZNF827
0.667
0.002


0.792
0.039









Tables 7A and 7B provide genes significantly associated (p<0.05), positively or negatively, with clinical recurrence (cRFI) in negative TMPRSS fusion specimens in the primary or highest Gleason pattern specimen. Increased expression of genes in Table 7A is negatively associated with good prognosis, while increased expression of genes in Table 7B is positively associated with good prognosis.









TABLE 7A







Genes significantly (p < 0.05) associated with cRFI for TMPRSS2-ERG


fusion negative in the primary Gleason pattern or highest Gleason pattern


with hazard ratio (HR) > 1.0 (increased expression is negatively


associated with good prognosis)










Primary Pattern
Highest Pattern











Official Symbol
HR
p-value
HR
p-value





ANLN
1.42
0.012
1.36
0.004


AQP2
1.25
0.033




ASPN
2.48
<.001
1.65
<.001


BGN
2.04
<.001
1.45
0.007


BIRC5
1.59
<.001
1.37
0.005


BMP6
1.95
<.001
1.43
0.012


BMPR1B
1.93
0.002




BUB1
1.51
<.001
1.35
<.001


CCNE2
1.48
0.007




CD276
1.93
<.001
1.79
<.001


CDC20
1.49
0.004
1.47
<.001


CDC6
1.52
0.009
1.34
0.022


CDKN2B
1.54
0.008
1.55
0.003


CDKN2C
1.55
0.003
1.57
<.001


CDKN3
1.34
0.026




CENPF
1.63
0.002
1.33
0.018


CKS2
1.50
0.026
1.43
0.009


CLTC


1.46
0.014


COL1A1
1.98
<.001
1.50
0.002


COL3A1
2.03
<.001
1.42
0.007


COL4A1
1.81
0.002




COL8A1
1.63
0.004
1.60
0.001


CRISP3


1.31
0.016


CTHRC1
1.67
0.006
1.48
0.005


DDIT4
1.49
0.037




ENY2


1.29
0.039


EZH2


1.35
0.016


F2R
1.46
0.034
1.46
0.007


FAP
1.66
0.006
1.38
0.012


FGF5


1.46
0.001


GNPTAB
1.49
0.013




HSD17B4
1.34
0.039
1.44
0.002


INHBA
2.92
<.001
2.19
<.001


JAG1
1.38
0.042




KCNN2
1.71
0.002
1.73
<.001


KHDRBS3


1.46
0.015


KLK14
1.28
0.034




KPNA2
1.63
0.016




LAMC1
1.41
0.044




LOX


1.29
0.036


LTBP2
1.57
0.017




MELK
1.38
0.029




MMP11
1.69
0.002
1.42
0.004


MYBL2
1.78
<.001
1.49
<.001


NETO2
2.01
<.001
1.43
0.007


NME1


1.38
0.017


PATE1
1.43
<.001
1.24
0.005


PEX10
1.46
0.030




PGD
1.77
0.002




POSTN
1.49
0.037
1.34
0.026


PPFIA3
1.51
0.012




PPP3CA
1.46
0.033
1.34
0.020


PTK6
1.69
<.001
1.56
<.001


PTTG1
1.35
0.028




RAD51
1.32
0.048




RALBP1


1.29
0.042


RGS7
1.18
0.012
1.32
0.009


RRM1
1.57
0.016
1.32
0.041


RRM2
1.30
0.039




SAT1
1.61
0.007




SESN3
1.76
<.001
1.36
0.020


SFRP4
1.55
0.016
1.48
0.002


SHMT2
2.23
<.001
1.59
<.001


SPARC
1.54
0.014




SQLE
1.86
0.003




STMN1
2.14
<.001




THBS2
1.79
<.001
1.43
0.009


TK1
1.30
0.026




TOP2A
2.03
<.001
1.47
0.003


TPD52
1.63
0.003




TPX2
2.11
<.001
1.63
<.001


TRAP1
1.46
0.023




UBE2C
1.57
<.001
1.58
<.001


UBE2G1
1.56
0.008




UBE2T
1.75
<.001




UGT2B15
1.31
0.036
1.33
0.004


UHRF1
1.46
0.007




UTP23
1.52
0.017
















TABLE 7B







Genes significantly (p < 0.05) associated with cRFI for TMPRSS2-ERG


fusion negative in the primary Gleason pattern or highest Gleason pattern


with hazard ratio (HR) < 1.0 (increased expression is positively associated


with good prognosis)










Primary Pattern
Highest Pattern











Official Symbol
HR
p-value
HR
p-value





AAMP
0.56
<.001
0.65
0.001


ABCA5
0.64
<.001
0.71
<.001


ABCB1
0.62
0.004




ABCC3


0.74
0.031


ABCG2


0.78
0.050


ABHD2
0.71
0.035




ACOX2
0.54
<.001
0.71
0.007


ADH5
0.49
<.001
0.61
<.001


AKAP1
0.77
0.031
0.76
0.013


AKR1C1
0.65
0.006
0.78
0.044


AKT1


0.72
0.020


AKT3
0.75
<.001




ALDH1A2
0.53
<.001
0.60
<.001


AMPD3
0.62
<.001
0.78
0.028


ANPEP
0.54
<.001
0.61
<.001


ANXA2
0.63
0.008
0.74
0.016


ARHGAP29
0.67
0.005
0.77
0.016


ARHGDIB
0.64
0.013




ATP5J
0.57
0.050




ATXN1
0.61
0.004
0.77
0.043


AXIN2
0.51
<.001
0.62
<.001


AZGP1
0.61
<.001
0.64
<.001


BCL2
0.64
0.004
0.75
0.029


BIN1
0.52
<.001
0.74
0.010


BTG3
0.75
0.032
0.75
0.010


BTRC
0.69
0.011




C7
0.51
<.001
0.67
<.001


CADM1
0.49
<.001
0.76
0.034


CASP1
0.71
0.010
0.74
0.007


CAV1


0.73
0.015


CCL5
0.67
0.018
0.67
0.003


CCNH
0.63
<.001
0.75
0.004


CCR1


0.77
0.032


CD164
0.52
<.001
0.63
<.001


CD44
0.53
<.001
0.74
0.014


CDH10
0.69
0.040




CDH18
0.40
0.011




CDK14
0.75
0.013




CDK2


0.81
0.031


CDK3
0.73
0.022




CDKN1A
0.68
0.038




CDKN1C
0.62
0.003
0.72
0.005


COL6A1
0.54
<.001
0.70
0.004


COL6A3
0.64
0.004




CSF1
0.56
<.001
0.78
0.047


CSRP1
0.40
<.001
0.66
0.002


CTGF
0.66
0.015
0.74
0.027


CTNNB1
0.69
0.043




CTSB
0.60
0.002
0.71
0.011


CTSS
0.67
0.013




CXCL12
0.56
<.001
0.77
0.026


CYP3A5
0.43
<.001
0.63
<.001


CYR61
0.43
<.001
0.58
<.001


DAG1


0.72
0.012


DARC
0.66
0.016




DDR2
0.65
0.007




DES
0.52
<.001
0.74
0.018


DHRS9
0.54
0.007




DICER1
0.70
0.044




DLC1


0.75
0.021


DLGAP1
0.55
<.001
0.72
0.005


DNIVI3
0.61
0.001




DPP4
0.55
<.001
0.77
0.024


DPT
0.48
<.001
0.61
<.001


DUSP1
0.47
<.001
0.59
<.001


DUSP6
0.65
0.009
0.65
0.002


DYNLL1


0.74
0.045


EDNRA
0.61
0.002
0.75
0.038


EFNB2
0.71
0.043




EGR1
0.43
<.001
0.58
<.001


EGR3
0.47
<.001
0.66
<.001


EIF5


0.77
0.028


ELK4
0.49
<.001
0.72
0.012


EPHA2


0.70
0.007


EPHA3
0.62
<.001
0.72
0.009


EPHB2
0.68
0.009




ERBB2
0.64
<.001
0.63
<.001


ERBB3
0.69
0.018




ERCC1
0.69
0.019
0.77
0.021


ESR2
0.61
0.020




FAAH
0.57
<.001
0.77
0.035


FABP5
0.67
0.035




FAM107A
0.42
<.001
0.59
<.001


FAM13C
0.53
<.001
0.59
<.001


FAS
0.71
0.035




FASLG
0.56
0.017
0.67
0.014


FGF10
0.57
0.002




FGF17
0.70
0.039
0.70
0.010


FGF7
0.63
0.005
0.70
0.004


FGFR2
0.63
0.003
0.71
0.003


FKBP5


0.72
0.020


FLNA
0.48
<.001
0.74
0.022


FOS
0.45
<.001
0.56
<.001


FOXO1
0.59
<.001




FOXQ1
0.57
<.001
0.69
0.008


FYN
0.62
0.001
0.74
0.013


G6PD


0.77
0.014


GADD45A
0.73
0.045




GADD45B
0.45
<.001
0.64
0.001


GDF15
0.58
<.001




GHR
0.62
0.008
0.68
0.002


GPM6B
0.60
<.001
0.70
0.003


GSK3B
0.71
0.016
0.71
0.006


GSN
0.46
<.001
0.66
<.001


GSTM1
0.56
<.001
0.62
<.001


GSTM2
0.47
<.001
0.67
<.001


HGD


0.72
0.002


HIRIP3
0.69
0.021
0.69
0.002


HK1
0.68
0.005
0.73
0.005


HLA-G
0.54
0.024
0.65
0.013


HLF
0.41
<.001
0.68
0.001


HNF1B
0.55
<.001
0.59
<.001


HPS1
0.74
0.015
0.76
0.025


HSD17B3
0.65
0.031




HSPB2
0.62
0.004
0.76
0.027


ICAM1
0.61
0.010




IER3
0.55
<.001
0.67
0.003


IFIT1
0.57
<.001
0.70
0.008


IFNG


0.69
0.040


IGF1
0.63
<.001
0.59
<.001


IGF2
0.67
0.019
0.70
0.005


IGFBP2
0.53
<.001
0.63
<.001


IGFBP5
0.57
<.001
0.71
0.006


IGFBP6
0.41
<.001
0.71
0.012


IL10
0.59
0.020




IL1B
0.53
<.001
0.70
0.005


IL6
0.55
0.001




IL6ST
0.45
<.001
0.68
<.001


IL8
0.60
0.005
0.70
0.008


ILK
0.68
0.029
0.76
0.036


ING5
0.54
<.001
0.82
0.033


ITGA1
0.66
0.017




ITGA3
0.70
0.020




ITGA5
0.64
0.011




ITGA6
0.66
0.003
0.74
0.006


ITGA7
0.50
<.001
0.71
0.010


ITGB4
0.63
0.014
0.73
0.010


ITPR1
0.55
<.001




ITPR3


0.76
0.007


JUN
0.37
<.001
0.54
<.001


JUNB
0.58
0.002
0.71
0.016


KCTD12
0.68
0.017




KIT
0.49
0.002
0.76
0.043


KLC1
0.61
0.005
0.77
0.045


KLF 6
0.65
0.009




KLK1
0.68
0.036




KLK10


0.76
0.037


KLK2
0.64
<.001
0.73
0.006


KLK3
0.65
<.001
0.76
0.021


KLRK1
0.63
0.005




KRT15
0.52
<.001
0.58
<.001


KRT18
0.46
<.001




KRT5
0.51
<.001
0.58
<.001


KRT8
0.53
<.001




L1CAM
0.65
0.031




LAG3
0.58
0.002
0.76
0.033


LAMA4
0.52
0.018




LAMB3
0.60
0.002
0.65
0.003


LGALS3
0.52
<.001
0.71
0.002


LIG3
0.65
0.011




LRP1
0.61
0.001
0.75
0.040


MGMT
0.66
0.003




MICA
0.59
0.001
0.68
0.001


MLXIP
0.70
0.020




MMP2
0.68
0.022




MMP9
0.67
0.036




MPPED2
0.57
<.001
0.66
<.001


MRC1
0.69
0.028




MTSS1
0.63
0.005
0.79
0.037


MVP
0.62
<.001




MYBPC1
0.53
<.001
0.70
0.011


NCAM1
0.70
0.039
0.77
0.042


NCAPD3
0.52
<.001
0.59
<.001


NDRG1


0.69
0.008


NEXN
0.62
0.002




NFAT5
0.45
<.001
0.59
<.001


NFATC2
0.68
0.035
0.75
0.036


NFKBIA
0.70
0.030




NRG1
0.59
0.022
0.71
0.018


OAZ1
0.69
0.018
0.62
<.001


OLFML3
0.59
<.001
0.72
0.003


OR51E2
0.73
0.013




PAGE4
0.42
<.001
0.62
<.001


PCA3
0.53
<.001




PCDHGB7
0.70
0.032




PGF
0.68
0.027
0.71
0.013


PGR


0.76
0.041


PIK3C2A


0.80
<.001


PIK3CA
0.61
<.001
0.80
0.036


PIK3CG
0.67
0.001
0.76
0.018


PLP2
0.65
0.015
0.72
0.010


PPAP2B
0.45
<.001
0.69
0.003


PPP1R12A
0.61
0.007
0.73
0.017


PRIMA1
0.51
<.001
0.68
0.004


PRKCA
0.55
<.001
0.74
0.009


PRKCB
0.55
<.001




PROM1


0.67
0.042


PROS1
0.73
0.036




PTCH1
0.69
0.024
0.72
0.010


PTEN
0.54
<.001
0.64
<.001


PTGS2
0.48
<.001
0.55
<.001


PTH1R
0.57
0.003
0.77
0.050


PTHLH
0.55
0.010




PTK2B
0.56
<.001
0.70
0.001


PYCARD


0.73
0.009


RAB27A
0.65
0.009
0.71
0.014


RAB30
0.59
0.003
0.72
0.010


RAGE


0.76
0.011


RARB
0.59
<.001
0.63
<.001


RASSF1
0.67
0.003




RB1
0.67
0.006




RFX1
0.71
0.040
0.70
0.003


RHOA
0.71
0.038
0.65
<.001


RHOB
0.58
0.001
0.71
0.006


RND3
0.54
<.001
0.69
0.003


RNF114
0.59
0.004
0.68
0.003


SCUBE2


0.77
0.046


SDHC
0.72
0.028
0.76
0.025


SEC23A


0.75
0.029


SEMA3A
0.61
0.004
0.72
0.011


SEPT9
0.66
0.013
0.76
0.036


SERPINB5


0.75
0.039


SH3RF2
0.44
<.001
0.48
<.001


SHH


0.74
0.049


SLC22A3
0.42
<.001
0.61
<.001


SMAD4
0.45
<.001
0.66
<.001


SMARCD1
0.69
0.016




SOD1
0.68
0.042




SORBS1
0.51
<.001
0.73
0.012


SPARCL1
0.58
<.001
0.77
0.040


SPDEF
0.77
<.001




SPINT1
0.65
0.004
0.79
0.038


SRC
0.61
<.001
0.69
0.001


SRD5A2
0.39
<.001
0.55
<.001


STS
0.61
<.001
0.73
0.012


STAT1
0.64
0.006




STAT3
0.63
0.010




STAT5A
0.62
0.001
0.70
0.003


STAT5B
0.58
<.001
0.73
0.009


SUMO1
0.66
<.001




SVIL
0.57
0.001
0.74
0.022


TBP
0.65
0.002




TFF1
0.65
0.021




TFF3
0.58
<.001




TGFB1I1
0.51
<.001
0.75
0.026


TGFB2
0.48
<.001
0.62
<.001


TGFBR2
0.61
0.003




TIAM1
0.68
0.019




TIMP2
0.69
0.020




TIMP3
0.58
0.002




TNFRSF10A
0.73
0.047




TNFRSF10B
0.47
<.001
0.70
0.003


TNFSF10
0.56
0.001




TP63


0.67
0.001


TPM1
0.58
0.004
0.73
0.017


TPM2
0.46
<.001
0.70
0.005


TRA2A
0.68
0.013




TRAF3IP2
0.73
0.041
0.71
0.004


TRO
0.72
0.016
0.71
0.004


TUBB2A
0.53
<.001
0.73
0.021


TYMP
0.70
0.011




VCAM1
0.69
0.041




VCL
0.46
<.001




VEGFA


0.77
0.039


VEGFB
0.71
0.035




VIM
0.60
0.001




XRCC5


0.75
0.026


YY1
0.62
0.008
0.77
0.039


ZFHX3
0.53
<.001
0.58
<.001


ZFP36
0.43
<.001
0.54
<.001


ZNF827
0.55
0.001









Tables 8A and 8B provide genes that were significantly associated (p<0.05), positively or negatively, with clinical recurrence (cRFI) in positive TMPRSS fusion specimens in the primary or highest Gleason pattern specimen. Increased expression of genes in Table 8A is negatively associated with good prognosis, while increased expression of genes in Table 8B is positively associated with good prognosis.









TABLE 8A







Genes significantly (p < 0.05) associated with cRFI for TMPRSS2-ERG


fusion positive in the primary Gleason pattern or highest Gleason pattern


with hazard ratio (HR) > 1.0 (increased expression is negatively associated


with good prognosis)










Primary Pattern
Highest Pattern











Official Symbol
HR
p-value
HR
p-value





ACTR2
1.78
0.017




AKR1C3
1.44
0.013




ALCAM


1.44
0.022


ANLN
1.37
0.046
1.81
<.001


APOE
1.49
0.023
1.66
0.005


AQP2


1.30
0.013


ARHGMB
1.55
0.021




ASPN
2.13
<.001
2.43
<.001


ATP5E
1.69
0.013
1.58
0.014


BGN
1.92
<.001
2.55
<.001


BIRC5
1.48
0.006
1.89
<.001


BMP6
1.51
0.010
1.96
<.001


BRCA2


1.41
0.007


BUB1
1.36
0.007
1.52
<.001


CCNE2
1.55
0.004
1.59
<.001


CD276


1.65
<.001


CDC20
1.68
<.001
1.74
<.001


CDH11


1.50
0.017


CDH18
1.36
<.001




CDH7
1.54
0.009
1.46
0.026


CDKN2B
1.68
0.008
1.93
0.001


CDKN2C
2.01
<.001
1.77
<.001


CDKN3
1.51
0.002
1.33
0.049


CENPF
1.51
0.007
2.04
<.001


CKS2
1.43
0.034
1.56
0.007


COL1A1
2.23
<.001
3.04
<.001


COL1A2
1.79
0.001
2.22
<.001


COL3A1
1.96
<.001
2.81
<.001


COL4A1


1.52
0.020


COL5A1


1.50
0.020


COL5A2
1.64
0.017
1.55
0.010


COL8A1
1.96
<.001
2.38
<.001


CRISP3
1.68
0.002
1.67
0.002


CTHRC1


2.06
<.001


CTNND2
1.42
0.046
1.50
0.025


CTSK


1.43
0.049


CXCR4
1.82
0.001
1.64
0.007


DDIT4
1.54
0.016
1.58
0.009


DLL4


1.51
0.007


DYNLL1
1.50
0.021
1.22
0.002


F2R
2.27
<.001
2.02
<.001


FAP


2.12
<.001


FCGR3A


1.94
0.002


FGF5
1.23
0.047




FOXP3
1.52
0.006
1.48
0.018


GNPTAB


1.44
0.042


GPR68


1.51
0.011


GREM1
1.91
<.001
2.38
<.001


HDAC1


1.43
0.048


HDAC9
1.65
<.001
1.67
0.004


HRAS
1.65
0.005
1.58
0.021


IGFBP3
1.94
<.001
1.85
<.001


INHBA
2.03
<.001
2.64
<.001


JAG1
1.41
0.027
1.50
0.008


KCTD12


1.51
0.017


KHDRBS3
1.48
0.029
1.54
0.014


KPNA2


1.46
0.050


LAMA3
1.35
0.040




LAMC1
1.77
0.012




LTBP2


1.82
<.001


LUM
1.51
0.021
1.53
0.009


MELK
1.38
0.020
1.49
0.001


MKI67


1.37
0.014


MMP11
1.73
<.001
1.69
<.001


MRPL13


1.30
0.046


MYBL2
1.56
<.001
1.72
<.001


MYLK3


1.17
0.007


NOX4
1.58
0.005
1.96
<.001


NRIP3


1.30
0.040


NRP1


1.53
0.021


OLFML2B


1.54
0.024


OSM
1.43
0.018




PATE1
1.20
<.001
1.33
<.001


PCNA


1.64
0.003


PEX10
1.41
0.041
1.64
0.003


PIK3CA
1.38
0.037




PLK1
1.52
0.009
1.67
0.002


PLOD2


1.65
0.002


POSTN
1.79
<.001
2.06
<.001


PTK6
1.67
0.002
2.38
<.001


PTTG1
1.56
0.002
1.54
0.003


RAD21
1.61
0.036
1.53
0.005


RAD51


1.33
0.009


RALA
1.95
0.004
1.60
0.007


REG4


1.43
0.042


ROBO2
1.46
0.024




RRM1


1.44
0.033


RRM2
1.50
0.003
1.48
<.001


SAT1
1.42
0.009
1.43
0.012


SEC14L1


1.64
0.002


SFRP4
2.07
<.001
2.40
<.001


SHMT2
1.52
0.030
1.60
0.001


SLC44A1


1.42
0.039


SPARC
1.93
<.001
2.21
<.001


SULF1
1.63
0.006
2.04
<.001


THBS2
1.95
<.001
2.26
<.001


THY1
1.69
0.016
1.95
0.002


TK1


1.43
0.003


TOP2A
1.57
0.002
2.11
<.001


TPX2
1.84
<.001
2.27
<.001


UBE2C
1.41
0.011
1.44
0.006


UBE2T
1.63
0.001




UHRF1
1.51
0.007
1.69
<.001


WISP1
1.47
0.045




WNT5A
1.35
0.027
1.63
0.001


ZWINT
1.36
0.045
















TABLE 8B







Genes significantly (p < 0.05) associated with cRFI for TMPRSS2-ERG


fusion positive in the primary Gleason pattern or highest Gleason pattern


with hazard ratio (HR) < 1.0 (increased expression is positively associated


with good prognosis)










Primary Pattern
Highest Pattern











Official Symbol
HR
p-value
HR
p-value





AAMP
0.57
0.007
0.58
<.001


ABCA5


0.80
0.044


ACE
0.65
0.023
0.55
<.001


ACOX2


0.55
<.001


ADH5


0.68
0.022


AKAP1


0.81
0.043


ALDH1A2
0.72
0.036
0.43
<.001


ANPEP
0.66
0.022
0.46
<.001


APRT


0.73
0.040


AXIN2


0.60
<.001


AZGP1
0.57
<.001
0.65
<.001


BCL2


0.69
0.035


BIK
0.71
0.045




BIN1
0.71
0.004
0.71
0.009


BTRC
0.66
0.003
0.58
<.001


C7


0.64
0.006


CADM1
0.61
<.001
0.47
<.001


CCL2


0.73
0.042


CCNH
0.69
0.022




CD44
0.56
<.001
0.58
<.001


CD82


0.72
0.033


CDC25B
0.74
0.028




CDH1
0.75
0.030
0.72
0.010


CDH19


0.56
0.015


CDK3


0.78
0.045


CDKN1C
0.74
0.045
0.70
0.014


CSF1


0.72
0.037


CTSB


0.69
0.048


CTSL2


0.58
0.005


CYP3A5
0.51
<.001
0.30
<.001


DHX9
0.89
0.006
0.87
0.012


DLC1


0.64
0.023


DLGAP1
0.69
0.010
0.49
<.001


DPP4
0.64
<.001
0.56
<.001


DPT


0.63
0.003


EGR1


0.69
0.035


EGR3


0.68
0.025


EIF2S3


0.70
0.021


EIF5
0.71
0.030




ELK4
0.71
0.041
0.60
0.003


EPHA2
0.72
0.036
0.66
0.011


EPHB 4


0.65
0.007


ERCC1


0.68
0.023


ESR2


0.64
0.027


FAM107A
0.64
0.003
0.61
0.003


FAM13C
0.68
0.006
0.55
<.001


FGFR2
0.73
0.033
0.59
<.001


FKBP5


0.60
0.006


FLNC
0.68
0.024
0.65
0.012


FLT1


0.71
0.027


FOS


0.62
0.006


FOXO1


0.75
0.010


GADD45B


0.68
0.020


GHR


0.62
0.006


GPM6B


0.57
<.001


GSTM1
0.68
0.015
0.58
<.001


GSTM2
0.65
0.005
0.47
<.001


HGD
0.63
0.001
0.71
0.020


HK1
0.67
0.003
0.62
0.002


HLF


0.59
<.001


HNF1B
0.66
0.004
0.61
0.001


IER3


0.70
0.026


IGF1
0.63
0.005
0.55
<.001


IGF1R


0.76
0.049


IGFBP2
0.59
0.007
0.64
0.003


IL6ST


0.65
0.005


IL8
0.61
0.005
0.66
0.019


ILK


0.64
0.015


ING5
0.73
0.033
0.70
0.009


ITGA7
0.72
0.045
0.69
0.019


ITGB4


0.63
0.002


KLC1


0.74
0.045


KLK1
0.56
0.002
0.49
<.001


KLK10


0.68
0.013


KLK11


0.66
0.003


KLK2
0.66
0.045
0.65
0.011


KLK3
0.75
0.048
0.77
0.014


KRT15
0.71
0.017
0.50
<.001


KRT5
0.73
0.031
0.54
<.001


LAMAS


0.70
0.044


LAMB3
0.70
0.005
0.58
<.001


LGALS3


0.69
0.025


LIG3


0.68
0.022


MDK
0.69
0.035




MGMT
0.59
0.017
0.60
<.001


MGST1


0.73
0.042


MICA


0.70
0.009


MPPED2
0.72
0.031
0.54
<.001


MTSS1
0.62
0.003




MYBPC1


0.50
<.001


NCAPD3
0.62
0.007
0.38
<.001


NCOR1


0.82
0.048


NFAT5
0.60
0.001
0.62
<.001


NRG1
0.66
0.040
0.61
0.029


NUP62
0.75
0.037




OMD
0.54
<.001




PAGE4


0.64
0.005


PCA3


0.66
0.012


PCDHGB7


0.68
0.018


PGR


0.60
0.012


PPAP2B


0.62
0.010


PPP1R12A
0.73
0.031
0.58
0.003


PRIMA1


0.65
0.013


PROM1
0.41
0.013




PTCH1
0.64
0.006




PTEN


0.75
0.047


PTGS2


0.67
0.011


PTK2B


0.66
0.005


PTPN1


0.71
0.026


RAGE
0.70
0.012




RARB


0.68
0.016


RGS10


0.84
0.034


RHOB


0.66
0.016


RND3


0.63
0.004


SDHC
0.73
0.044
0.69
0.016


SERPINA3
0.67
0.011
0.51
<.001


SERPINB5


0.42
<.001


SH3RF2
0.66
0.012
0.51
<.001


SLC22A3
0.59
0.003
0.48
<.001


SMAD4
0.64
0.004
0.49
<.001


SMARCC2


0.73
0.042


SMARCD1
0.73
<.001
0.76
0.035


SMO


0.64
0.006


SNAI1


0.53
0.008


SOD1


0.60
0.003


SRC
0.64
<.001
0.61
<.001


SRD5A2
0.63
0.004
0.59
<.001


STAT3


0.64
0.014


STAT5A


0.70
0.032


STAT5B
0.74
0.034
0.63
0.003


SVIL


0.71
0.028


TGFB1I1


0.68
0.036


TMPRSS2
0.72
0.015
0.67
<.001


TNFRSF10A


0.69
0.010


TNFRSF10B
0.67
0.007
0.64
0.001


TNFRSF18
0.38
0.003




TNFSF10


0.71
0.025


TP53
0.68
0.004
0.57
<.001


TP63
0.75
0.049
0.52
<.001


TPM2


0.62
0.007


TRAF3IP2
0.71
0.017
0.68
0.005


TRO


0.72
0.033


TUBB2A


0.69
0.038


VCL


0.62
<.001


VEGFA


0.71
0.037


WWOX


0.65
0.004


ZFHX3
0.77
0.011
0.73
0.012


ZFP36


0.69
0.018


ZNF827
0.68
0.013
0.49
<.001









Tables 9A and 9B provide genes significantly associated (p<0.05), positively or negatively, with TMPRSS fusion status in the primary Gleason pattern. Increased expression of genes in Table 9A are positively associated with TMPRSS fusion positivity, while increased expression of genes in Table 10A are negatively associated with TMPRSS fusion positivity.









TABLE 9A







Genes significantly (p < 0.05) associated with TMPRSS fusion status


in the primary Gleason pattern with odds ratio (OR) > 1.0 (increased


expression is positively associated with TMPRSS fusion positivity









Official Symbol
p-value
Odds Ratio





ABCC8
<.001
1.86


ALDH18A1
0.005
1.49


ALKBH3
0.043
1.30


ALOX5
<.001
1.66


AMPD3
<.001
3.92


APEX1
<.001
2.00


ARHGD113
<.001
1.87


ASAP2
0.019
1.48


ATXN1
0.013
1.41


BMPR1B
<.001
2.37


CACNA1D
<.001
9.01


CADPS
0.015
1.39


CD276
0.003
2.25


CDH1
0.016
1.37


CDH7
<.001
2.22


CDK7
0.025
1.43


COL9A2
<.001
2.58


CRISP3
<.001
2.60


CTNND1
0.033
1.48


ECE1
<.001
2.22


EIF5
0.023
1.34


EPHB4
0.005
1.51


ERG
<.001
14.5


FAM171B
0.047
1.32


FAM73A
0.008
1.45


FASN
0.004
1.50


GNPTAB
<.001
1.60


GPS1
0.006
1.45


GRB7
0.023
1.38


HDAC1
<.001
4.95


HGD
<.001
1.64


HIP1
<.001
1.90


HNF1B
<.001
3.55


HSPA8
0.041
1.32


IGF1R
0.001
1.73


ILF3
<.001
1.91


IMMT
0.025
1.36


ITPR1
<.001
2.72


ITPR3
<.001
5.91


JAG1
0.007
1.42


KCNN2
<.001
2.80


KHDRBS3
<.001
2.63


KIAA0247
0.019
1.38


KLK11
<.001
1.98


LAMC1
0.008
1.56


LAMC2
<.001
3.30


LOX
0.009
1.41


LRP1
0.044
1.30


MAP3K5
<.001
2.06


MAP7
<.001
2.74


MSH2
0.005
1.59


MSH3
0.006
1.45


MUC1
0.012
1.42


MYO6
<.001
3.79


NCOR2
0.001
1.62


NDRG1
<.001
6.77


NETO2
<.001
2.63


ODC1
<.001
1.98


OR51E1
<.001
2.24


PDE9A
<.001
2.21


PEX10
<.001
3.41


PGK1
0.022
1.33


PLA2G7
<.001
5.51


PPP3CA
0.047
1.38


PSCA
0.013
1.43


PSMD13
0.004
1.51


PTCH1
0.022
1.38


PTK2
0.014
1.38


PTK6
<.001
2.29


PTK7
<.001
2.45


PTPRK
<.001
1.80


RAB30
0.001
1.60


REG4
0.018
1.58


RELA
0.001
1.62


RFX1
0.020
1.43


RGS10
<.001
1.71


SCUBE2
0.009
1.48


SEPT9
<.001
3.91


SH3RF2
0.004
1.48


SH3YL1
<.001
1.87


SHH
<.001
2.45


SIM2
<.001
1.74


SIPA1L1
0.021
1.35


SLC22A3
<.001
1.63


SLC44A1
<.001
1.65


SPINT1
0.017
1.39


TFDP1
0.005
1.75


TMPRSS2ERGA
0.002
14E5


TMPRSS2ERGB
<.001
1.97


TRIM14
<.001
1.65


TSTA3
0.018
1.38


UAP1
0.046
1.39


UBE2G1
0.001
1.66


UGDH
<.001
2.22


XRCCS
<.001
1.66


ZMYND8
<.001
2.19
















TABLE 9B







Genes significantly (p < 0.05) associated with TMPRSS fusion status


in the primary Gleason pattern with odds ratio (OR) < 1.0 (increased


expression is negatively associated with TMPRSS fusion positivity)









Official Symbol
p-value
Odds Ratio





ABCC4
0.045
0.77


ABHD2
<.001
0.38


ACTR2
0.027
0.73


ADAMTS1
0.024
0.58


ADH5
<.001
0.58


AGTR2
0.016
0.64


AKAP1
0.013
0.70


AKT2
0.015
0.71


ALCAM
<.001
0.45


ALDH1A2
0.004
0.70


ANPEP
<.001
0.43


ANXA2
0.010
0.71


APC
0.036
0.73


APOC1
0.002
0.56


APOE
<.001
0.44


ARF1
0.041
0.77


ATM
0.036
0.74


AURKB
<.001
0.62


AZGP1
<.001
0.54


BBC3
0.030
0.74


BCL2
0.012
0.70


BIN1
0.021
0.74


BTG1
0.004
0.67


BTG3
0.003
0.63


C7
0.023
0.74


CADM1
0.007
0.69


CASP1
0.011
0.70


CAV1
0.011
0.71


CCND1
0.019
0.72


CCR1
0.022
0.73


CD44
<.001
0.57


CD68
<.001
0.54


CD82
0.002
0.66


CDH5
0.007
0.66


CDKN1A
<.001
0.60


CDKN2B
<.001
0.54


CDKN2C
0.012
0.72


CDKN3
0.037
0.77


CHN1
0.038
0.75


CKS2
<.001
0.48


COL11A1
0.017
0.72


COL1A1
<.001
0.59


COL1A2
0.001
0.62


COL3A1
0.027
0.73


COL4A1
0.043
0.76


COL5A1
0.039
0.74


COL5A2
0.026
0.73


COL6A1
0.008
0.66


COL6A3
<.001
0.59


COL8A1
0.022
0.74


CSF1
0.011
0.70


CTNNB1
0.021
0.69


CTSB
<.001
0.62


CTSD
0.036
0.68


CTSK
0.007
0.70


CTSS
0.002
0.64


CXCL12
<.001
0.48


CXCR4
0.005
0.68


CXCR7
0.046
0.76


CYR61
0.004
0.65


DAP
0.002
0.64


DARC
0.021
0.73


DDR2
0.021
0.73


DHRS9
<.001
0.52


DIAPH1
<.001
0.56


DICER1
0.029
0.75


DLC1
0.013
0.72


DLGAP1
<.001
0.60


DLL4
<.001
0.57


DPT
0.006
0.68


DUSP1
0.012
0.68


DUSP6
0.001
0.62


DVL1
0.037
0.75


EFNB2
<.001
0.32


EGR1
0.003
0.65


ELK4
<.001
0.60


ERBB2
<.001
0.61


ERBB3
0.045
0.76


ESR2
0.010
0.70


ETV1
0.042
0.74


FABP5
<.001
0.21


FAM13C
0.006
0.67


FCGR3A
0.018
0.72


FGF17
0.009
0.71


FGF6
0.011
0.70


FGF7
0.003
0.63


FN1
0.006
0.69


FOS
0.035
0.74


FOXP3
0.010
0.71


GABRG2
0.029
0.74


GADD45B
0.003
0.63


GDF15
<.001
0.54


GPM6B
0.004
0.67


GPNMB
0.001
0.62


GSN
0.009
0.69


HLA-G
0.050
0.74


HLF
0.018
0.74


HPS1
<.001
0.48


HSD17B3
0.003
0.60


HSD17B4
<.001
0.56


HSPB1
<.001
0.38


HSPB2
0.002
0.62


IFI30
0.049
0.75


IFNG
0.006
0.64


IGF1
0.016
0.73


IGF2
0.001
0.57


IGFBP2
<.001
0.51


IGFBP3
<.001
0.59


IGFBP6
<.001
0.57


IL10
<.001
0.62


IL17A
0.012
0.63


IL1A
0.011
0.59


IL2
0.001
0.63


IL6ST
<.001
0.52


INSL4
0.014
0.71


ITGA1
0.009
0.69


ITGA4
0.007
0.68


JUN
<.001
0.59


KIT
<.001
0.64


KRT76
0.016
0.70


LAG3
0.002
0.63


LAPTM5
<.001
0.58


LGALS3
<.001
0.53


LTBP2
0.011
0.71


LUM
0.012
0.70


MAOA
0.020
0.73


MAP4K4
0.007
0.68


MGST1
<.001
0.54


MMP2
<.001
0.61


MPPED2
<.001
0.45


MRC1
0.005
0.67


MTPN
0.002
0.56


MTSS1
<.001
0.53


MVP
0.009
0.72


MYBPC1
<.001
0.51


MYLK3
0.001
0.58


NCAM1
<.001
0.59


NCAPD3
<.001
0.40


NCOR1
0.004
0.69


NFKBIA
<.001
0.63


NNMT
0.006
0.66


NPBWR1
0.027
0.67


OAZ1
0.049
0.64


OLFML3
<.001
0.56


OSM
<.001
0.64


PAGE1
0.012
0.52


PDGFRB
0.016
0.73


PECAM1
<.001
0.55


PGR
0.048
0.77


PIK3CA
<.001
0.55


PIK3CG
0.008
0.71


PLAU
0.044
0.76


PLK1
0.006
0.68


PLOD2
0.013
0.71


PLP2
0.024
0.73


PNLIPRP2
0.009
0.70


PPAP2B
<.001
0.62


PRKAR2B
<.001
0.61


PRKCB
0.044
0.76


PROS1
0.005
0.67


PTEN
<.001
0.47


PTGER3
0.007
0.69


PTH1R
0.011
0.70


PTK2B
<.001
0.61


PTPN1
0.028
0.73


RAB27A
<.001
0.21


RAD51
<.001
0.51


RAD9A
0.030
0.75


RARB
<.001
0.62


RASSF1
0.038
0.76


RECK
0.009
0.62


RHOB
0.004
0.64


RHOC
<.001
0.56


RLN1
<.001
0.30


RND3
0.014
0.72


S100P
0.002
0.66


SDC2
<.001
0.61


SEMA3A
0.001
0.64


SMAD4
<.001
0.64


SPARC
<.001
0.59


SPARCL1
<.001
0.56


SPINK1
<.001
0.26


SRD5A1
0.039
0.76


STAT1
0.026
0.74


STS
0.006
0.64


SULF1
<.001
0.53


TFF3
<.001
0.19


TGFA
0.002
0.65


TGFB1I1
0.040
0.77


TGFB2
0.003
0.66


TGFB3
<.001
0.54


TGFBR2
<.001
0.61


THY1
<.001
0.63


TIMP2
0.004
0.66


TIMP3
<.001
0.60


TMPRSS2
<.001
0.40


TNFSF11
0.026
0.63


TPD52
0.002
0.64


TRAM1
<.001
0.45


TRPC6
0.002
0.64


TUBB2A
<.001
0.49


VCL
<.001
0.57


VEGFB
0.033
0.73


VEGFC
<.001
0.61


VIM
0.012
0.69


WISP1
0.030
0.75


WNT5A
<.001
0.50









A molecular field effect was investigated, and determined that the expression levels of histologically normal-appearing cells adjacent to the tumor exhibited a molecular signature of prostate cancer. Tables 10A and 10B provide genes significantly associated (p<0.05), positively or negatively, with cRFI or bRFI in non-tumor samples. Table 10A is negatively associated with good prognosis, while increased expression of genes in Table 10B is positively associated with good prognosis.









TABLE 10A







Genes significantly (p < 0.05) associated with cRFI


or bRFI in Non-Tumor Samples with hazard ratio


(HR) > 1.0 (increased expression is negatively


associated with good prognosis)









Official
cRFI
bRFI











Symbol
HR
p-value
HR
p-value














ALCAM


1.278
0.036


ASPN
1.309
0.032




BAG5
1.458
0.004




BRCA2
1.385
<.001




CACNA1D


1.329
0.035


CD164


1.339
0.020


CDKN2B
1.398
0.014




COL3A1
1.300
0.035




COL4A1
1.358
0.019




CTNND2


1.370
0.001


DARC
1.451
0.003




DICER1


1.345
<.001


DPP4


1.358
0.008


EFNB2


1.323
0.007


FASN


1.327
0.035


GHR


1.332
0.048


HSPA5


1.260
0.048


INHBA
1.558
<.001




KCNN2


1.264
0.045


KRT76


1.115
<.001


LAMC1
1.390
0.014




LAMC2


1.216
0.042


LIG3


1.313
0.030


MAOA


1.405
0.013


MCM6
1.307
0.036




MKI67
1.271
0.008




NEK2


1.312
0.016


NPBWR1
1.278
0.035




ODC1


1.320
0.010


PEX10


1.361
0.014


PGK1
1.488
0.004




PLA2G7


1.337
0.025


POSTN
1.306
0.043




PTK6


1.344
0.005


REG4


1.348
0.009


RGS7


1.144
0.047


SFRP4
1.394
0.009




TARP


1.412
0.011


TFF1


1.346
0.010


TGFBR2
1.310
0.035




THY1
1.300
0.038




TMPRSS2ERGA


1.333
<.001


TPD52


1.374
0.015


TRPC6
1.272
0.046




UBE2C
1.323
0.007




UHRF1
1.325
0.021
















TABLE 10B







Genes significantly (p < 0.05) associated with cRFI


or bRFI in Non-Tumor Samples with hazard ratio


(HR) < 1.0 (increased expression is positively


associated with good prognosis)











Official
cRFI
bRFI













Symbol
HR
p-value
HR
p-value

















ABCA5
0.807
0.028





ABCC3
0.760
0.019
0.750
0.003



ABHD2
0.781
0.028





ADAM15
0.718
0.005





AKAP1
0.740
0.009





AMPD3


0.793
0.013



ANGPT2


0.752
0.027



ANXA2


0.776
0.035



APC
0.755
0.014





APRT
0.762
0.025





AR
0.752
0.015





ARHGDIB


0.753
<.001



BIN1
0.738
0.016





CADM1
0.711
0.004





CCNH
0.820
0.041





CCR1


0.749
0.007



CDK14


0.772
0.014



CDK3
0.819
0.044





CDKN1C
0.808
0.038





CHAF1A
0.634
0.002
0.779
0.045



CHN1


0.803
0.034



CHRAC1
0.751
0.014
0.779
0.021



COL5A1


0.736
0.012



COL5A2


0.762
0.013



COL6A1


0.757
0.032



COL6A3


0.757
0.019



CSK
0.663
<.001
0.698
<.001



CTSK


0.782
0.029



CXCL12


0.771
0.037



CXCR7


0.753
0.008



CYP3A5
0.790
0.035





DDIT4


0.725
0.017



DIAPH1


0.771
0.015



DLC1
0.744
0.004
0.807
0.015



DLGAP1
0.708
0.004





DUSP1
0.740
0.034





EDN1


0.742
0.010



EGR1
0.731
0.028





EIF3H
0.761
0.024





EIF4E
0.786
0.041





ERBB2
0.664
0.001





ERBB4
0.764
0.036





ERCC1
0.804
0.041





ESR2


0.757
0.025



EZH2


0.798
0.048



FAAH
0.798
0.042





FAM13C
0.764
0.012





FAM171B


0.755
0.005



FAM49B


0.811
0.043



FAM73A
0.778
0.015





FASLG


0.757
0.041



FGFR2
0.735
0.016





FOS
0.690
0.008





FYN
0.788
0.035
0.777
0.011



GPNMB


0.762
0.011



GSK3B
0.792
0.038





HGD
0.774
0.017





HIRIP3
0.802
0.033





HSP90AB1
0.753
0.013





HSPB1
0.764
0.021





HSPE1
0.668
0.001





IFI30


0.732
0.002



IGF2


0.747
0.006



IGFBP5


0.691
0.006



IL6ST


0.748
0.010



IL8


0.785
0.028



IMMT


0.708
<.001



ITGA6
0.747
0.008





ITGAV


0.792
0.016



ITGB3


0.814
0.034



ITPR3
0.769
0.009





JUN
0.655
0.005





KHDRBS3


0.764
0.012



KLF6
0.714
<.001





KLK2
0.813
0.048





LAMA4


0.702
0.009



LAMA5
0.744
0.011





LAPTM5


0.740
0.009



LGALS3
0.773
0.036
0.788
0.024



LIMS1


0.807
0.012



MAP3K5


0.815
0.034



MAP3K7


0.809
0.032



MAP4K4
0.735
0.018
0.761
0.010



MAPKAPK3
0.754
0.014





MICA
0.785
0.019





MTA1


0.808
0.043



MVP


0.691
0.001



MYLK3


0.730
0.039



MYO6
0.780
0.037





NCOA1


0.787
0.040



NCOR1


0.876
0.020



NDRG1
0.761
<.001





NFAT5
0.770
0.032





NFKBIA


0.799
0.018



NME2


0.753
0.005



NUP62


0.842
0.032



OAZ1


0.803
0.043



OLFML2B


0.745
0.023



OLFML3


0.743
0.009



OSM


0.726
0.018



PCA3
0.714
0.019





PECAM1


0.774
0.023



PIK3C2A


0.768
0.001



PIM1
0.725
0.011





PLOD2


0.713
0.008



PPP3CA
0.768
0.040





PROM1


0.482
<.001



PTEN


0.807
0.012



PTGS2
0.726
0.011





PTTG1


0.729
0.006



PYCARD


0.783
0.012



RAB30


0.730
0.002



RAGE
0.792
0.012





RFX1
0.789
0.016
0.792
0.010



RGS10
0.781
0.017





RUNX1


0.747
0.007



SDHC


0.827
0.036



SEC23A


0.752
0.010



SEPT9


0.889
0.006



SERPINA3


0.738
0.013



SLC25A21


0.788
0.045



SMARCD1
0.788
0.010
0.733
0.007



SMO
0.813
0.035





SRC
0.758
0.026





SRD5A2


0.738
0.005



ST5


0.767
0.022



STAT5A


0.784
0.039



TGFB2
0.771
0.027





TGFB3


0.752
0.036



THBS2


0.751
0.015



TNFRSF10B
0.739
0.010





TPX2


0.754
0.023



TRAF3IP2


0.774
0.015



TRAM1
0.868
<.001
0.880
<.001



TRIM14
0.785
0.047





TUBB2A
0.705
0.010





TYMP


0.778
0.024



UAP1
0.721
0.013





UTP23
0.763
0.007
0.826
0.018



VCL


0.837
0.040



VEGFA
0.755
0.009





WDR19
0.724
0.005





YBX1


0.786
0.027



ZFP36
0.744
0.032





ZNF827
0.770
0.043










Table 11 provides genes that are significantly associated (p<0.05) with cRFI or bRFI after adjustment for Gleason pattern or highest Gleason pattern.









TABLE 11







Genes significantly (p < 0.05) associated with


cRFI or bRFI after adjustment for Gleason


pattern in the primary Gleason pattern or highest


Gleason pattern Some HR <= 1.0 and some HR >1.0










TABLE 11
cRFI
bRFI
bRFI


Official
Highest Pattern
Primary Pattern
Highest Pattern













Symbol
HR
p-value
HR
p-value
HR
p-value





HSPA5
0.710
0.009
1.288
0.030




ODC1
0.741
0.026
1.343
0.004
1.261
0.046









Tables 12A and 12B provide genes that are significantly associated (p<0.05) with prostate cancer specific survival (PCSS) in the primary Gleason pattern. Increased expression of genes in Table 12A is negatively associated with good prognosis, while increased expression of genes in Table 12B is positively associated with good prognosis.









TABLE 12A







Genes significantly (p < 0.05)


associated with prostate cancer


specific survival (PCSS) in the


Primary Gleason Pattern HR > 1.0


(Increased expression is negatively


associated with good prognosis)











Official





Symbol
HR
p-value















AKR1C3
1.476
0.016



ANLN
1.517
0.006



APOC1
1.285
0.016



APOE
1.490
0.024



ASPN
3.055
<.001



ATP5E
1.788
0.012



AURKB
1.439
0.008



BGN
2.640
<.001



BIRC5
1.611
<.001



BMP6
1.490
0.021



BRCA1
1.418
0.036



CCNB1
1.497
0.021



CD276
1.668
0.005



CDC20
1.730
<.001



CDH11
1.565
0.017



CDH7
1.553
0.007



CDKN2B
1.751
0.003



CDKN2C
1.993
0.013



CDKN3
1.404
0.008



CENPF
2.031
<.001



CHAF1A
1.376
0.011



CKS2
1.499
0.031



COL1A1
2.574
<.001



COL1A2
1.607
0.011



COL3A1
2.382
<.001



COL4A1
1.970
<.001



COL5A2
1.938
0.002



COL8A1
2.245
<.001



CTHRC1
2.085
<.001



CXCR4
1.783
0.007



DDIT4
1.535
0.030



DYNLL1
1.719
0.001



F2R
2.169
<.001



FAM171B
1.430
0.044



FAP
1.993
0.002



FCGR3A
2.099
<.001



FN1
1.537
0.024



GPR68
1.520
0.018



GREM1
1.942
<.001



IFI30
1.482
0.048



IGFBP3
1.513
0.027



INHBA
3.060
<.001



KIF4A
1.355
0.001



KLK14
1.187
0.004



LAPTM5
1.613
0.006



LTBP2
2.018
<.001



MMP11
1.869
<.001



MYBL2
1.737
0.013



NEK2
1.445
0.028



NOX4
2.049
<.001



OLFML2B
1.497
0.023



PLK1
1.603
0.006



POSTN
2.585
<.001



PPFIA3
1.502
0.012



PTK6
1.527
0.009



PTTG1
1.382
0.029



RAD51
1.304
0.031



RGS7
1.251
<.001



RRM2
1.515
<.001



SAT1
1.607
0.004



SDC1
1.710
0.007



SESN3
1.399
0.045



SFRP4
2.384
<.001



SHMT2
1.949
0.003



SPARC
2.249
<.001



STMN1
1.748
0.021



SULF1
1.803
0.004



THBS2
2.576
<.001



THY1
1.908
0.001



TK1
1.394
0.004



TOP2A
2.119
<.001



TPX2
2.074
0.042



UBE2C
1.598
<.001



UGT2B15
1.363
0.016



UHRF1
1.642
0.001



ZWINT
1.570
0.010

















TABLE 12B







Genes significantly (p < 0.05)


associated with prostate cancer


specific survival (PCSS) in


the Primary Gleason


Pattern HR < 1.0 (Increased


expression is positively


associated with good prognosis)











Official





Symbol
HR
p-value







AAMP
0.649
0.040



ABCA5
0.777
0.015



ABCG2
0.715
0.037



ACOX2
0.673
0.016



ADH5
0.522
<.001



ALDH1A2
0.561
<.001



AMACR
0.693
0.029



AMPD3
0.750
0.049



ANPEP
0.531
<.001



ATXN1
0.640
0.011



AXIN2
0.657
0.002



AZGP1
0.617
<.001



BDKRB1
0.553
0.032



BIN1
0.658
<.001



BTRC
0.716
0.011



C7
0.531
<.001



CADM1
0.646
0.015



CASP7
0.538
0.029



CCNH
0.674
0.001



CD164
0.606
<.001



CD44
0.687
0.016



CDK3
0.733
0.039



CHN1
0.653
0.014



COL6A1
0.681
0.015



CSF1
0.675
0.019



CSRP1
0.711
0.007



CXCL12
0.650
0.015



CYP3A5
0.507
<.001



CYR61
0.569
0.007



DLGAP1
0.654
0.004



DNM3
0.692
0.010



DPP4
0.544
<.001



DPT
0.543
<.001



DUSP1
0.660
0.050



DUSP6
0.699
0.033



EGR1
0.490
<.001



EGR3
0.561
<.001



EIF5
0.720
0.035



ERBB3
0.739
0.042



FAAH
0.636
0.010



FAM107A
0.541
<.001



FAM13C
0.526
<.001



FAS
0.689
0.030



FGF10
0.657
0.024



FKBP5
0.699
0.040



FLNC
0.742
0.036



FOS
0.556
0.005



FOXQ1
0.666
0.007



GADD45B
0.554
0.002



GDF15
0.659
0.009



GHR
0.683
0.027



GPM6B
0.666
0.005



GSN
0.646
0.006



GSTM1
0.672
0.006



GSTM2
0.514
<.001



HGD
0.771
0.039



HIRIP3
0.730
0.013



HK1
0.778
0.048



HLF
0.581
<.001



HNF1B
0.643
0.013



HSD17B10
0.742
0.029



IER3
0.717
0.049



IGF1
0.612
<.001



IGFBP6
0.578
0.003



IL2
0.528
0.010



IL6ST
0.574
<.001



IL8
0.540
0.001



ING5
0.688
0.015



ITGA6
0.710
0.005



ITGA7
0.676
0.033



JUN
0.506
0.001



KIT
0.628
0.047



KLK1
0.523
0.002



KLK2
0.581
<.001



KLK3
0.676
<.001



KRT15
0.684
0.005



KRT18
0.536
<.001



KRT5
0.673
0.004



KRT8
0.613
0.006



LAMB3
0.740
0.027



LGALS3
0.678
0.007



MGST1
0.640
0.002



MPPED2
0.629
<.001



MTSS1
0.705
0.041



MYBPC1
0.534
<.001



NCAPD3
0.519
<.001



NFAT5
0.536
<.001



NRG1
0.467
0.007



OLFML3
0.646
0.001



OMD
0.630
0.006



OR51E2
0.762
0.017



PAGE4
0.518
<.001



PCA3
0.581
<.001



PGF
0.705
0.038



PPAP2B
0.568
<.001



PPP1R12A
0.694
0.017



PRIMA1
0.678
0.014



PRKCA
0.632
0.001



PRKCB
0.692
0.028



PROM1
0.393
0.017



PTEN
0.689
0.002



PTGS2
0.611
0.004



PTH1R
0.629
0.031



RAB27A
0.721
0.046



RND3
0.678
0.029



RNF114
0.714
0.035



SDHC
0.590
<.001



SERPINA3
0.710
0.050



SH3RF2
0.570
0.005



SLC22A3
0.517
<.001



SMAD4
0.528
<.001



SMO
0.751
0.026



SRC
0.667
0.004



SRD5A2
0.488
<.001



STAT5B
0.700
0.040



SVIL
0.694
0.024



TFF3
0.701
0.045



TGFB1I1
0.670
0.029



TGFB2
0.646
0.010



TNFRSF10B
0.685
0.014



TNFSF10
0.532
<.001



TPM2
0.623
0.005



TRO
0.767
0.049



TUBB2A
0.613
0.003



VEGFB
0.780
0.034



ZFP36
0.576
0.001



ZNF827
0.644
0.014










Analysis of gene expression and upgrading/upstaging was based on univariate ordinal logistic regression models using weighted maximum likelihood estimators for each gene in the gene list (727 test genes and 5 reference genes). P-values were generated using a Wald test of the null hypothesis that the odds ratio (OR) is one. Both unadjusted p-values and the q-value (smallest FDR at which the hypothesis test in question is rejected) were reported. Un-adjusted p-values <0.05 were considered statistically significant. Since two tumor specimens were selected for each patient, this analysis was performed using the 2 specimens from each patient as follows: (1) analysis using the primary Gleason pattern specimen from each patient (Specimens A1 and B2 as described in Table 2); and (2) analysis using the highest Gleason pattern specimen from each patient (Specimens A1 and B1 as described in Table 2). 200 genes were found to be significantly associated (p<0.05) with upgrading/upstaging in the primary Gleason pattern sample (PGP) and 203 genes were found to be significantly associated (p<0.05) with upgrading/upstaging in the highest Gleason pattern sample (HGP).


Tables 13A and 13B provide genes significantly associated (p<0.05), positively or negatively, with upgrading/upstaging in the primary and/or highest Gleason pattern. Increased expression of genes in Table 13A is positively associated with higher risk of upgrading/upstaging (poor prognosis), while increased expression of genes in Table 13B is negatively associated with risk of upgrading/upstaging (good prognosis).









TABLE 13A







Genes significantly (p < 0.05) associated with


upgrading/upstaging in the Primary Gleason


Pattern (PGP) and Highest Gleason Pattern


(HGP) OR > 1.0 (Increased expression is


positively associated with higher risk of


upgrading/upstaging (poor prognosis))










PGP
HGP











Gene
OR
p-value
OR
p-value





ALCAM
1.52
0.0179
1.50
0.0184


ANLN
1.36
0.0451
 .
 .


APOE
1.42
0.0278
1.50
0.0140


ASPN
1.60
0.0027
2.06
0.0001


AURKA
1.47
0.0108
 .
 .


AURKB
 .
 .
1.52
0.0070


BAX
 .
 .
1.48
0.0095


BGN
1.58
0.0095
1.73
0.0034


BIRC5
1.38
0.0415
 .
 .


BMP6
1.51
0.0091
1.59
0.0071


BUB1
1.38
0.0471
1.59
0.0068


CACNA1D
1.36
0.0474
1.52
0.0078


CASP7
 .
 .
1.32
0.0450


CCNE2
1.54
0.0042
 .
 .


CD276
 .
 .
1.44
0.0265


CDC20
1.35
0.0445
1.39
0.0225


CDKN2B
 .
 .
1.36
0.0415


CENPF
1.43
0.0172
1.48
0.0102


CLTC
1.59
0.0031
1.57
0.0038


COL1A1
1.58
0.0045
1.75
0.0008


COL3A1
1.45
0.0143
1.47
0.0131


COL8A1
1.40
0.0292
1.43
0.0258


CRISP3
 .
 .
1.40
0.0256


CTHRC1
 .
 .
1.56
0.0092


DBN1
1.43
0.0323
1.45
0.0163


DIAPH1
1.51
0.0088
1.58
0.0025


DICER1
 .
 .
1.40
0.0293


DIO2
 .
 .
1.49
0.0097


DVL1
 .
 .
1.53
0.0160


F2R
1.46
0.0346
1.63
0.0024


FAP
1.47
0.0136
1.74
0.0005


FCGR3A
 .
 .
1.42
0.0221


HPN
 .
 .
1.36
0.0468


HSD17B4
 .
 .
1.47
0.0151


HSPA8
1.65
0.0060
1.58
0.0074


IL11
1.50
0.0100
1.48
0.0113


IL1B
1.41
0.0359
 .
 .


INHBA
1.56
0.0064
1.71
0.0042


KHDRBS3
1.43
0.0219
1.59
0.0045


KIF4A
 .
 .
1.50
0.0209


KPNA2
1.40
0.0366
 .
 .


KRT2
 .
 .
1.37
0.0456


KRT75
 .
 .
1.44
0.0389


MANF
 .
 .
1.39
0.0429


MELK
1.74
0.0016
 .
 .


MKI67
1.35
0.0408
 .
 .


MMP11
 .
 .
1.56
0.0057


NOX4
1.49
0.0105
1.49
0.0138


PLAUR
1.44
0.0185
 .
 .


PLK1
 .
 .
1.41
0.0246


PTK6
 .
 .
1.36
0.0391


RAD51
 .
 .
1.39
0.0300


RAF1
 .
 .
1.58
0.0036


RRM2
1.57
0.0080
 .
 .


SESN3
1.33
0.0465
 .
 .


SFRP4
2.33
<0.0001
2.51
0.0015


SKIL
1.44
0.0288
1.40
0.0368


SOX4
1.50
0.0087
1.59
0.0022


SPINK1
1.52
0.0058
 .
 .


SPP1
 .
 .
1.42
0.0224


THBS2
 .
 .
1.36
0.0461


TK1
 .
 .
1.38
0.0283


TOP2A
1.85
0.0001
1.66
0.0011


TPD52
1.78
0.0003
1.64
0.0041


TPX2
1.70
0.0010
 .
 .


UBE2G1
1.38
0.0491
 .
 .


UBE2T
1.37
0.0425
1.46
0.0162


UHRF1
 .
 .
1.43
0.0164


VCPIP1
 .
 .
1.37
0.0458
















TABLE 13B







Genes significantly (p < 0.05) associated with


upgrading/upstaging in the Primary Gleason


Pattern (PGP) and Highest Gleason Pattern


(HGP) OR < 1.0 (Increased expression is


negatively associated with higher risk of


upgrading/upstaging (good prognosis))










PGP
HGP











Gene
OR
p-value
OR
p-value





ABCC3
 .
   .
0.70
  0.0216


ABCC8
0.66
  0.0121
 .
   .


ABCG2
0.67
  0.0208
0.61
  0.0071


ACE
 .
   .
0.73
  0.0442


ACOX2
0.46
  0.0000
0.49
  0.0001


ADH5
0.69
  0.0284
0.59
  0.0047


AIG1
 .
   .
0.60
  0.0045


AKR1C1
 .
   .
0.66
  0.0095


ALDH1A2
0.36
<0.0001
0.36
<0.0001


ALKBH3
0.70
  0.0281
0.61
  0.0056


ANPEP
 .
   .
0.68
  0.0109


ANXA2
0.73
  0.0411
0.66
  0.0080


APC
 .
   .
0.68
  0.0223


ATXN1
 .
   .
0.70
  0.0188


AXIN2
0.60
  0.0072
0.68
  0.0204


AZGP1
0.66
  0.0089
0.57
  0.0028


BCL2
.
   .
0.71
  0.0182


BIN1
0.55
  0.0005
 .
   .


BTRC
0.69
  0.0397
0.70
  0.0251


C7
0.53
  0.0002
0.51
<0.0001


CADM1
0.57
  0.0012
0.60
  0.0032


CASP1
0.64
  0.0035
0.72
  0.0210


CAV1
0.64
  0.0097
0.59
  0.0032


CAV2
 .
   .
0.58
  0.0107


CD164
 .
   .
0.69
  0.0260


CD82
0.67
  0.0157
0.69
  0.0167


CDH1
0.61
  0.0012
0.70
  0.0210


CDK14
0.70
  0.0354
 .
   .


CDK3
 .
   .
0.72
  0.0267


CDKN1C
0.61
  0.0036
0.56
  0.0003


CHN1
0.71
  0.0214
 .
   .


COL6A1
0.62
  0.0125
0.60
  0.0050


COL6A3
0.65
  0.0080
0.68
  0.0181


CSRP1
0.43
  0.0001
0.40
  0.0002


CTSB
0.66
  0.0042
0.67
  0.0051


CTSD
0.64
  0.0355
 .
   .


CTSK
0.69
  0.0171
 .
   .


CTSL1
0.72
  0.0402
 .
   .


CUL1
0.61
  0.0024
0.70
  0.0120


CXCL12
0.69
  0.0287
0.63
  0.0053


CYP3A5
0.68
  0.0099
0.62
  0.0026


DDR2
0.68
  0.0324
0.62
  0.0050


DES
0.54
  0.0013
0.46
  0.0002


DHX9
0.67
  0.0164
 .
   .


DLGAP1
 .
   .
0.66
  0.0086


DPP4
0.69
  0.0438
0.69
  0.0132


DPT
0.59
  0.0034
0.51
  0.0005


DUSP1
 .
   .
0.67
  0.0214


EDN1
 .
   .
0.66
  0.0073


EDNRA
0.66
  0.0148
0.54
  0.0005


EIF2C2
 .
   .
0.65
  0.0087


ELK4
0.55
  0.0003
0.58
  0.0013


ENPP2
0.65
  0.0128
0.59
  0.0007


EPHA3
0.71
  0.0397
0.73
  0.0455


EPHB2
0.60
  0.0014
 .
   .


EPHB4
0.73
  0.0418
 .
   .


EPHX3
 .
   .
0.71
  0.0419


ERCC1
0.71
  0.0325
 .
   .


FAM107A
0.56
  0.0008
0.55
  0.0011


FAM13C
0.68
  0.0276
0.55
  0.0001


FAS
0.72
  0.0404
 .
   .


FBN1
0.72
  0.0395
 .
   .


FBXW7
0.69
  0.0417
 .
   .


FGF10
0.59
  0.0024
0.51
  0.0001


FGF7
0.51
  0.0002
0.56
  0.0007


FGFR2
0.54
  0.0004
0.47
<0.0001


FLNA
0.58
  0.0036
0.50
  0.0002


FLNC
0.45
  0.0001
0.40
<0.0001


FLT4
0.61
  0.0045
 .
   .


FOXO1
0.55
  0.0005
0.53
  0.0005


FOXP3
0.71
  0.0275
0.72
  0.0354


GHR
0.59
  0.0074
0.53
  0.0001


GNRH1
0.72
  0.0386
 .
   .


GPM6B
0.59
  0.0024
0.52
  0.0002


GSN
0.65
  0.0107
0.65
  0.0098


GSTM1
0.44
<0.0001
0.43
<0.0001


GSTM2
0.42
<0.0001
0.39
<0.0001


HLF
0.46
<0.0001
0.47
  0.0001


HPS1
0.64
  0.0069
0.69
  0.0134


HSPA5
0.68
  0.0113
 .
   .


HSPB2
0.61
  0.0061
0.55
  0.0004


HSPG2
0.70
  0.0359
 .
   .


ID3
 .
   .
0.70
  0.0245


IGF1
0.45
<0.0001
0.50
  0.0005


IGF2
0.67
  0.0200
0.68
  0.0152


IGFBP2
0.59
  0.0017
0.69
  0.0250


IGFBP6
0.49
<0.0001
0.64
  0.0092


IL6ST
0.56
  0.0009
0.60
  0.0012


ILK
0.51
  0.0010
0.49
  0.0004


ITGA1
0.58
  0.0020
0.58
  0.0016


ITGA3
0.71
  0.0286
0.70
  0.0221


ITGA5
 .
   .
0.69
  0.0183


ITGA7
0.56
  0.0035
0.42
<0.0001


ITGB1
0.63
  0.0095
0.68
  0.0267


ITGB3
0.62
  0.0043
0.62
  0.0040


ITPR1
0.62
  0.0032
 .
   .


JUN
0.73
  0.0490
0.68
  0.0152


KIT
0.55
  0.0003
0.57
  0.0005


KLC1
 .
   .
0.70
  0.0248


KLK1
 .
   .
0.60
  0.0059


KRT15
0.58
  0.0009
0.45
<0.0001


KRT5
0.70
  0.0262
0.59
  0.0008


LAMA4
0.56
  0.0359
0.68
  0.0498


LAMB3
 .
   .
0.60
  0.0017


LGALS3
0.58
  0.0007
0.56
  0.0012


LRP1
0.69
  0.0176
 .
   .


MAP3K7
0.70
  0.0233
0.73
  0.0392


MCM3
0.72
  0.0320
 .
   .


MMP2
0.66
  0.0045
0.60
  0.0009


MMP7
0.61
  0.0015
0.65
  0.0032


MMP9
0.64
  0.0057
0.72
  0.0399


MPPED2
0.72
  0.0392
0.63
  0.0042


MTA1
 .
   .
0.68
  0.0095


MTSS1
0.58
  0.0007
0.71
  0.0442


MVP
0.57
  0.0003
0.70
  0.0152


MYBPC1
 .
   .
0.70
  0.0359


NCAM1
0.63
  0.0104
0.64
  0.0080


NCAPD3
0.67
  0.0145
0.64
  0.0128


NEXN
0.54
  0.0004
0.55
  0.0003


NFAT5
0.72
  0.0320
0.70
  0.0177


NUDT6
0.66
  0.0102
 .
   .


OLFML3
0.56
  0.0035
0.51
  0.0011


OMD
0.61
  0.0011
0.73
  0.0357


PAGE4
0.42
<0.0001
0.36
<0.0001


PAK6
0.72
  0.0335
 .
   .


PCDHGB7
0.70
  0.0262
0.55
  0.0004


PGF
0.72
  0.0358
0.71
  0.0270


PLP2
0.66
  0.0088
0.63
  0.0041


PPAP2B
0.44
<0.0001
0.50
  0.0001


PPP1R12A
0.45
  0.0001
0.40
<0.0001


PRIMA1
 .
   .
0.63
  0.0102


PRKAR2B
0.71
  0.0226
 .
   .


PRKCA
0.34
<0.0001
0.42
<0.0001


PRKCB
0.66
  0.0120
0.49
<0.0001


PROM1
0.61
  0.0030
 .
   .


PTEN
0.59
  0.0008
0.55
  0.0001


PTGER3
0.67
  0.0293
 .
   .


PTH1R
0.69
  0.0259
0.71
  0.0327


PTK2
0.75
  0.0461
 .
   .


PTK2B
0.70
  0.0244
0.74
  0.0388


PYCARD
0.73
  0.0339
0.67
  0.0100


RAD9A
0.64
  0.0124
 .
   .


RARB
0.67
  0.0088
0.65
  0.0116


RGS10
0.70
  0.0219
 .
   .


RHOB
 .
   .
0.72
  0.0475


RND3
 .
   .
0.67
  0.0231


SDHC
0.72
  0.0443
 .
   .


SEC23A
0.66
  0.0101
0.53
  0.0003


SEMA3A
0.51
  0.0001
0.69
  0.0222


SH3RF2
0.55
  0.0002
0.54
  0.0002


SLC22A3
0.48
  0.0001
0.50
  0.0058


SMAD4
0.49
  0.0001
0.50
  0.0003


SMARCC2
0.59
  0.0028
0.65
  0.0052


SMO
0.60
  0.0048
0.52
<0.0001


SORBS1
0.56
  0.0024
0.48
  0.0002


SPARCL1
0.43
  0.0001
0.50
  0.0001


SRD5A2
0.26
<0.0001
0.31
<0.0001


ST5
0.63
  0.0103
0.52
  0.0006


STAT5A
0.60
  0.0015
0.61
  0.0037


STAT5B
0.54
  0.0005
0.57
  0.0008


SUMO1
0.65
  0.0066
0.66
  0.0320


SVIL
0.52
  0.0067
0.46
  0.0003


TGFB1I1
0.44
  0.0001
0.43
  0.0000


TGFB2
0.55
  0.0007
0.58
  0.0016


TGFB3
0.57
  0.0010
0.53
  0.0005


TIMP1
0.72
  0.0224
 .
   .


TIMP2
0.68
  0.0198
0.69
  0.0206


TIMP3
0.67
  0.0105
0.64
  0.0065


TMPRSS2
 .
   .
0.72
  0.0366


TNFRSF10A
0.71
  0.0181
 .
   .


TNFSF10
0.71
  0.0284
 .
   .


TOP2B
0.73
  0.0432
 .
   .


TP63
0.62
  0.0014
0.50
<0.0001


TPM1
0.54
  0.0007
0.52
  0.0002


TPM2
0.41
<0.0001
0.40
<0.0001


TPP2
0.65
  0.0122
 .
   .


TRA2A
0.72
  0.0318
 .
   .


TRAF3IP2
0.62
  0.0064
0.59
  0.0053


TRO
0.57
  0.0003
0.51
  0.0001


VCL
0.52
  0.0005
0.52
  0.0004


VIM
0.65
  0.0072
0.65
  0.0045


WDR19
0.66
  0.0097
 .
   .


WFDC1
0.58
  0.0023
0.60
  0.0026


ZFHX3
0.69
  0.0144
0.62
  0.0046


ZNF827
0.62
  0.0030
0.53
  0.0001









Example 3: Identification of MicroRNAs Associated with Clinical Recurrence and Death Due to Prostate Cancer

MicroRNAs function by binding to portions of messenger RNA (mRNA) and changing how frequently the mRNA is translated into protein. They can also influence the turnover of mRNA and thus how long the mRNA remains intact in the cell. Since microRNAs function primarily as an adjunct to mRNA, this study evaluated the joint prognostic value of microRNA expression and gene (mRNA) expression. Since the expression of certain microRNAs may be a surrogate for expression of genes that are not in the assessed panel, we also evaluated the prognostic value of microRNA expression by itself.


Patients and Samples


Samples from the 127 patients with clinical recurrence and 374 patients without clinical recurrence after radical prostatectomy described in Example 2 were used in this study. The final analysis set comprised 416 samples from patients in which both gene expression and microRNA expression were successfully assayed. Of these, 106 patients exhibited clinical recurrence and 310 did not have clinical recurrence. Tissue samples were taken from each prostate sample representing (1) the primary Gleason pattern in the sample, and (2) the highest Gleason pattern in the sample. In addition, a sample of histologically normal-appearing tissue adjacent to the tumor (NAT) was taken. The number of patients in the analysis set for each tissue type and the number of them who experienced clinical recurrence or death due to prostate cancer are shown in Table 14.









TABLE 14







Number of Patients and Events in Analysis Set














Clinical
Deaths Due to




Patients
Recurrences
Prostate Cancer
















Primary Gleason
416
106
36



Pattern Tumor Tissue






Highest Gleason
405
102
36



Pattern Tumor Tissue






Normal Adjacent
364
 81
29



Tissue










Assay Method


Expression of 76 test microRNAs and 5 reference microRNAs were determined from RNA extracted from fixed paraffin-embedded (FPE) tissue. MicroRNA expression in all three tissue type was quantified by reverse transcriptase polymerase chain reaction (RT-PCR) using the crossing point (Cp) obtained from the Taqman® MicroRNA Assay kit (Applied Biosystems, Inc., Carlsbad, Calif.).


Statistical Analysis


Using univariate proportional hazards regression (Cox DR, Journal of the Royal Statistical Society, Series B 34:187-220, 1972), applying the sampling weights from the cohort sampling design, and using variance estimation based on the Lin and Wei method (Lin and Wei, Journal of the American Statistical Association 84:1074-1078, 1989), microRNA expression, normalized by the average expression for the 5 reference microRNAs hsa-miR-106a, hsa-miR-146b-5p, hsa-miR-191, hsa-miR-19b, and hsa-miR-92a, and reference-normalized gene expression of the 733 genes (including the reference genes) discussed above, were assessed for association with clinical recurrence and death due to prostate cancer. Standardized hazard ratios (the proportional change in the hazard associated with a change of one standard deviation in the covariate value) were calculated.


This analysis included the following classes of predictors:


1. MicroRNAs alone


2. MicroRNA-gene pairs Tier 1


3. MicroRNA-gene pairs Tier 2


4. MicroRNA-gene pairs Tier 3


5. All other microRNA-gene pairs Tier 4


The four tiers were pre-determined based on the likelihood (Tier 1 representing the highest likelihood) that the gene-microRNA pair functionally interacted or that the microRNA was related to prostate cancer based on a review of the literature and existing microarray data sets.


False discovery rates (FDR) (Benjamini and Hochberg, Journal of the Royal Statistical Society, Series B 57:289-300, 1995) were assessed using Efron's separate class methodology (Efron, Annals of Applied Statistics 2:197-223, 2008). The false discovery rate is the expected proportion of the rejected null hypotheses that are rejected incorrectly (and thus are false discoveries). Efron's methodology allows separate FDR assessment (q-values) (Storey, Journal of the Royal Statistical Society, Series B 64:479-498, 2002) within each class while utilizing the data from all the classes to improve the accuracy of the calculation. In this analysis, the q-value for a microRNA or microRNA-gene pair can be interpreted as the empirical Bayes probability that the microRNA or microRNA-gene pair identified as being associated with clinical outcome is in fact a false discovery given the data. The separate class approach was applied to a true discovery rate degree of association (TDRDA) analysis (Crager, Statistics in Medicine 29:33-45, 2010) to determine sets of microRNAs or microRNA-gene pairs that have standardized hazard ratio for clinical recurrence or prostate cancer-specific death of at least a specified amount while controlling the FDR at 10%. For each microRNA or microRNA-gene pair, a maximum lower bound (MLB) standardized hazard ratio was computed, showing the highest lower bound for which the microRNA or microRNA-gene pair was included in a TDRDA set with 10% FDR. Also calculated was an estimate of the true standardized hazard ratio corrected for regression to the mean (RM) that occurs in subsequent studies when the best predictors are selected from a long list (Crager, 2010 above). The RM-corrected estimate of the standardized hazard ratio is a reasonable estimate of what could be expected if the selected microRNA or microRNA-gene pair were studied in a separate, subsequent study.


These analyses were repeated adjusting for clinical and pathology covariates available at the time of patient biopsy: biopsy Gleason score, baseline PSA level, and clinical T-stage (T1-T2A vs. T2B or T2C) to assess whether the microRNAs or microRNA-gene pairs have predictive value independent of these clinical and pathology covariates.


Results

The analysis identified 21 microRNAs assayed from primary Gleason pattern tumor tissue that were associated with clinical recurrence of prostate cancer after radical prostatectomy, allowing a false discovery rate of 10% (Table 15). Results were similar for microRNAs assessed from highest Gleason pattern tumor tissue (Table 16), suggesting that the association of microRNA expression with clinical recurrence does not change markedly depending on the location within a tumor tissue sample. No microRNA assayed from normal adjacent tissue was associated with the risk of clinical recurrence at a false discovery rate of 10%. The sequences of the microRNAs listed in Tables 15-21 are shown in Table B.









TABLE 15







MicroRNAs Associated with Clinical Recurrence of Prostate Cancer


Primary Gleason Pattern Tumor Tissue















Absolute Standardized Hazard Ratio

















Direction
Uncor-
95%
Max. Lower
RM-




q-valuea
of Asso-
rected
Confidence
Bound
Corrected


MicroRNA
p-value
(FDR)
ciationb
Estimate
Interval
@10% FDR
Estimatec

















hsa-miR-93
<0.0001
0.0%
(+)
1.79
(1.38, 2.32)
1.19
1.51


hsa-miR-106b
<0.0001
0.1%
(+)
1.80
(1.38,2.34)
1.19
1.51


hsa-miR-30e-5p
<0.0001
0.1%
(−)
1.63
(1.30, 2.04)
1.18
1.46


hsa-miR-21
<0.0001
0.1%
(+)
1.66
(1.31,2.09)
1.18
1.46


hsa-miR-133a
<0.0001
0.1%
(−)
1.72
(1.33, 2.21)
1.18
1.48


hsa-miR-449a
<0.0001
0.1%
(+)
1.56
(1.26, 1.92)
1.17
1.42


hsa-miR-30a
0.0001
0.1%
(−)
1.56
(1.25, 1.94)
1.16
1.41


hsa-miR-182
0.0001
0.2%
(+)
1.74
(1.31, 2.31)
1.17
1.45


hsa-miR-27a
0.0002
0.2%
(+)
1.65
(1.27, 2.14)
1.16
1.43


hsa-miR-222
0.0006
0.5%
(−)
1.47
(1.18, 1.84)
1.12
1.35


hsa-miR-103
0.0036
2.1%
(+)
1.77
(1.21, 2.61)
1.12
1.36


hsa-miR-1
0.0037
2.2%
(−)
1.32
(1.10, 1.60)
1.07
1.26


hsa-miR-145
0.0053
2.9%
(−)
1.34
(1.09, 1.65)
1.07
1.27


hsa-miR-141
0.0060
3.2%
(+)
1.43
(1.11, 1.84)
1.07
1.29


hsa-miR-92a
0.0104
4.8%
(+)
1.32
(1.07, 1.64)
1.05
1.25


hsa-miR-22
0.0204
7.7%
(+)
1.31
(1.03, 1.64)
1.03
1.23


hsa-miR-29b
0.0212
7.9%
(+)
1.36
(1.03, 1.76)
1.03
1.24


hsa-miR-210
0.0223
8.2%
(+)
1.33
(1.03, 1.70)
1.00
1.23


hsa-miR-486-5p
0.0267
9.4%
(−)
1.25
(1.00, 1.53)
1.00
1.20


hsa-miR-19b
0.0280
9.7%
(−)
1.24
(1.00, 1.50)
1.00
1.19


hsa-miR-205
0.0289
10.0%
(−)
1.25
(1.00, 1.53)
1.00
1.20






aThe q-value is the empirical Bayes probability that the microRNA's association with clinical recurrence is a false discovery, given the data.




bDirection of association indicates where higher microRNA expression is associated with higher (+) or lower (−) risk of clinical recurrence.




cRM: regression to the mean.














TABLE 16







MicroRNAs Associated with Clinical Recurrence of Prostate Cancer


Highest Gleason Pattern Tumor Tissue















Absolute Standardized Hazard Ratio

















Direction
Uncor-
95%
Max. Lower
RM-




q-valuea
of Asso-
rected
Confidence
Bound
Corrected


MicroRNA
p-value
(FDR)
ciationb
Estimate
Interval
@10% FDR
Estimatec

















hsa-miR-93
<0.0001
0.0%
(+)
1.91
(1.48, 2.47)
1.24
1.59


hsa-miR-449a
<0.0001
0.0%
(+)
1.75
(1.40, 2.18)
1.23
1.54


hsa-miR-205
<0.0001
0.0%
(−)
1.53
(1.29, 1.81)
1.20
1.43


hsa-miR-19b
<0.0001
0.0%
(−)
1.37
(1.19, 1.57)
1.15
1.32


hsa-miR-106b
<0.0001
0.0%
(+)
1.84
(1.39, 2.42)
1.22
1.51


hsa-miR-21
<0.0001
0.0%
(+)
1.68
(1.32, 2.15)
1.19
1.46


hsa-miR-30a
0.0005
0.4%
(−)
1.44
(1.17, 1.76)
1.13
1.33


hsa-miR-30e-5p
0.0010
0.6%
(−)
1.37
(1.14, 1.66)
1.11
1.30


hsa-miR-133a
0.0015
0.8%
(−)
1.57
(1.19, 2.07)
1.13
1.36


hsa-miR-1
0.0016
0.8%
(−)
1.42
(1.14, 1.77)
1.11
1.31


hsa-miR-103
0.0021
1.1%
(+)
1.69
(1.21, 2.37)
1.13
1.37


hsa-miR-210
0.0024
1.2%
(+)
1.43
(1.13, 1.79)
1.11
1.31


hsa-miR-182
0.0040
1.7%
(+)
1.48
(1.13, 1.93)
1.11
1.31


hsa-miR-27a
0.0055
2.1%
(+)
1.46
(1.12, 1.91)
1.09
1.30


hsa-miR-222
0.0093
3.2%
(−)
1.38
(1.08, 1.77)
1.08
1.27


hsa-miR-331
0.0126
3.9%
(+)
1.38
(1.07, 1.77)
1.07
1.26


hsa-miR-191*
0.0143
4.3%
(+)
1.38
(1.06, 1.78)
1.07
1.26


hsa-miR-425
0.0151
4.5%
(+)
1.40
(1.06, 1.83)
1.07
1.26


hsa-miR-31
0.0176
5.1%
(−)
1.29
(1.04, 1.60)
1.05
1.22


hsa-miR-92a
0.0202
5.6%
(+)
1.31
(1.03, 1.65)
1.05
1.23


hsa-miR-155
0.0302
7.6%
(−)
1.32
(1.00, 1.69)
1.03
1.22


hsa-miR-22
0.0437
9.9%
(+)
1.30
(1.00, 1.67)
1.00
1.21






aThe q-value is the empirical Bayes probability that the microRNA's association with death due to prostate cancer is a false discovery, given the data.




bDirection of association indicates where higher microRNA expression is associated with higher (+) or lower (−) risk of clinical recurrence.




cRM: regression to the mean.







Table 17 shows microRNAs assayed from primary Gleason pattern tissue that were identified as being associated with the risk of prostate-cancer-specific death, with a false discovery rate of 10%. Table 18 shows the corresponding analysis for microRNAs assayed from highest Gleason pattern tissue. No microRNA assayed from normal adjacent tissue was associated with the risk of prostate-cancer-specific death at a false discovery rate of 10%.









TABLE 17







MicroRNAs Associated with Death Due to Prostate Cancer


Primary Gleason Pattern Tumor Tissue















Absolute Standardized Hazard Ratio




















Max.









Lower






Direction
Uncor-
95%
Bound
RM-




q-valuea
of Asso-
rected
Confidence
@10%
Corrected


MicroRNA
p-value
(FDR)
ciationb
Estimate
Interval
FDR
Estimatec





hsa-miR-30e-5p
0.0001
0.6%
(−)
1.88
(1.37, 2.58)
1.15
1.46


hsa-miR-30a
0.0001
0.7%
(−)
1.78
(1.33, 2.40)
1.14
1.44


hsa-miR-133a
0.0005
1.2%
(−)
1.85
(1.31, 2.62)
1.13
1.41


hsa-miR-222
0.0006
1.4%
(−)
1.65
(1.24, 2.20)
1.12
1.38


hsa-miR-106b
0.0024
2.7%
(+)
1.85
(1.24, 2.75)
1.11
1.35


hsa-miR-1
0.0028
3.0%
(−)
1.43
(1.13, 1.81)
1.08
1.30


hsa-miR-21
0.0034
3.3%
(+)
1.63
(1.17, 2.25)
1.09
1.33


hsa-miR-93
0.0044
3.9%
(+)
1.87
(1.21, 2.87)
1.09
1.32


hsa-miR-26a
0.0072
5.3%
(−)
1.47
(1.11, 1.94)
1.07
1.29


hsa-miR-152
0.0090
6.0%
(−)
1.46
(1.10, 1.95)
1.06
1.28


hsa-miR-331
0.0105
6.5%
(+)
1.46
(1.09, 1.96)
1.05
1.27


hsa-miR-150
0.0159
8.3%
(+)
1.51
(1.07, 2.10)
1.03
1.27


hsa-miR-27b
0.0160
8.3%
(+)
1.97
(1.12, 3.42)
1.05
1.25






aThe q-value is the empirical Bayes probability that the microRNA's association with death due to prostate cancer endpoint is a false discovery, given the data.




bDirection of association indicates where higher microRNA expression is associated with higher (+) or lower (−) risk of death due to prostate cancer.




cRM: regression to the mean.














TABLE 18







MicroRNAs Associated with Death Due to Prostate Cancer


Highest Gleason Pattern Tumor Tissue















Absolute Standardized Hazard Ratio




















Max.









Lower






Direction
Uncor-
95%
Bound
RM-




q-valuea
of Asso-
rected
Confidence
@10%
Corrected


MicroRNA
p-value
(FDR)
ciationb
Estimate
Interval
FDR
Estimatec





hsa-miR-27b
0.0016
6.1%
(+)
2.66
(1.45, 4.88)
1.07
1.32


hsa-miR-21
0.0020
6.4%
(+)
1.66
(1.21, 2.30)
1.05
1.34


hsa-miR-10a
0.0024
6.7%
(+)
1.78
(1.23, 2.59)
1.05
1.34


hsa-miR-93
0.0024
6.7%
(+)
1.83
(1.24, 2.71)
1.05
1.34


hsa-miR-106b
0.0028
6.8%
(+)
1.79
(1.22, 2.63)
1.05
1.33


hsa-miR-150
0.0035
7.1%
(+)
1.61
(1.17, 2.22)
1.05
1.32


hsa-miR-1
0.0104
9.0%
(−)
1.52
(1.10, 2.09)
1.00
1.28






aThe q-value is the empirical Bayes probability that the microRNA's association with clinical endpoint is a false discovery, given the data.




bDirection of association indicates where higher microRNA expression is associated with higher (+) or lower (−) risk of death due to prostate cancer.




cRM: regression to the mean.







Table 19 and Table 20 shows the microRNAs that can be identified as being associated with the risk of clinical recurrence while adjusting for the clinical and pathology covariates of biopsy Gleason score, baseline PSA level, and clinical T-stage. The distributions of these covariates are shown in FIG. 1. Fifteen (15) of the microRNAs identified in Table 15 are also present in Table 19, indicating that these microRNAs have predictive value for clinical recurrence that is independent of the Gleason score, baseline PSA, and clinical T-stage.


Two microRNAs assayed from primary Gleason pattern tumor tissue were found that had predictive value for death due to prostate cancer independent of Gleason score, baseline PSA, and clinical T-stage (Table 21).









TABLE 19







MicroRNAs Associated with Clinical Recurrence of Prostate Cancer


Adjusting for Biopsy Gleason Score, Baseline PSA Level, and Clinical


T-Stage Primary Gleason Pattern Tumor Tissue















Absolute Standardized Hazard Ratio




















Max.









Lower






Direction
Uncor-
95%
Bound
RM-




q-valuea
of Asso-
rected
Confidence
@10%
Corrected


MicroRNA
p-value
(FDR)
ciationb
Estimate
Interval
FDR
Estimatec

















hsa-miR-30e-5p
<0.0001
0.0%
(−)
1.80
(1.42, 2.27)
1.23
1.53


hsa-miR-30a
<0.0001
0.0%
(−)
1.75
(1.40, 2.19)
1.22
1.51


hsa-miR-93
<0.0001
0.1%
(+)
1.70
(1.32, 2.20)
1.19
1.44


hsa-miR-449a
0.0001
0.1%
(+)
1.54
(1.25, 1.91)
1.17
1.39


hsa-miR-133a
0.0001
0.1%
(−)
1.58
(1.25, 2.00)
1.17
1.39


hsa-miR-27a
0.0002
0.1%
(+)
1.66
(1.28, 2.16)
1.17
1.41


hsa-miR-21
0.0003
0.2%
(+)
1.58
(1.23, 2.02)
1.16
1.38


hsa-miR-182
0.0005
0.3%
(+)
1.56
(1.22, 1.99)
1.15
1.37


hsa-miR-106b
0.0008
0.5%
(+)
1.57
(1.21, 2.05)
1.15
1.36


hsa-miR-222
0.0028
1.1%
(−)
1.39
(1.12, 1.73)
1.11
1.28


hsa-miR-103
0.0048
1.7%
(+)
1.69
(1.17, 2.43)
1.13
1.32


hsa-miR-486-5p
0.0059
2.0%
(−)
1.34
(1.09, 1.65)
1.09
1.25


hsa-miR-1
0.0083
2.7%
(−)
1.29
(1.07, 1.57)
1.07
1.23


hsa-miR-141
0.0088
2.8%
(+)
1.43
(1.09, 1.87)
1.09
1.27


hsa-miR-200c
0.0116
3.4%
(+)
1.39
(1.07, 1.79)
1.07
1.25


hsa-miR-145
0.0201
5.1%
(−)
1.27
(1.03, 1.55)
1.05
1.20


hsa-miR-206
0.0329
7.2%
(−)
1.40
(1.00, 1.91)
1.05
1.23


hsa-miR-29b
0.0476
9.4%
(+)
1.30
(1.00, 1.69)
1.00
1.20






aThe q-value is the empirical Bayes probability that the microRNA's association with clinical recurrence is a false discovery, given the data.




bDirection of association indicates where higher microRNA expression is associated with higher (+) or lower (−) risk of clinical recurrence.




cRM: regression to the mean.














TABLE 20







MicroRNAs Associated with Clinical Recurrence of Prostate Cancer


Adjusting for Biopsy Gleason Score, Baseline PSA Level, and Clinical T-Stage


Highest Gleason Pattern Tumor Tissue















Absolute Standardized Hazard Ratio




















Max.









Lower






Direction
Uncor-
95%
Bound
RM-




q-valuea
of Asso-
rected
Confidence
@10%
Corrected


MicroRNA
p-value
(FDR)
ciationb
Estimate
Interval
FDR
Estimatec

















hsa-miR-30a
<0.0001
0.0%
(−)
1.62
(1.32, 1.99)
1.20
1.43


hsa-miR-30e-5p
<0.0001
0.0%
(−)
1.53
(1.27, 1.85)
1.19
1.39


hsa-miR-93
<0.0001
0.0%
(+)
1.76
(1.37, 2.26)
1.20
1.45


hsa-miR-205
<0.0001
0.0%
(−)
1.47
(1.23, 1.74)
1.18
1.36


hsa-miR-449a
0.0001
0.1%
(+)
1.62
(1.27, 2.07)
1.18
1.38


hsa-miR-106b
0.0003
0.2%
(+)
1.65
(1.26, 2.16)
1.17
1.36


hsa-miR-133a
0.0005
0.2%
(−)
1.51
(1.20, 1.90)
1.16
1.33


hsa-miR-1
0.0007
0.3%
(−)
1.38
(1.15, 1.67)
1.13
1.28


hsa-miR-210
0.0045
1.2%
(+)
1.35
(1.10, 1.67)
1.11
1.25


hsa-miR-182
0.0052
1.3%
(+)
1.40
(1.10, 1.77)
1.11
1.26


hsa-miR-425
0.0066
1.6%
(+)
1.48
(1.12, 1.96)
1.12
1.26


hsa-miR-155
0.0073
1.8%
(−)
1.36
(1.09, 1.70)
1.10
1.24


hsa-miR-21
0.0091
2.1%
(+)
1.42
(1.09, 1.84)
1.10
1.25


hsa-miR-222
0.0125
2.7%
(−)
1.34
(1.06, 1.69)
1.09
1.23


hsa-miR-27a
0.0132
2.8%
(+)
1.40
(1.07, 1.84)
1.09
1.23


hsa-miR-191*
0.0150
3.0%
(+)
1.37
(1.06, 1.76)
1.09
1.23


hsa-miR-103
0.0180
3.4%
(+)
1.45
(1.06, 1.98)
1.09
1.23


hsa-miR-31
0.0252
4.3%
(−)
1.27
(1.00, 1.57)
1.07
1.19


hsa-miR-19b
0.0266
4.5%
(−)
1.29
(1.00, 1.63)
1.07
1.20


hsa-miR-99a
0.0310
5.0%
(−)
1.26
(1.00, 1.56)
1.06
1.18


hsa-miR-92a
0.0348
5.4%
(+)
1.31
(1.00, 1.69)
1.06
1.19


hsa-miR-146b-5p
0.0386
5.8%
(−)
1.29
(1.00, 1.65)
1.06
1.19


hsa-miR-145
0.0787
9.7%
(−)
1.23
(1.00, 1.55)
1.00
1.15






aThe q-value is the empirical Bayes probability that the microRNA's association with clinical clinical recurrence is a false discovery, given the data.




bDirection of association indicates where higher microRNA expression is associated with higher (+) or lower (−) risk of clinical recurrence.




cRM: regression to the mean.














TABLE 21







MicroRNAs Associated with Death Due to Prostate Cancer


Adjusting for Biopsy Gleason Score, Baseline PSA Level, and Clinical


T-Stage Primary Gleason Pattern Tumor Tissue















Absolute Standardized Hazard Ratio




















Max.









Lower






Direction
Uncor-
95%
Bound
RM-




q-valuea
of Asso-
rected
Confidence
@10%
Corrected


MicroRNA
p-value
(FDR)
ciationb
Estimate
Interval
FDR
Estimatec





hsa-miR-30e-5p
0.0001
2.9%
(−)
1.97
(1.40, 2.78)
1.09
1.39


hsa-miR-30a
0.0002
3.3%
(−)
1.90
(1.36, 2.65)
1.08
1.38






aThe q-value is the empirical Bayes probability that the microRNA's association with clinical recurrence is a false discovery, given the data.




bDirection of association indicates where higher microRNA expression is associated with higher (+) or lower (−) risk of clinical recurrence.




cRM: regression to the mean.







Accordingly, the normalized expression levels of hsa-miR-93; hsa-miR-106b; hsa-miR-21; hsa-miR-449a; hsa-miR-182; hsa-miR-27a; hsa-miR-103; hsa-miR-141; hsa-miR-92a; hsa-miR-22; hsa-miR-29b; hsa-miR-210; hsa-miR-331; hsa-miR-191; hsa-miR-425; and hsa-miR-200c are positively associated with an increased risk of recurrence; and hsa-miR-30e-5p; hsa-miR-133a; hsa-miR-30a; hsa-miR-222; hsa-miR-1; hsa-miR-145; hsa-miR-486-5p; hsa-miR-19b; hsa-miR-205; hsa-miR-31; hsa-miR-155; hsa-miR-206; hsa-miR-99a; and hsa-miR-146b-5p are negatively associated with an increased risk of recurrence.


Furthermore, the normalized expression levels of hsa-miR-106b; hsa-miR-21; hsa-miR-93; hsa-miR-331; hsa-miR-150; hsa-miR-27b; and hsa-miR-10a are positively associated with an increased risk of prostate cancer specific death; and the normalized expression levels of hsa-miR-30e-5p; hsa-miR-30a; hsa-miR-133a; hsa-miR-222; hsa-miR-1; hsa-miR-26a; and hsa-miR-152 are negatively associated with an increased risk of prostate cancer specific death.


Table 22 shows the number of microRNA-gene pairs that were grouped in each tier (Tiers 1-4) and the number and percentage of those that were predictive of clinical recurrence at a false discovery rate of 10%.













TABLE 22









Number of Pairs




Total
Predictive of Clinical




Number of
Recurrence at False




MicroRNA-
Discovery Rate 10%



Tier
Gene Pairs
(%)









Tier 1
   80
   46 (57.5%)



Tier 2
  719
  591 (82.2%)



Tier 3
 3,850
 2,792 (72.5%)



Tier 4
54,724
38,264 (69.9%)






















TABLE A









SEQ

SEQ



Official
Accession
ID

ID



Symbol:
Number:
NO
Forward Primer Sequence:
NO
Reverse Primer Sequence:





AAMP
NM_001087
1
GTGTGGCAGGTGGACACTAA
2
CTCCATCCACTCCAGGTCTC





ABCA5
NM_172232
5
GGTATGGATCCCAAAGCCA
6
CAGCCCGCTTTCTGTTTTTA





ABCB1
NM_000927
9
AAACACCACTGGAGCATTGA
10
CAAGCCTGGAACCTATAGCC





ABCC1
NM_004996
13
TCATGGTGCCCGTCAATG
14
CGATTGTCTTTGCTCTTCATGTG





ABCC3
NM_003786
17
TCATCCTGGCGATCTACTTCCT
18
CCGTTGAGTGGAATCAGCAA





ABCC4
NM_005845
21
AGCGCCTGGAATCTACAACT
22
AGAGCCCCTGGAGAGAAGAT





ABCC8
NM_000352
25
CGTCTGTCACTGTGGAGTGG
26
TGATCCGGTTTAGCAGGC





ABCG2
NM_004827
29
GGTCTCAACGCCATCCTG
30
CTTGGATCTTTCCTTGCAGC





ABHD2
NM_007011
33
GTAGTGGGTCTGCATGGATGT
34
TGAGGGTTGGCACTCAGG





ACE
NM_000789
37
CCGCTGTACGAGGATTTCA
38
CCGTGTCTGTGAAGCCGT





ACOX2
NM_003500
41
ATGGAGGTGCCCAGAACAC
42
ACTCCGGGTAACTGTGGATG





ACTR2
NM_005722
45
ATCCGCATTGAAGACCCA
46
ATCCGCTAGAACTGCACCAC





ADAM15
NM_003815
49
GGCGGGATGTGGTAACAG
50
ATTTCTGGGCCTCCGAGT





ADAMTS1
NM_006988
53
GGACAGGTGCAAGCTCATCTG
54
ATCTACAACCTTGGGCTGCAA





ADH5
NM_000671
57
ATGCTGTCATCATTGTCACG
58
CTGCTTCCTTTCCCTTTCC





AFAP1
NM_198595
61
GATGTCCATCCTTGAAACAGC
62
CAACCCTGATGCCTGGAG





AGTR1
NM_000685
65
AGCATTGATCGATACCTGGC
66
CTACAAGCATTGTGCGTCG





AGTR2
NM_000686
69
ACTGGCATAGGAAATGGTATCC
70
ATTGACTGGGTCTCTTTGCC





AIG1
NM_016108
73
CGACGGTTCTGCCCTTTAT
74
TGCTCCTGCTGGGATACTG





AKAP1
NM_003488
77
TGTGGTTGGAGATGAAGTGG
78
GTCTACCCACTGGGCAAGG





AKR1C1
BC040210
81
GTGTGTGAAGCTGAATGATGG
82
CTCTGCAGGCGCATAGGT





AKR1C3
NM_003739
85
GCTTTGCCTGATGTCTACCAGAA
86
GTCCAGTCACCGGCATAGAGA





AKT1
NM_005163
89
CGCTTCTATGGCGCTGAGAT
90
TCCCGGTACACCACGTTCTT





AKT2
NM_001626
93
TCCTGCCACCCTTCAAACC
94
GGCGGTAAATTCATCATCGAA





AKT3
NM_005465
97
TTGTCTCTGCCTTGGACTATCTACA
98
CCAGCATTAGATTCTCCAACTTGA





ALCAM
NM_001627
101
GAGGAATATGGAATCCAAGGG
102
GTGGCGGAGATCAAGAGG





ALDH18A1
NM_002860
105
GATGCAGCTGGAACCCAA
106
CTCCAGCTCAGTGGGGAA





ALDH1A2
NM_170696
109
CACGTCTGTCCCTCTCTGCT
110
GACCGTGGCTCAACTTTGTAT





ALKBH3
NM_139178
113
TCGCTTAGTCTGCACCTCAAC
114
TCTGAGCCCCAGTTTTTCC





ALOX12
NM_000697
117
AGTTCCTCAATGGTGCCAAC
118
AGCACTAGCCTGGAGGGC





ALOX5
NM_000698
121
GAGCTGCAGGACTTCGTGA
122
GAAGCCTGAGGACTTGCG





AMACR
NM_203382
125
GTCTCTGGGCTGTCAGCTTT
126
TGGGTATAAGATCCAGAACTTGC





AMPD3
NM_000480
129
TGGTTCATCCAGCACAAGG
130
CATAAATCCGGGGCACCT





ANGPT2
NM_001147
133
CCGTGAAAGCTGCTCTGTAA
134
TTGCAGTGGGAAGAACAGTC





ANLN
NM_018685
137
TGAAAGTCCAAAACCAGGAA
138
CAGAACCAAGGCTATCACCA





ANPEP
NM_001150
141
CCACCTTGGACCAAAGTAAAGC
142
TCTCAGCGTCACCTGGTAGGA





ANXA2
NM_004039
145
CAAGACACTAAGGGCGACTACCA
146
CGTGTCGGGCTTCAGTCAT





APC
NM_000038
149
GGACAGCAGGAATGTGTTTC
150
ACCCACTCGATTTGTTTCTG





APEX1
NM_001641
153
GATGAAGCCTTTCGCAAGTT
154
AGGTCTCCACACAGCACAAG





APOC1
NM_001645
157
CCAGCCTGATAAAGGTCCTG
158
CACTCTGAATCCTTGCTGGA





APOE
NM_000041
161
GCCTCAAGAGCTGGTTCG
162
CCTGCACCTTCTCCACCA





APRT
NM_000485
165
GAGGTCCTGGAGTGCGTG
166
AGGTGCCAGCTTCTCCCT





AQP2
NM_000486
169
GTGTGGGTGCCAGTCCTC
170
CCCTTCAGCCCTCTCAAAG





AR
NM_000044
173
CGACTTCACCGCACCTGAT
174
TGACACAAGTGGGACTGGGATA





ARF1
NM_001658
177
CAGTAGAGATCCCCGCAACT
178
ACAAGCACATGGCTATGGAA





ARHGAP29
NM_004815
181
CACGGTCTCGTGGTGAAGT
182
CAGTTGCTTGCCCAGGAC





ARHGDIB
NM_001175
185
TGGTCCCTAGAACAAGAGGC
186
TGATGGAGGATCAGAGGGAG





ASAP2
NM_003887
189
CGGCCCATCAGCTTCTAC
190
CTCTGGCCAAAGATACAGCG





ASPN
NM_017680
193
TGGACTAATCTGTGGGAGCA
194
AAACACCCTTCAACACAGTCC





ATM
NM_000051
197
TGCTTTCTACACATGTTCAGGG
198
GTTGTGGATCGGCTCGTT





ATP5E
NM_006886
201
CCGCTTTCGCTACAGCAT
202
TGGGAGTATCGGATGTAGCTG





ATP5J
NM_
205
GTCGACCGACTGAAACGG
206
CTCTACTTCCGGCCCTGG



001003703









ATXN1
NM_000332
209
GATCGACTCCAGCACCGTAG
210
GAACTGTATCACGGCCACG





AURKA
NM_003600
213
CATCTTCCAGGAGGACCACT
214
TCCGACCTTCAATCATTTCA





AURKB
NM_004217
217
AGCTGCAGAAGAGCTGCACAT
218
GCATCTGCCAACTCCTCCAT





AXIN2
NM_004655
221
GGCTATGTCTTTGCACCAGC
222
ATCCGTCAGCGCATCACT





AZGP1
NM_001185
225
GAGGCCAGCTAGGAAGCAA
226
CAGGAAGGGCAGCTACTGG





BAD
NM_032989
229
GGGTCAGGGGCCTCGAGAT
230
CTGCTCACTCGGCTCAAACTC





BAG5
NM_
233
ACTCCTGCAATGAACCCTGT
234
ACAAACAGCTCCCCACGA



001015049









BAK1
NM_001188
237
CCATTCCCACCATTCTACCT
238
GGGAACATAGACCCACCAAT





BAX
NM_004324
241
CCGCCGTGGACACAGACT
242
TTGCCGTCAGAAAACATGTCA





BBC3
NM_014417
245
CCTGGAGGGTCCTGTACAAT
246
CTAATTGGGCTCCATCTCG





BCL2
NM_000633
249
CAGATGGACCTAGTACCCACTGAGA
250
CCTATGATTTAAGGGCATTTTTCC





BDKRB1
NM_000710
253
GTGGCAGAAATCTACCTGGC
254
GAAGGGCAAGCCCAAGAC





BGN
NM_001711
257
GAGCTCCGCAAGGATGAC
258
CTTGTTGTTCACCAGGACGA





BIK
NM_001197
261
ATTCCTATGGCTCTGCAATTGTC
262
GGCAGGAGTGAATGGCTCTTC





BIN1
NM_004305
265
CCTGCAAAAGGGAACAAGAG
266
CGTGGTTGACTCTGATCTCG





BIRC5
NM_
269
TTCAGGTGGATGAGGAGACA
270
CACACAGCAGTGGCAAAAG



001012271









BMP6
NM_001718
273
GTGCAGACCTTGGTTCACCT
274
CTTAGTTGGCGCACAGCAC





BMPR1B
NM_001203
277
ACCACTTTGGCCATCCCT
278
GCGGTGTTTGTACCCAGTG





BRCA1
NM_007294
281
TCAGGGGGCTAGAAATCTGT
282
CCATTCCAGTTGATCTGTGG





BRCA2
NM_000059
285
AGTTCGTGCTTTGCAAGATG
286
AAGGTAAGCTGGGTCTGCTG





BTG1
NM_001731
289
GAGGTCCGAGCGATGTGA
290
AGTTATTTTCGAGACAGGAGGC





BTG3
NM_006806
293
CCATATCGCCCAATTCCA
294
CCAGTGATTCCGGTCACAA





BTRC
NM_033637
297
GTTGGGACACAGTTGGTCTG
298
TGAAGCAGTCAGTTGTGCTG





BUB1
NM_004336
301
CCGAGGTTAATCCAGCACGTA
302
AAGACATGGCGCTCTCAGTTC





C7
NM_000587
305
ATGTCTGAGTGTGAGGCGG
306
AGGCCTTATGCTGGTGACAG





CACNA1D
NM_000720
309
AGGACCCAGCTCCATGTG
310
CCTACATTCCGTGCCATTG





CADM1
NM_014333
313
CCACCACCATCCTTACCATC
314
GATCCACTGCCCTGATCG





CADPS
NM_003716
317
CAGCAAGGAGACTGTGCTGA
318
GGTCCTCTTCTCCACGGTAGAT





CASP3
NM_032991
325
TGAGCCTGAGCAGAGACATGA
326
CCTTCCTGCGTGGTCCAT





CASP7
NM_033338
329
GCAGCGCCGAGACTTTTA
330
AGTCTCTCTCCGTCGCTCC





CAV1
NM_001753
333
GTGGCTCAACATTGTGTTCC
334
CAATGGCCTCCATTTTACAG





CAV2
NM_198212
337
CTTCCCTGGGACGACTTG
338
CTCCTGGTCACCCTTCTGG





CCL2
NM_002982
341
CGCTCAGCCAGATGCAATC
342
GCACTGAGATCTTCCTATTGGTGAA





CCL5
NM_002985
345
AGGTTCTGAGCTCTGGCTTT
346
ATGCTGACTTCCTTCCTGGT





CCNB1
NM_031966
349
TTCAGGTTGTTGCAGGAGAC
350
CATCTTCTTGGGCACACAAT





CCND1
NM_001758
353
GCATGTTCGTGGCCTCTAAGA
354
CGGTGTAGATGCACAGCTTCTC





CCNE2
NM_057749
357
ATGCTGTGGCTCCTTCCTAACT
358
ACCCAAATTGTGATATACAAAAAGGTT





CCNH
NM_001239
361
GAGATCTTCGGTGGGGGTA
362
CTGCAGACGAGAACCCAAAC





CCR1
NM_001295
365
TCCAAGACCCAATGGGAA
366
TCGTAGGCTTTCGTGAGGA





CD164
NM_006016
369
CAACCTGTGCGAAAGTCTACC
370
ACACCCAAGACCAGGACAAT





CD1A
NM_001763
373
GGAGTGGAAGGAACTGGAAA
374
TCATGGGCGTATCTACGAAT





CD276
NM_
377
CCAAAGGATGCGATACACAG
378
GGATGACTTGGGAATCATGTC



001024736









CD44
NM_000610
381
GGCACCACTGCTTATGAAGG
382
GATGCTCATGGTGAATGAGG





CD68
NM_001251
385
TGGTTCCCAGCCCTGTGT
386
CTCCTCCACCCTGGGTTGT





CD82
NM_002231
389
GTGCAGGCTCAGGTGAAGTG
390
GACCTCAGGGCGATTCATGA





CDC20
NM_001255
393
TGGATTGGAGTTCTGGGAATG
394
GCTTGCACTCCACAGGTACACA





CDC25B
NM_021873
397
GCTGCAGGACCAGTGAGG
398
TAGGGCAGCTGGCTTCAG





CDC6
NM_001254
401
GCAACACTCCCCATTTACCTC
402
TGAGGGGGACCATTCTCTTT





CDH1
NM_004360
405
TGAGTGTCCCCCGGTATCTTC
406
CAGCCGCTTTCAGATTTTCAT





CDH10
NM_006727
409
TGTGGTGCAAGTCACAGCTAC
410
TGTAAATGACTCTGGCGCTG





CDH11
NM_001797
413
GTCGGCAGAAGCAGGACT
414
CTACTCATGGGCGGGATG





CDH19
NM_021153
417
AGTACCATAATGCGGGAACG
418
AGACTGCCTGTATAGGCTCCTG





CDH5
NM_001795
421
ACAGGAGACGTGTTCGCC
422
CAGCAGTGAGGTGGTACTCTGA





CDH7
NM_033646
425
GTTTGACATGGCTGCACTGA
426
AGTCACATCCCTCCGGGT





CDK14
NM_012395
429
GCAAGGTAAATGGGAAGTTGG
430
GATAGCTGTGAAAGGTGTCCCT





CDK2
NM_001798
433
AATGCTGCACTACGACCCTA
434
TTGGTCACATCCTGGAAGAA





CDK3
NM_001258
437
CCAGGAAGGGACTGGAAGA
438
GTTGCATGAGCAGGTCCC





CDK7
NM_001799
441
GTCTCGGGCAAAGCGTTAT
442
CTCTGGCCTTGTAAACGGTG





CDKN1A
NM_000389
445
TGGAGACTCTCAGGGTCGAAA
446
GGCGTTTGGAGTGGTAGAAATC





CDKN1C
NM_000076
449
CGGCGATCAAGAAGCTGT
450
CAGGCGCTGATCTCTTGC





CDKN2B
NM_004936
453
GACGCTGCAGAGCACCTT
454
GCGGGAATCTCTCCTCAGT





CDKN2C
NM_001262
457
GAGCACTGGGCAATCGTTAC
458
CAAAGGCGAACGGGAGTAG





CDKN3
NM_005192
461
TGGATCTCTACCAGCAATGTG
462
ATGTCAGGAGTCCCTCCATC





CDS2
NM_003818
465
GGGCTTCTTTGCTACTGTGG
466
ACAGGGCAGACAAAGCATCT





CENPF
NM_016343
469
CTCCCGTCAACAGCGTTC
470
GGGTGAGTCTGGCCTTCA





CHAF1A
NM_005483
473
GAACTCAGTGTATGAGAAGCGG
474
GCTCTGTAGCACCTGCGG





CHN1
NM_001822
477
TTACGACGCTCGTGAAAGC
478
TCTCCCTGATGCACATGTCT





CHRAC1
NM_017444
481
TCTCGCTGCCTCTATCCC
482
CCTGGTTGATGCTGGACA





CKS2
NM_001827
485
GGCTGGACGTGGTTTTGTCT
486
CGCTGCAGAAAATGAAACGA





CLDN3
NM_001306
489
ACCAACTGCGTGCAGGAC
490
GGCGAGAAGGAACAGCAC





CLTC
NM_004859
493
ACCGTATGGACAGCCACAG
494
TGACTACAGGATCAGCGCTTC





COL11A1
NM_001854
497
GCCCAAGAGGGGAAGATG
498
GGACCTGGGTCTCCAGTTG





COL1A1
NM_000088
501
GTGGCCATCCAGCTGACC
502
CAGTGGTAGGTGATGTTCTGGGA





COL1A2
NM_000089
505
CAGCCAAGAACTGGTATAGGAGCT
506
AAACTGGCTGCCAGCATTG





COL3A1
NM_000090
509
GGAGGTTCTGGACCTGCTG
510
ACCAGGACTGCCACGTTC





COL4A1
NM_001845
513
ACAAAGGCCTCCCAGGAT
514
GAGTCCCAGGAAGACCTGCT





COL5A1
NM_000093
517
CTCCCTGGGAAAGATGGC
518
CTGGACCAGGAAGCCCTC





COL5A2
NM_000393
521
GGTCGAGGAACCCAAGGT
522
GCCTGGAGGTCCAACTCTG





COL6A1
NM_001848
525
GGAGACCCTGGTGAAGCTG
526
TCTCCAGGGACACCAACG





COL6A3
NM_004369
529
GAGAGCAAGCGAGACATTCTG
530
AACAGGGAACTGGCCCAC





COL8A1
NM_001850
533
TGGTGTTCCAGGGCTTCT
534
CCCTGTAAACCCTGATCCC





COL9A2
NM_001852
537
GGGAACCATCCAGGGTCT
538
ATTCCGGGTGGACAGTTG





CRISP3
NM_006061
541
TCCCTTATGAACAAGGAGCAC
542
AACCATTGGTGCATAGTCCAT





CSF1
NM_000757
545
TGCAGCGGCTGATTGACA
546
CAACTGTTCCTGGTCTACAAACTCA





CSK
NM_004383
549
CCTGAACATGAAGGAGCTGA
550
CATCACGTCTCCGAACTCC





CSRP1
NM_004078
553
ACCCAAGACCCTGCCTCT
554
GCAGGGGTGGAGTGATGT





CTGF
NM_001901
557
GAGTTCAAGTGCCCTGACG
558
AGTTGTAATGGCAGGCACAG





CTHRC1
NM_138455
561
TGGCTCACTTCGGCTAAAAT
562
TCAGCTCCATTGAATGTGAAA





CTNNA1
NM_001903
565
CGTTCCGATCCTCTATACTGCAT
566
AGGTCCCTGTTGGCCTTATAGG





CTNNB1
NM_001904
569
GGCTCTTGTGCGTACTGTCCTT
570
TCAGATGACGAAGAGCACAGATG





CTNND1
NM_001331
573
CGGAAACTTCGGGAATGTGA
574
CTGAATCCTTCTGCCCAATCTC





CTNND2
NM_001332
577
GCCCGTCCCTACAGTGAAC
578
CTCACACCCAGGAGTCGG





CTSB
NM_001908
581
GGCCGAGATCTACAAAAACG
582
GCAGGAAGTCCGAATACACA





CTSD
NM_001909
585
GTACATGATCCCCTGTGAGAAGGT
586
GGGACAGCTTGTAGCCTTTGC





CTSK
NM_000396
589
AGGCTTCTCTTGGTGTCCATAC
590
CCACCTCTTCACTGGTCATGT





CTSL2
NM_001333
593
TGTCTCACTGAGCGAGCAGAA
594
ACCATTGCAGCCCTGATTG





CTSS
NM_004079
597
TGACAACGGCTTTCCAGTACAT
598
TCCATGGCTTTGTAGGGATAGG





CUL1
NM_003592
601
ATGCCCTGGTAATGTCTGCAT
602
GCGACCACAAGCCTTATCAAG





CXCL12
NM_000609
605
GAGCTACAGATGCCCATGC
606
TTTGAGATGCTTGACGTTGG





CXCR4
NM_003467
609
TGACCGCTTCTACCCCAATG
610
AGGATAAGGCCAACCATGATGT





CXCR7
NM_020311
613
CGCCTCAGAACGATGGAT
614
GTTGCATGGCCAGCTGAT





CYP3A5
NM_000777
617
TCATTGCCCAGTATGGAGATG
618
GACAGGCTTGCCTTTCTCTG





CYR61
NM_001554
621
TGCTCATTCTTGAGGAGCAT
622
GTGGCTGCATTAGTGTCCAT





DAG1
NM_004393
625
GTGACTGGGCTCATGCCT
626
ATCCCACTTGTGCTCCTGTC





DAP
NM_004394
629
CCAGCCTTTCTGGTGCTG
630
GACCAGGTCTGCCTCTGC





DAPK1
NM_004938
633
CGCTGACATCATGAATGTTCCT
634
TCTCTTTCAGCAACGATGTGTCTT





DARC
NM_002036
637
GCCCTCATTAGTCCTTGGCT
638
CAGACAGAAGGGCTGGGAC





DDIT4
NM_019058
641
CCTGGCGTCTGTCCTCAC
642
CGAAGAGGAGGTGGACGA





DDR2
NM_
645
CTATTACCGGATCCAGGGC
646
CCCAGCAAGATACTCTCCCA



001014796









DES
NM_001927
649
ACTTCTCACTGGCCGACG
650
GCTCCACCTTCTCGTTGGT





DHRS9
NM_005771
653
GGAGAAAGGTCTCTGGGGTC
654
CAGTCAGTGGGAGCCAGC





DHX9
NM_001357
657
GTTCGAACCATCTCAGCGAC
658
TCCAGTTGGATTGTGGAGGT





DIAPH1
NM_005219
661
CAAGCAGTCAAGGAGAACCA
662
AGTTTTGCTCGCCTCATCTT





DICER1
NM_177438
665
TCCAATTCCAGCATCACTGT
666
GGCAGTGAAGGCGATAAAGT





DIO2
NM_013989
669
CTCCTTTCACGAGCCAGC
670
AGGAAGTCAGCCACTGAGGA





DLC1
NM_006094
673
GATTCAGACGAGGATGAGCC
674
CACCTCTTGCTGTCCCTTTG





DLGAP1
NM_004746
677
CTGCTGAGCCCAGTGGAG
678
AGCCTGGAAGGAGTTCCG





DLL4
NM_019074
681
CACGGAGGTATAAGGCAGGAG
682
AGAAGGAAGGTCCAGCCG





DNM3
NM_015569
685
CTTTCCCACCCGGCTTAC
686
AAGGACCTTCTGCAGGTGTG





DPP4
NM_001935
689
GTCCTGGGATCGGGAAGT
690
GTACTCCCACCGGGATACAG





DPT
NM_001937
693
CACCTAGAAGCCTGCCCAC
694
CAGTAGCTCCCCAGGGTTC





DUSP1
NM_004417
697
AGACATCAGCTCCTGGTTCA
698
GACAAACACCCTTCCTCCAG





DUSP6
NM_001946
701
CATGCAGGGACTGGGATT
702
TGCTCCTACCCTATCATTTGG





DVL1
NM_004421
705
TCTGTCCCACCTGCTGCT
706
TCAGACTGTTGCCGGATG





DYNLL1
NM_
709
GCCGCCTACCTCACAGAC
710
GCCTGACTCCAGCTCTCCT



001037494









EBNA1BP2
NM_006824
713
TGCGGCGAGATGGACACT
714
GTGACAAGGGATTCATCGGATT





ECE1
NM_001397
717
ACCTTGGGATCTGCCTCC
718
GGACCAGGACCTCCATCTG





EDN1
NM_001955
721
TGCCACCTGGACATCATTTG
722
TGGACCTAGGGCTTCCAAGTC





EDNRA
NM_001957
725
TTTCCTCAAATTTGCCTCAAG
726
TTACACATCCAACCAGTGCC





EFNB2
NM_004093
729
TGACATTATCATCCCGCTAAGGA
730
GTAGTCCCCGCTGACCTTCTC





EGF
NM_001963
733
CTTTGCCTTGCTCTGTCACAGT
734
AAATACCTGACACCCTTATGACAAATT





EGR1
NM_001964
737
GTCCCCGCTGCAGATCTCT
738
CTCCAGCTTAGGGTAGTTGTCCAT





EGR3
NM_004430
741
CCATGTGGATGAATGAGGTG
742
TGCCTGAGAAGAGGTGAGGT





EIF2C2
NM_012154
745
GCACTGTGGGCAGATGAA
746
ATGTTTGGTGACTGGCGG





EIF2S3
NM_001415
749
CTGCCTCCCTGATTCAAGTG
750
GGTGGCAAGTGCCTGTAATATC





EIF3H
NM_003756
753
CTCATTGCAGGCCAGATAAA
754
GCCATGAAGAGCTTGCCTA





EIF4E
NM_001968
757
GATCTAAGATGGCGACTGTCGAA
758
TTAGATTCCGTTTTCTCCTCTTCTG





EIF5
NM_001969
761
GAATTGGTCTCCAGCTGCC
762
TCCAGGTATATGGCTCCTGC





ELK4
NM_001973
765
GATGTGGAGAATGGAGGGAA
766
AGTCATTGCGGCTAGAGGTC





ENPP2
NM_006209
769
CTCCTGCGCACTAATACCTTC
770
TCCCTGGATAATTGGGTCTG





ENY2
NM_020189
773
CCTCAAAGAGTTGCTGAGAGC
774
CCTCTTTACAGTGTGCCTTCA





EPHA2
NM_004431
777
CGCCTGTTCACCAAGATTGAC
778
GTGGCGTGCCTCGAAGTC





EPHA3
NM_005233
781
CAGTAGCCTCAAGCCTGACA
782
TTCGTCCCATATCCAGCG





EPHB2
NM_004442
785
CAACCAGGCAGCTCCATC
786
GTAATGCTGTCCACGGTGC





EPHB4
NM_004444
789
TGAACGGGGTATCCTCCTTA
790
AGGTACCTCTCGGTCAGTGG





ERBB2
NM_004448
793
CGGTGTGAGAAGTGCAGCAA
794
CCTCTCGCAAGTGCTCCAT





ERBB3
NM_001982
797
CGGTTATGTCATGCCAGATACAC
798
GAACTGAGACCCACTGAAGAAAGG





ERBB4
NM_005235
801
TGGCTCTTAATCAGTTTCGTTACCT
802
CAAGGCATATCGATCCTCATAAAGT





ERCC1
NM_001983
805
GTCCAGGTGGATGTGAAAGA
806
CGGCCAGGATACACATCTTA





EREG
NM_001432
809
TGCTAGGGTAAACGAAGGCA
810
TGGAGACAAGTCCTGGCAC





ERG
NM_004449
813
CCAACACTAGGCTCCCCA
814
CCTCCGCCAGGTCTTTAGT





ESR1
NM_000125
817
CGTGGTGCCCCTCTATGAC
818
GGCTAGTGGGCGCATGTAG





ESR2
NM_001437
821
TGGTCCATCGCCAGTTATCA
822
TGTTCTAGCGATCTTGCTTCACA





ETV1
NM_004956
825
TCAAACAAGAGCCAGGAATG
826
AACTGCCAGAGCTGAAGTGA





ETV4
NM_001986
829
TCCAGTGCCTATGACCCC
830
ACTGTCCAAGGGCACCAG





EZH2
NM_004456
833
TGGAAACAGCGAAGGATACA
834
CACCGAACACTCCCTAGTCC





F2R
NM_001992
837
AAGGAGCAAACCATCCAGG
838
GCAGGGTTTCATTGAGCAC




















FAH
NM_001441
841
GACAGCGTAGTGGTGCATGT
842
AGCTGAACATGGACTGTGGA





FABP5
NM_001444
845
GCTGATGGCAGAAAAACTCA
846
CTTTCCTTCCCATCCCACT





FADD
NM_003824
849
GTTTTCGCGAGATAACGGTC
850
CTCCGGTGCCTGATTCAC





FAM107A
NM_007177
853
AAGTCAGGGAAAACCTGCG
854
GCTGGCCCTACAGCTCTCT





FAM13C
NM_198215
857
ATCTTCAAAGCGGAGAGCG
858
GCTGGATACCACATGCTCTG





FAM171B
NM_177454
861
CCAGGAAGGAAAAGCACTGT
862
GTGGTCTGCCCCTTCTTTTA





FAM49B
NM_016623
865
AGATGCAGAAGGCATCTTGG
866
GCTGGATTGCCTCTCGTATT





FAM73A
NM_198549
869
TGAGAAGGTGCGCTATTCAA
870
GGCCATTAAAAGCTCAGTGC





FAP
NM_004460
873
GTTGGCTCACGTGGGTTAC
874
GACAGGACCGAAACATTCTG





FAS
NM_000043
877
GGATTGCTCAACAACCATGCT
878
GGCATTAACACTTTTGGACGATAA





FASLG
NM_000639
881
GCACTTTGGGATTCTTTCCATTAT
882
GCATGTAAGAAGACCCTCACTGAA





FASN
NM_004104
885
GCCTCTTCCTGTTCGACG
886
GCTTTGCCCGGTAGCTCT





FCGR3A
NM_000569
889
GTCTCCAGTGGAAGGGAAAA
890
AGGAATGCAGCTACTCACTGG





FGF10
NM_004465
893
TCTTCCGTCCCTGTCACCT
894
AGAGTTGGTGGCCTCTGGT





FGF17
NM_003867
897
GGTGGCTGTCCTCAAAATCT
898
TCTAGCCAGGAGGAGTTTGG





FGF5
NM_004464
901
GCATCGGTTTCCATCTGC
902
AACATATTGGCTTCGTGGGA





FGF6
NM_020996
905
GGGCCATTAATTCTGACCAC
906
CCCGGGACATAGTGATGAA





FGF7
NM_002009
909
CCAGAGCAAATGGCTACAAA
910
TCCCCTCCTTCCATGTAATC





FGFR2
NM_000141
913
GAGGGACTGTTGGCATGCA
914
GAGTGAGAATTCGATCCAAGTCTTC





FGFR4
NM_002011
917
CTGGCTTAAGGATGGACAGG
918
ACGAGACTCCAGTGCTGATG





FKBP5
NM_004117
921
CCCACAGTAGAGGGGTCTCA
922
GGTTCTGGCTTTCACGTCTG





FLNA
NM_001456
925
GAACCTGCGGTGGACACT
926
GAAGACACCCTGGCCCTC





FLNC
NM_001458
929
CAGGACAATGGTGATGGCT
930
TGATGGTGTACTCGCCAGG





FLT1
NM_002019
933
GGCTCCTGAATCTATCTTTG
934
TCCCACAGCAATACTCCGTA





FLT4
NM_002020
937
ACCAAGAAGCTGAGGACCTG
938
CCTGGAAGCTGTAGCAGACA





FN1
NM_002026
941
GGAAGTGACAGACGTGAAGGT
942
ACACGGTAGCCGGTCACT





FOS
NM_005252
945
CGAGCCCTTTGATGACTTCCT
946
GGAGCGGGCTGTCTCAGA





FOXO1
NM_002015
949
GTAAGCACCATGCCCCAC
950
GGGGCAGAGGCACTTGTA





FOXP3
NM_014009
953
CTGTTTGCTGTCCGGAGG
954
GTGGAGGAACTCTGGGAATG





FOXQ1
NM_033260
957
TGTTTTTGTCGCAACTTCCA
958
TGGAAAGGTTCCCTGATGTACT





FSD1
NM_024333
961
AGGCCTCCTGTCCTTCTACA
962
TGTGTGAACCTGGTCTTGAAA





FYN
NM_002037
965
GAAGCGCAGATCATGAAGAA
966
CTCCTCAGACACCACTGCAT





G6PD
NM_000402
969
AATCTGCCTGTGGCCTTG
970
CGAGATGTTGCTGGTGACA





GABRG2
NM_198904
973
CCACTGTCCTGACAATGACC
974
GAGATCCATCGCTGTGACAT





GADD45A
NM_001924
977
GTGCTGGTGACGAATCCA
978
CCCGGCAAAAACAAATAAGT





GADD45B
NM_015675
981
ACCCTCGACAAGACCACACT
982
TGGGAGTTCATGGGTACAGA





GDF15
NM_004864
985
CGCTCCAGACCTATGATGACT
986
ACAGTGGAAGGACCAGGACT





GHR
NM_000163
989
CCACCTCCCACAGGTTCA
990
GGTGCGTGCCTGTAGTCC





GNPTAB
NM_024312
993
GGATTCACATCGCGGAAA
994
GTTCTTGCATAACAATCCGGTC





GNRH1
NM_000825
997
AAGGGCTAAATCCAGGTGTG
998
CTGGATCTCTGTGGCTGGT





GPM6B
NM_
1001
ATGTGCTTGGAGTGGCCT
1002
TGTAGAACATAAACACGGGCA



001001994









GPNMB
NM_
1005
CAGCCTCGCCTTTAAGGAT
1006
TGACAAATATGGCCAAGCAG



001005340









GPR68
NM_003485
1009
CAAGGACCAGATCCAGCG
1010
GGTAGGGCAGGAAGCAGG





GPS1
NM_004127
1013
AGTACAAGCAGGCTGCCAAG
1014
GCAGCTCAGGGAAGTCACA





GRB7
NM_005310
1017
CCATCTGCATCCATCTTGTT
1018
GGCCACCAGGGTATTATCTG





GREM1
NM_013372
1021
GTGTGGGCAAGGACAAGC
1022
GACCTGATTTGGCCTCACC





GSK3B
NM_002093
1025
GACAAGGACGGCAGCAAG
1026
TTGTGGCCTGTCTGGACC





GSN
NM_000177
1029
CTTCTGCTAAGCGGTACATCGA
1030
GGCTCAAAGCCTTGCTTCAC





GSTM1
NM_000561
1033
AAGCTATGAGGAAAAGAAGTACACGA
1034
GGCCCAGCTTGAATTTTTCA





T







GSTM2
NM_000848
1037
CTGCAGGCACTCCCTGAAAT
1038
CCAAGAAACCATGGCTGCTT





HDAC1
NM_004964
1041
CAAGTACCACAGCGATGACTACATTA
1042
GCTTGCTGTACTCCGACATGTT





A







HDAC9
NM_178423
1045
AACCAGGCAGTCACCTTGAG
1046
CTCTGTCTTCCTGCATCGC





HGD
NM_000187
1049
CTCAGGTCTGCCCCTACAAT
1050
TTATTGGTGCTCCGTGGAC





HIP1
NM_005338
1053
CTCAGAGCCCCACCTGAG
1054
GGGTTTCCCTGCCATACTG





HIRIP3
NM_003609
1057
GGATGAGGAAAAGGGGGAT
1058
TCCCTAGCTGACTTTCTCCG





HK1
NM_000188
1061
TACGCACAGAGGCAAGCA
1062
GAGAGAAGTGCTGGAGAGGC





HLA-G
NM_002127
1065
CCATCCCCATCATGGGTATC
1066
CCGCAGCTCCAGTGACTACA





HLF
NM_002126
1069
CACCCTGCAGGTGTCTGAG
1070
GGTACCTAGGAGCAGAAGGTGA





HNF1B
NM_000458
1073
TCCCAGCATCTCAACAAGG
1074
CGTACCAGGTGTACAGAGCG





HPS1
NM_000195
1077
GCGGAAGCTGTATGTGCTC
1078
TTCGGATAAGATGACCGTCC





HRAS
NM_005343
1081
GGACGAATACGACCCCACT
1082
GCACGTCTCCCCATCAAT





HSD17B10
NM_004493
1085
CCAGCGAGTTCTTGATGTGA
1086
ATCTCACCAGCCACCAGG





HSD17B2
NM_002153
1089
GCTTTCCAAGTGGGGAATTA
1090
TGCCTGCGATATTTGTTAGG





HSD17B3
NM_000197
1093
GGGACGTCCTGGAACAGT
1094
TGGAGAATCTCACGCACTTC





HSD17B4
NM_000414
1097
CGGGAAGCTTCAGAGTACCTT
1098
ACCTCAGGCCCAATATCCTT





HSD3B2
NM_000198
1101
GCCTTCCTTTAACCCTGATG
1102
GGAGTAAATTGGGCTGAGTAGG





HSP90AB1
NM_007355
1105
GCATTGTGACCAGCACCTAC
1106
GAAGTGCCTGGGCTTTCAT





HSPA5
NM_005347
1109
GGCTAGTAGAACTGGATCCCAACA
1110
GGTCTGCCCAAATGCTTTTC





HSPA8
NM_006597
1113
CCTCCCTCTGGTGGTGCTT
1114
GCTACATCTACACTTGGTTGGCTTAA





HSPB1
NM_001540
1117
CCGACTGGAGGAGCATAAA
1118
ATGCTGGCTGACTCTGCTC





HSPB2
NM_001541
1121
CACCACTCCAGAGGTAGCAG
1122
TGGGACCAAACCATACATTG





HSPE1
NM_002157
1125
GCAAGCAACAGTAGTCGCTG
1126
CCAACTTTCACGCTAACTGGT





HSPG2
NM_005529
1129
GAGTACGTGTGCCGAGTGTT
1130
CTCAATGGTGACCAGGACA





ICAM1
NM_000201
1133
GCAGACAGTGACCATCTACAGCTT
1134
CTTCTGAGACCTCTGGCTTCGT





IER3
NM_003897
1137
GTACCTGGTGCGCGAGAG
1138
GCGTCTCCGCTGTAGTGTT





IFI30
NM_006332
1141
ATCCCATGAAGCCCAGATAC
1142
GCACCATTCTTAGTGGAGCA





IFIT1
NM_001548
1145
TGACAACCAAGCAAATGTGA
1146
CAGTCTGCCCATGTGGTAAT





IFNG
NM_000619
1149
GCTAAAACAGGGAAGCGAAA
1150
CAACCATTACTGGGATGCTC





IGF1
NM_000618
1153
TCCGGAGCTGTGATCTAAGGA
1154
CGGACAGAGCGAGCTGACTT





IGF1R
NM_000875
1157
GCATGGTAGCCGAAGATTTCA
1158
TTTCCGGTAATAGTCTGTCTCATAGATA







TC





IGF2
NM_000612
1161
CCGTGCTTCCGGACAACTT
1162
TGGACTGCTTCCAGGTGTCA





IGFBP2
NM_000597
1165
GTGGACAGCACCATGAACA
1166
CCTTCATACCCGACTTGAGG





IGFBP3
NM_000598
1169
ACATCCCAACGCATGCTC
1170
CCACGCCCTTGTTTCAGA





IGFBP5
NM_000599
1173
TGGACAAGTACGGGATGAAGCT
1174
CGAAGGTGTGGCACTGAAAGT





IGKBP6
NM_002178
1177
TGAACCGCAGAGACCAACAG
1178
GTCTTGGACACCCGCAGAAT





IL10
NM_000572
1181
CTGACCACGCTTTCTAGCTG
1182
CCAAGCCCAGAGACAAGATAA





IL11
NM_000641
1185
TGGAAGGTTCCACAAGTCAC
1186
TCTTGACCTTGCAGCTTTGT





IL17A
NM_002190
1189
TCAAGCAACACTCCTAGGGC
1190
CAGCTCCTTTCTGGGTTGTG





IL1A
NM_000575
1193
GGTCCTTGGTAGAGGGCTACTT
1194
GGATGGAGCTTCAGGAGAGA





IL1B
NM_000576
1197
AGCTGAGGAAGATGCTGGTT
1198
GGAAAGAAGGTGCTCAGGTC





IL2
NM_000586
1201
ACCTCAACTCCTGCCACAAT
1202
CACTGTTTGTGACAAGTGCAAG





IL6
NM_000600
1205
CCTGAACCTTCCAAAGATGG
1206
ACCAGGCAAGTCTCCTCATT





IL6R
NM_000565
1209
CCAGCTTATCTCAGGGGTGT
1210
CTGGCGTAGAACCTTCCG





IL6ST
NM_002184
1213
GGCCTAATGTTCCAGATCCT
1214
AAAATTGTGCCTTGGAGGAG





IL8
NM_000584
1217
AAGGAACCATCTCACTGTGTGTAAAC
1218
ATCAGGAAGGCTGCCAAGAG





ILF3
NM_004516
1221
GACACGCCAAGTGGTTCC
1222
CTCAAGACCCGGATCACAA





ILK
NM_
1225
CTCAGGATTTTCTCGCATCC
1226
AGGAGCAGGTGGAGACTGG



001014794









IMMT
NM_006839
1229
CTGCCTATGCCAGACTCAGA
1230
GCTTTTCTGGCTTCCTCTTC





ING5
NM_032329
1233
CCTACAGCAAGTGCAAGGAA
1234
CATCTCGTAGGTCTGCATGG





INHBA
NM_002192
1237
GTGCCCGAGCCATATAGCA
1238
CGGTAGTGGTTGATGACTGTTGA





INSL4
NM_002195
1241
CTGTCATATTGCCCCATGC
1242
CAGATTCCAGCAGCCACC





ITGA1
NM_181501
1245
GCTTCTTCTGGAGATGTGCTCT
1246
CCTGTAGATAATGACCTGGCCT





ITGA3
NM_002204
1249
CCATGATCCTCACTCTGCTG
1250
GAAGCTTTGTAGCCGGTGAT





ITGA4
NM_000885
1253
CAACGCTTCAGTGATCAATCC
1254
GTCTGGCCGGGATTCTTT





ITGA5
NM_002205
1257
AGGCCAGCCCTACATTATCA
1258
GTCTTCTCCACAGTCCAGCA





ITGA6
NM_000210
1261
CAGTGACAAACAGCCCTTCC
1262
GTTTAGCCTCATGGGCGTC





ITGA7
NM_002206
1265
GATATGATTGGTCGCTGCTTTG
1266
AGAACTTCCATTCCCCACCAT





ITGAD
NM_005353
1269
GAGCCTGGTGGATCCCAT
1270
ACTGTCAGGATGCCCGTG





ITGB3
NM_000212
1273
ACCGGGAGCCCTACATGAC
1274
CCTTAAGCTCTTTCACTGACTCAATCT





ITGB4
NM_000213
1277
CAAGGTGCCCTCAGTGGA
1278
GCGCACACCTTCATCTCAT





ITGB5
NM_002213
1281
TCGTGAAAGATGACCAGGAG
1282
GGTGAACATCATGACGCAGT





ITPR1
NM_002222
1285
GAGGAGGTGTGGGTGTTCC
1286
GTAATCCCATGTCCGCGA





ITPR3
NM_002224
1289
TTGCCATCGTGTCAGTGC
1290
ATGGAGCTGGCGTCATTG





ITSN1
NM_003024
1293
TAACTGGGATGCATGGGC
1294
CTCTGCCTTAACTGGCCG





JAG1
NM_000214
1297
TGGCTTACACTGGCAATGG
1298
GCATAGCTGTGAGATGCGG





JUN
NM_002228
1301
GACTGCAAAGATGGAAACGA
1302
TAGCCATAAGGTCCGCTCTC





JUNB
NM_002229
1305
CTGTCAGCTGCTGCTTGG
1306
AGGGGGTGTCCGTAAAGG





KCNN2
NM_021614
1309
TGTGCTATTCATCCCATACCTG
1310
GGGCATAGGAGAAGGCAAG





KCTD12
NM_138444
1313
AGCAGTTACTGGCAAGAGGG
1314
TGGAGACCTGAGCAGCCT





KNDRBS3
NM_006558
1317
CGGGCAAGAAGAGTGGAC
1318
CTGTAGACGCCCTTTGCTGT





KIAA0196
NM_014846
1321
CAGACACCAGCTCTGAGGC
1322
AACATTGTGAGGCGGACC





KIAA0247
NM_014734
1325
CCGTGGGACATGGAGTGT
1326
GAAGCAAGTCCGTCTCCAAG





KF4A
NM_012310
1329
AGAGCTGGTCTCCTCCAAAA
1330
GCTGGTCTTGCTCTGTTTCA





KIT
NM_000222
1333
GAGGCAACTGCTTATGGCTTAATTA
1334
GGCACTCGGCTTGAGCAT





KLC1
NM_182923
1337
AGTGGCTACGGGATGAACTG
1338
TGAGCCACAGACTGCTCACT





KLF6
NM_001300
1341
CACGAGACCGGCTACTTCTC
1342
GCTCTAGGCAGGTCTGTTGC





KLK1
NM_002257
1345
AACACAGCCCAGTTTGTTCA
1346
CCAGGAGGCTCATGTTGAAG





KLK10
NM_002776
1349
GCCCAGAGGCTCCATCGT
1350
CAGAGGTTTGAACAGTGCAGACA





KLK11
NM_006853
1353
CACCCCGGCTTCAACAAC
1354
CATCTTCACCAGCATGATGTCA





KLK14
NM_022046
1357
CCCCTAAAATGTTCCTCCTG
1358
CTCATCCTCTTGGCTCTGTG





KLK2
NM_005551
1361
AGTCTCGGATTGTGGGAGG
1362
TGTACACAGCCACCTGCC





KLK3
NM_001648
1365
CCAAGCTTACCACCTGCAC
1366
AGGGTGAGGAAGACAACCG





KLRK1
NM_007360
1369
TGAGAGCCAGGCTTCTTGTA
1370
ATCCTGGTCCTCTTTGCTGT





KPNA2
NM_002266
1373
TGATGGTCCAAATGAACGAA
1374
AAGCTTCACAAGTTGGGGC





KRT1
NM_006121
1377
TGGACAACAACCGCAGTC
1378
TATCCTCGTACTGGGCCTTG





KRT15
NM_002275
1381
GCCTGGTTCTTCAGCAAGAC
1382
CTTGCTGGTCTGGATCATTTC





KRT18
NM_000224
1385
AGAGATCGAGGCTCTCAAGG
1386
GGCCTTTTACTTCCTCTTCG





KRT2
NM_000423
1389
CCAGTGACGCCTCTGTGTT
1390
GGGCATGGCTAGAAGCAC





KRT5
NM_000424
1393
TCAGTGGAGAAGGAGTTGGA
1394
TGCCATATCCAGAGGAAACA





KRT75
NM_004693
1397
TCAAAGTCAGGTACGAAGATGAAATT
1398
ACGTCCTTTTTCAGGGCTACAA





KRT76
NM_015848
1401
ATCTCCAGACTGCTGGTTCC
1402
TCAGGGAATTAGGGGACAGA





KRT8
NM_002273
1405
GGATGAAGCTTACATGAACAAGGTAG
1406
CATATAGCTGCCTGAGGAAGTTGAT





A







L1CAM
NM_000425
1409
CTTGCTGGCCAATGCCTA
1410
TGATTGTCCGCAGTCAGG





LAG3
NM_002286
1413
GCCTTAGAGCAAGGGATTCA
1414
CGGTTCTTGCTCCAGCTC





LAMA3
NM_000227
1417
CCTGTCACTGAAGCCTTGG
1418
TGGGTTACTGGTCAGGACAAC





LAMA4
NM_002290
1421
GATGCACTGCGGTTAGCAG
1422
CAGAGGATACGCTCAGCACC





LAMA5
NM_005560
1425
CTCCTGGCCAACAGCACT
1426
ACACAAGGCCCAGCCTCT





LAMB1
NM_002291
1429
CAAGGAGACTGGGAGGTGTC
1430
CGGCAGAACTGACAGTGTTC





LAMB3
NM_000228
1433
ACTGACCAAGCCTGAGACCT
1434
GTCACACTTGCAGCATTTCA





LAMC1
NM_002293
1437
GCCGTGATCTCAGACAGCTAC
1438
ACCTGCTTGCCCAAGAACT





LAMC2
NM_005562
1441
ACTCAAGCGGAAATTGAAGCA
1442
ACTCCCTGAAGCCGAGACACT





LAPTM5
NM_006762
1445
TGCTGGACTTCTGCCTGAG
1446
TGAGATAGGTGGGCACTTCC





LGALS3
NM_002306
1449
AGCGGAAAATGGCAGACAAT
1450
CTTGAGGGTTTGGGTTTCCA





LIG3
NM_002311
1453
GGAGGTGGAGAAGGAGCC
1454
ACAGGTGTCATCAGCGAGG





LIMS1
NM_004987
1457
TGAACAGTAATGGGGAGCTG
1458
TTCTGGGAACTGCTGGAAG





LOX
NM_002317
1461
CCAATGGGAGAACAACGG
1462
CGCTGAGGCTGGTACTGTG





LRP1
NM_002332
1465
TTTGGCCCAATGGGCTAAG
1466
GTCTCGATGCGGTCGTAGAAG





LTBP2
NM_000428
1469
GCACACCCATCCTTGAGTCT
1470
GATGGCTGGCCACGTAGT





LUM
NM_002345
1473
GGCTCTTTTGAAGGATTGGTAA
1474
AAAAGCAGCTGAAACAGCATC





MAGEA4
NM_002362
1477
GCATCTAACAGCCCTGTGC
1478
CAGAGTGAAGAATGGGCCTC





MANF
NM_006010
1481
CAGATGTGAAGCCTGGAGC
1482
AAGGGAATCCCCTCATGG





MAOA
NM_000240
1485
GTGTCAGCCAAAGCATGGA
1486
CGACTACGTCGAACATGTGG





MAP3K5
NM_005923
1489
AGGACCAAGAGGCTACGGA
1490
CCTGTGGCCATTTCAATGAT





MAP3K7
NM_145333
1493
CAGGCAAGAACTAGTTGCAGAA
1494
CCTGTACCAGGCGAGATGTAT





MAP4K4
NM_004834
1497
TCGCCGAGATTTCCTGAG
1498
CTGTTGTCTCCGAAGAGCCT





MAP7
NM_003980
1501
GAGGAACAGAGGTGTCTGCAC
1502
CTGCCAACTGGCTTTCCA





MAPKAPK3
NM_004635
1505
AAGCTGCAGAGATAATGCGG
1506
GTGGGCAATGTTATGGCTG





MCM2
NM_004526
1509
GACTTTTGCCCGCTACCTTTC
1510
GCCACTAACTGCTTCAGTATGAAGAG





MCM3
NM_002388
1513
GGAGAACAATCCCCTTGAGA
1514
ATCTCCTGGATGGTGATGGT





MCM6
NM_005915
1517
TGATGGTCCTATGTGTCACATTCA
1518
TGGGACAGGAAACACACCAA





MDK
NM_002391
1521
GGAGCCGACTGCAAGTACA
1522
GACTTTGGTGCCTGTGCC





MDM2
NM_002392
1525
CTACAGGGACGCCATCGAA
1526
ATCCAACCAATCACCTGAATGTT





MELK
NM_014791
1529
AGGATCGCCTGTCAGAAGAG
1530
TGCACATAAGCAACAGCAGA





MET
NM_000245
1533
GACATTTCCAGTCCTGCAGTCA
1534
CTCCGATCGCACACATTTGT





MGMT
NM_002412
1537
GTGAAATGAAACGCACCACA
1538
GACCCTGCTCACAACCAGAC





MGST1
NM_020300
1541
ACGGATCTACCACACCATTGC
1542
TCCATATCCAACAAAAAAACTCAAAG





MICA
NM_000247
1545
ATGGTGAATGTCACCCGC
1546
AAGCCAGAAGCCCTGCAT





MKI67
NM_002417
1549
GATTGCACCAGGGCAGAA
1550
TCCAAAGTGCCTCTGCTAAGA





MLXIP
NM_014938
1553
TGCTTAGCTGGCATGTGG
1554
CAGCCTACTCTCCATGGGC





MMP11
NM_005940
1557
CCTGGAGGCTGCAACATACC
1558
TACAATGGCTTTGGAGGATAGCA





MMP2
NM_004530
1561
CAGCCAGAAGCGGAAACTTA
1562
AGACACCATCACCTGTGCC





MMP7
NM_002423
1565
GGATGGTAGCAGTCTAGGGATTAACT
1566
GGAATGTCCCATACCCAAAGAA





MMP9
NM_004994
1569
GAGAACCAATCTCACCGACA
1570
CACCCGAGTGTAACCATAGC





MPPED2
NM_001584
1573
CCGACCAACCCTCCAATTA
1574
AGGGCATTTAGAGCTTCAGGA





MRC1
NM_002438
1577
CTTGACCTCAGGACTCTGGATT
1578
GGACTGCGGTCACTCCAC





MRPL13
NM_014078
1581
TCCGGTTCCCTTCGTTTAG
1582
GTGGAAAAACTGCGGAAAAC





MSH2
NM_000251
1585
GATGCAGAATTGAGGCAGAC
1586
TCTTGGCAAGTCGGTTAAGA





MSH3
NM_002439
1589
TGATTACCATCATGGCTCAGA
1590
CTTGTGAAAATGCCATCCAC





MSH6
NM_000179
1593
TCTATTGGGGGATTGGTAGG
1594
CAAATTGCGAGTGGTGAAAT





MTA1
NM_004689
1597
CCGCCCTCACCTGAAGAGA
1598
GGAATAAGTTAGCCGCGCTTCT





MTPN
NM_145808
1601
GGTGGAAGGAAACCTCTTCA
1602
CAGCAGCAGAAATTCCAGG





MTSS1
NM_014751
1605
TTCGACAAGTCCTCCACCAT
1606
CTTGGAACATCCGTCGGTAG





MUC1
NM_002456
1609
GGCCAGGATCTGTGGTGGTA
1610
CTCCACGTCGTGGACATTGA





MVP
NM_017458
1613
ACGAGAACGAGGGCATCTATGT
1614
GCATGTAGGTGCTTCCAATCAC





MYBL2
NM_002466
1617
GCCGAGATCGCCAAGATG
1618
CTTTTGATGGTAGAGTTCCAGTGATTC





MYBPC1
NM_002465
1621
CAGCAACCAGGGAGTCTGTA
1622
CAGCAGTAAGTGCCTCCATC





MYC
NM_002467
1625
TCCCTCCACTCGGAAGGACTA
1626
CGGTTGTTGCTGATCTGTCTCA





MYLK3
NM_182493
1629
CACCTGACTGAGCTGGATGT
1630
GATGTAGTGCTGGTGCAGGT





MYO6
NM_004999
1633
AAGCAGTTCTGGAGCAGGAG
1634
GATGAGCTCGGCTTCACTCT





NCAM1
NM_000615
1637
TAGTTCCCAGCTGACCATCA
1638
CAGCCTTGTTCTCAGCAATG





NCAPD3
NM_015261
1641
TCGTTGCTTAGACAAGGCG
1642
CTCCAGACAGTGTGCAAAGC





NCOR1
NM_006311
1645
AACCGTTACAGCCCAGAATC
1646
TCTGGAGAGACCCTTGAACC





NCOR2
NM_006312
1649
CGTCATCTACGAAGGCAAGA
1650
GAGCACTGGGTCACAGACAT





NDRG1
NM_006096
1653
AGGGCAACATTCCACAGC
1654
CAGTGCTCCTACTCCGGC





NDUFS5
NM_004552
1657
AGAAGAGTCAAGGGCACGAG
1658
AGGCCGAACCTTTTCTGG





NEK2
NM_002497
1661
GTGAGGCAGCGCGACTCT
1662
TGCCAATGGTGTACAACACTTCA





NETO2
NM_018092
1665
CCAGGGCACCATACTGTTTC
1666
AACGGTAAATCAAGGTCTTCGT





NEXN
NM_144573
1669
AGGAGGAGGAAGAAGGTAGCA
1670
GAGCTCCTGATCTGGTTTGC





NFAT5
NM_006599
1673
CTGAACCCCTCTCCTGGTC
1674
AGGAAACGATGGCGAGGT





NFATC2
NM_173091
1677
CAGTCAAGGTCAGAGGCTGAG
1678
CTTTGGCTCGTGGCATTC





NFKB1
NM_003998
1681
CAGACCAAGGAGATGGACCT
1682
AGCTGCCAGTGCTATCCG





NFKBIA
NM_020529
1685
CTACTGGACGACCGCCAC
1686
CCTTGACCATCTGCTCGTACT





NME1
NM_000269
1689
CCAACCCTGCAGACTCCAA
1690
ATGTATAATGTTCCTGCCAACTTGTATG





NNMT
NM_006169
1693
CCTAGGGCAGGGATGGAG
1694
CTAGTCCAGCCAAACATCCC





NOS3
NM_000603
1697
ATCTCCGCCTCGCTCATG
1698
TCGGAGCCATACAGGATTGTC





NOX4
NM_016931
1701
CCTCAACTGCAGCCTTATCC
1702
TGCTTGGAACCTTCTGTGAT





NPBWR1
NM_005285
1705
TCACCAACCTGTTCATCCTC
1706
GATGTTGATGGGCAGCAC





NPM1
NM_002520
1709
AATGTTGTCCAGGTTCTATTGC
1710
CAAGCAAAGGGTGGAGTTC





NRG1
NM_013957
1713
CGAGACTCTCCTCATAGTGAAAGGTA
1714
CTTGGCGTGTGGAAATCTACAG





T







NRIP3
NM_020645
1717
CCCACAAGCATGAAGGAGA
1718
TGCTCAATCTGGCCCACTA





NRP1
NM_003873
1721
CAGCTCTCTCCACGCGATTC
1722
CCCAGCAGCTCCATTCTGA





NUP62
NM_153719
1725
AGCCTCTTTGCGTCAATAGC
1726
CTGTGGTCACAGGGGTACAG





OAZ1
NM_004152
1729
AGCAAGGACAGCTTTGCAGT
1730
GAAGACATGGTCGGCTCG





OCLN
NM_002538
1733
CCCTCCCATCCGAGTTTC
1734
GACGCGGGAGTGTAGGTG





ODC1
NM_002539
1737
AGAGATCACCGGCGTAATCAA
1738
CGGGCTCAGCTATGATTCTCA





OLFML2B
NM_015441
1741
CATGTTGGAAGGAGCGTTCT
1742
CACCAGTTTGGTGGTGACTG





OLFML3
NM_020190
1745
TCAGAACTGAGGCCGACAC
1746
CCAGATAGTCTACCTCCCGCT





OMD
NM_005014
1749
CGCAAACTCAAGACTATCCCA
1750
CAGTCACAGCCTCAATTTCATT





OR51E1
NM_152430
1753
GCATGCTTTCAGGCATTGA
1754
AGAAGATGGCCAGCATTTTG





OR51E2
NM_030774
1757
TATGGTGCCAAAACCAAACA
1758
GTCCTTGTCACAGCTGATCTTG





OSM
NM_020530
1761
GTTTCTGAAGGGGAGGTCAC
1762
AGGTGTCTGGTTTGGGACA





PAGE1
NM_003785
1765
CAACCTGACGAAGTGGAATC
1766
CAGATGCTCCCTCATCCTCT





PAGE4
NM_007003
1769
GAATCTCAGCAAGAGGAACCA
1770
GTTCTTCGATCGGAGGTGTT





PAK6
NM_020168
1773
CCTCCAGGTCACCCACAG
1774
GTCCCTTCAGGCCAGAACTT





PATE1
NM_138294
1777
TGGTAATCCCTGGTTAACCTTC
1778
TCCACCTTATGCCTTTCACA





PCA3
NR_015342
1781
CGTGATTGTCAGGAGCAAGA
1782
AGAAAGGGGAGATGCAGAGG





PCDHGB7
NM_018927
1785
CCCAGCGTTGAAGCAGAT
1786
GAAACGCCAGTCCGTGTT





PCNA
NM_002592
1789
GAAGGTGTTGGAGGCACTCAAG
1790
GGTTTACACCGCTGGAGCTAA





PDE9A
NM_
1793
TTCCACAACTTCCGGCAC
1794
AGACTGCAGAGCCAGACCA



001001570









PDGFRB
NM_002609
1797
CCAGCTCTCCTTCCAGCTAC
1798
GGGTGGCTCTCACTTAGCTC





PECAM1
NM_000442
1801
TGTATTTCAAGACCTCTGTGCACTT
1802
TTAGCCTGAGGAATTGCTGTGTT





PEX10
NM_153818
1805
GGAGAAGTTCCCTCCCCAG
1806
ATCTGTGTCCAGGCCCAC





PGD
NM_002631
1809
ATTCCCATGCCCTGTTTTAC
1810
CTGGCTGGAAGCATCTCAT





PGF
NM_002632
1813
GTGGTTTTCCCTCGGAGC
1814
AGCAAGGGAACAGCCTCAT





PGK1
NM_000291
1817
AGAGCCAGTTGCTGTAGAACTCAA
1818
CTGGGCCTACACAGTCCTTCA





PGR
NM_000926
1821
GATAAAGGAGCCGCGTGTCA
1822
TCACAAGTCCGGCACTTGAG





PHTF2
NM_020432
1825
GATATGGCTGATGCTGCTCC
1826
GGTTTGGGTGTTCTTGTGGA





PIK3C2A
NM_002645
1829
ATACCAATCACCGCACAAACC
1830
CACACTAGCATTTTCTCCGCATA





PIK3CA
NM_006218
1833
GTGATTGAAGAGCATGCCAA
1834
GTCCTGCGTGGGAATAGC





PIK3CG
NM_002649
1837
GGAGAACTCAATGTCCATCTCC
1838
TGATGCTTAGGCAGGGCT





PIM1
NM_002648
1841
CTGCTCAAGGACACCGTCTA
1842
GGATCCACTCTGGAGGGC





PLA2G7
NM_005084
1845
CCTGGCTGTGGTTTATCCTT
1846
TGACCCATGCTGATGATTTC





PLAU
NM_002658
1849
GTGGATGTGCCCTGAAGGA
1850
CTGCGGATCCAGGGTAAGAA





PLAUR
NM_002659
1853
CCCATGGATGCTCCTCTGAA
1854
CCGGTGGCTACCAGACATTG





PLG
NM_000301
1857
GGCAAAATTTCCAAGACCAT
1858
ATGTATCCATGAGCGTGTGG





PLK1
NM_005030
1861
AATGAATACAGTATTCCCAAGCACAT
1862
TGTCTGAAGCATCTTCTGGATGA





PLOD2
NM_000935
1865
CAGGGAGGTGGTTGCAAAT
1866
TCTCCCAGGATGCATGAAG





PLP2
NM_002668
1869
CCTGATCTGCTTCAGTGCC
1870
GCAGCAAGGATCATCTCAATC





PNLIPRP2
NM_005396
1873
TGGAGAAGGTGAACTGCATC
1874
CACGGCTTGGGTGTACATT





POSTN
NM_006475
1877
GTGGCCCAATTAGGCTTG
1878
TCACAGGTGCCAGCAAAG





PPAP2B
NM_003713
1881
ACAAGCACCATCCCAGTGA
1882
CACGAAGAAAACTATGCAGCAG





PPFIA3
NM_003660
1885
CCTGGAGCTCCGTTACTCTC
1886
AGCCACATAGGGATCCAGG





PPP1R12A
NM_002480
1889
CGGCAAGGGGTTGATATAGA
1890
TGCCTGGCATCTCTAAGCA





PPP3CA
NM_000944
1893
ATACTCCGAGCCCACGAA
1894
GGAAGCCTGTTGTTTGGC





PRIMA1
NM_178013
1897
ATCCTCTTCCCTGAGCCG
1898
CCCAGCTGAGAGGGAATTTA





PRKAR1B
NM_002735
1901
ACAAAACCATGACTGCGCT
1902
TGTCATCCAGGTGAGCGA





PRKAR2B
NM_002736
1905
TGATAATCGTGGGAGTTTCG
1906
GCACCAGGAGAGGTAGCAGT





PRKCA
NM_002737
1909
CAAGCAATGCGTCATCAATGT
1910
GTAAATCCGCCCCCTCTTCT





PRKCB
NM_002738
1913
GACCCAGCTCCACTCCTG
1914
CCCATTCACGTACTCCATCA





PROM1
NM_006017
1917
CTATGACAGGCATGCCACC
1918
CTCCAACCATGAGGAAGACG





PROS1
NM_000313
1921
GCAGCACAGGAATCTTCTTCTT
1922
CCCACCTATCCAACCTAATCTG





PSCA
NM_005672
1925
ACCGTCATCAGCAAAGGCT
1926
CGTGATGTTCTTCTTGCCC





PSMD13
NM_002817
1929
GGAGGAGCTCTACACGAAGAAG
1930
CGGATCCTGCACAAAATCA





PTCH1
NM_000264
1933
CCACGACAAAGCCGACTAC
1934
TACTCGATGGGCTCTGCTG





PTEN
NM_000314
1937
TGGCTAAGTGAAGATGACAATCATG
1938
TGCACATATCATTACACCAGTTCGT





PTGER3
NM_000957
1941
TAACTGGGGCAACCTTTTCT
1942
TTGCAGGAAAAGGTGACTGT





PTGS2
NM_000963
1945
GAATCATTCACCAGGCAAATTG
1946
CTGTACTGCGGGTGGAACAT





PTH1R
NM_000316
1949
CGAGGTACAAGCTGAGATCAAGAA
1950
GCGTGCCTTTCGCTTGAA





PTHLH
NM_002820
1953
AGTGACTGGGAGTGGGCTAGAA
1954
AAGCCTGTTACCGTGAATCGA





PTK2
NM_005607
1957
GACCGGTCGAATGATAAGGT
1958
CTGGACATCTCGATGACAGC





PTK2B
NM_004103
1961
CAAGCCCAGCCGACCTAAG
1962
GAACCTGGAACTGCAGCTTTG





PTK6
NM_005975
1965
GTGCAGGAAAGGTTCACAAA
1966
GCACACACGATGGAGTAAGG





PTK7
NM_002821
1969
TCAGAGGACTCACGGTTCG
1970
CATACACCTCCACGCTGTTG





PTPN1
NM_002827
1973
AATGAGGAAGTTTCGGATGG
1974
CTTCGATCACAGCCAGGTAG





PTPRK
NM_002844
1977
TCAAACCCTCCCAGTGCT
1978
AGCAGCCAGTTCGTCCAG





PTTG1
NM_004219
1981
GGCTACTCTGATCTATGTTGATAAGG
1982
GCTTCAGCCCATCCTTAGCA





AA







PYCARD
NM_013258
1985
CTTTATAGACCAGCACCGGG
1986
AGCATCCAGCAGCCACTC





RAB27A
NM_004580
1989
TGAGAGATTAATGGGCATTGTG
1990
CCGGATGCTTTATTCGTAGG





RAB30
NM_014488
1993
TAAAGGCTGAGGCACGGA
1994
CTCCCCAGCATCTCATGG





RAB31
NM_006868
1997
CTGAAGGACCCTACGCTCG
1998
ATGCAAAGCCAGTGTGCTC





RAD21
NM_006265
2001
TAGGGATGGTATCTGAAACAACA
2002
TCGCGTACACCTCTGCTC





RAD51
NM_002875
2005
AGACTACTCGGGTCGAGGTG
2006
AGCATCCGCAGAAACCTG





RAD9A
NM_004584
2009
GCCATCTTCACCATCAAGG
2010
CGGTGTCTGAGAGTGTGGC





RAF1
NM_002880
2013
CGTCGTATGCGAGAGTCTGT
2014
TGAAGGCGTGAGGTGTAGAA





RAGE
NM_014226
2017
ATTAGGGGACTTTGGCTCCT
2018
GGGTGGAGATGTATTCCGTG





RALA
NM_005402
2021
TGGTCCTGAATGTAGCGTGT
2022
CCCCATTTCACCTCTTCAAT





RALBP1
NM_006788
2025
GGTGTCAGATATAAATGTGCAAATGC
2026
TTCGATATTGCCAGCAGCTATAAA





RAP1B
NM_
2029
TGACAGCGTGAGAGGTACTAGG
2030
CTGAGCCAAGAACGACTAGCTT



001010942









RARB
NM_000965
2033
ATGAACCCTTGACCCCAAGT
2034
GAGCTGGGTGAGATGCTAGG





RASSF1
NM_007182
2037
AGGGCACGTGAAGTCATTG
2038
AAAGAGTGCAAACTTGCGG





RB1
NM_000321
2041
CGAAGCCCTTACAAGTTTCC
2042
GGACTCTTCAGGGGTGAAAT





RECK
NM_021111
2045
GTCGCCGAGTGTGCTTCT
2046
GTGGGATGATGGGTTTGC





REG4
NM_032044
2049
TGCTAACTCCTGCACAGCC
2050
TGCTAGGTTTCCCCTCTGAA





RELA
NM_021975
2053
CTGCCGGGATGGCTTCTAT
2054
CCAGGTTCTGGAAACTGTGGAT





RFX1
NM_002918
2057
TCCTCTCCAAGTTCGAGCC
2058
CAGGCCCTGGTACAGCAC





RGS10
NM_
2061
AGACATCCACGACAGCGAT
2062
CCATTTGGCTGTGCTCTTG



001005339









RGS7
NM_002924
2065
CAGGCTGCAGAGAGCATTT
2066
TTTGCTTGTGCTTCTGCTTG





RHOA
NM_001664
2069
TGGCATAGCTCTGGGGTG
2070
TGCCACAGCTGCATGAAC





RHOB
NM_004040
2073
AAGCATGAACAGGACTTGACC
2074
CCTCCCCAAGTCAGTTGC





RHOC
NM_175744
2077
CCCGTTCGGTCTGAGGAA
2078
GAGCACTCAAGGTAGCCAAAGG





RLN1
NM_006911
2081
AGCTGAAGGCAGCCCTATC
2082
TTGGAATCCTTTAATGCAGGT





RND3
NM_005168
2085
TCGGAATTGGACTTGGGAG
2086
CTGGTTACTCCCCTCCAACA





RNF114
NM_018683
2089
TGACAGGGGAAGTGGGTC
2090
GGAAGACAGCTTTGGCAAGA





ROBO2
NM_002942
2093
CTACAAGGCCCAGCCAAC
2094
CACCAGTGGCTTTACATTTCAG





RRM1
NM_001033
2097
GGGCTACTGGCAGCTACATT
2098
CTCTCAGCATCGGTACAAGG





RRM2
NM_001034
2101
CAGCGGGATTAAACAGTCCT
2102
ATCTGCGTTGAAGCAGTGAG





S100P
NM_005980
2105
AGACAAGGATGCCGTGGATAA
2106
GAAGTCCACCTGGGCATCTC





SAT1
NM_002970
2109
CCTTTTACCACTGCCTGGTT
2110
ACAATGCTGTGTCCTTCCG





SCUBE2
NM_020974
2113
TGACAATCAGCACACCTGCAT
2114
TGTGACTACAGCCGTGATCCTTA





SDC1
NM_002997
2117
GAAATTGACGAGGGGTGTCT
2118
AGGAGCTAACGGAGAACCTG





SDC2
NM_002998
2121
GGATTGAAGTGGCTGGAAAG
2122
ACCAGCCACAGTACCCTCA





SDHC
NM_003001
2125
CTTCCCTCGGGTCTCAGG
2126
TTCCCTCCTGGTAAAGGTCA





SEC14L1
NM_
2129
AGGGTTCCCATGTGACCAG
2130
GCAGGCATGCTGTGGAAT



001039573









SEC23A
NM_006364
2133
CGTGTGCATTAGATCAGACAGG
2134
CCCATTACCATGTATCCTCCAG





SEMA3A
NM_006080
2137
TTGGAATGCAGTCCGAAGT
2138
CTCTTCATTTCGCCTCTGGA





SEPT9
NM_006640
2141
CAGTGACCACGAGTACCAGG
2142
CTTCGATGGTACCCCACTTG





SERPINA3
NM_001085
2145
GTGTGGCCCTGTCTGCTTA
2146
CCCTGTGCATGTGAGAGCTAC





SERPINB5
NM_002639
2149
CAGATGGCCACTTTGAGAACATT
2150
GGCAGCATTAACCACAAGGATT





SESN3
NM_144665
2153
GACCCTGGTTTTGGGTATGA
2154
GAGCTCGGAATGTTGGCA





SFRP4
NM_003014
2157
TACAGGATGAGGCTGGGC
2158
GTTGTTAGGGCAAGGGGC





SH3RF2
NM_152550
2161
CCATCACAACAGCCTTGAAC
2162
CACTGGGGTGCTGATCTCTA





SH3YL1
NM_015677
2165
CCTCCAAAGCCATTGTCAAG
2166
CTTTGAGAGCCAGAGTTCAGC





SHH
NM_000193
2169
GTCCAAGGCACATATCCACTG
2170
GAAGCAGCCTCCCGATTT





SHMT2
NM_005412
2173
AGCGGGTGCTAGAGCTTGTA
2174
ATGGCACTTCGGTCTCCA





SIM2
NM_005069
2177
GATGGTAGGAAGGGATGTGC
2178
CACAAGGAGCTGTGAATGAGG





SIPA1L1
NM_015556
2181
CTAGGACAGCTTGGCTTCCA
2182
CATAACCGTAGGGCTCCACA





SKIL
NM_005414
2185
AGAGGCTGAATATGCAGGACA
2186
CTATCGGCCTCAGCATGG





SLC22A3
NM_021977
2189
ATCGTCAGCGAGTTTGACCT
2190
CAGGATGGCTTGGGTGAG





SLC25A21
NM_030631
2193
AAGTGTTTTTCCCCCTTGAGAT
2194
GGCCGATCGATAGTCTCTCTT





SLC44A1
NM_080546
2197
AGGACCGTAGCTGCACAGAC
2198
ATCCCATCCCAATGCAGA





SMAD4
NM_005359
2201
GGACATTACTGGCCTGTTCACA
2202
ACCAATACTCAGGAGCAGGATGA





SMARCC2
NM_003075
2205
TACCGACTGAACCCCCAA
2206
GACATCACCCGCTAGGTTTC





SMARCD1
NM_003076
2209
CCGAGTTAGCATATCCCAGG
2210
CCTTTGTGCCCAGCTGTC





SMO
NM_005631
2213
GGCATCCAGTGCCAGAAC
2214
CGCGATGTAGCTGTGCAT





SNAI1
NM_005985
2217
CCCAATCGGAAGCCTAACTA
2218
GTAGGGCTGCTGGAAGGTAA





SNRPB2
NM_003092
2221
CGTTTCCTGCTTTTGGTTCT
2222
AGGTAGAAGGCGCACGAA





SOD1
NM_000454
2225
TGAAGAGAGGCATGTTGGAG
2226
AATAGACACATCGGCCACAC





SORBS1
NM_015385
2229
GCAGATGAGTGGAGGCTTTC
2230
AGCGAGTGAAGAGGGCTG





SOX4
NM_003107
2233
AGATGATCTCGGGAGACTGG
2234
GCGCCCTTCAGTAGGTGA





SPARC
NM_003118
2237
TCTTCCCTGTACACTGGCAGTTC
2238
AGCTCGGTGTGGGAGAGGTA





SPARCL1
NM_004684
2241
GGCACAGTGCAAGTGATGA
2242
GATTGAGCTCTCTCGGCCT





SPDEF
NM_012391
2245
CCATCCGCCAGTATTACAAG
2246
GGGTGCACGAACTGGTAGA





SPINK1
NM_003122
2249
CTGCCATATGACCCTTCCAG
2250
GTTGAAAACTGCACCGCAC





SPINT1
NM_003710
2253
ATTCCCAGCACAGGCTCTGT
2254
AGATGGCTACCACCACCACAA





SPP1
NM_
2257
TCACACATGGAAAGCGAGG
2258
GTTCAGGTCCTGGGCAAC



001040058









SQLE
NM_003129
2261
ATTTTCGAGGCCAAAAAATC
2262
CCTGAGCAAGGATATTCACG





SRC
NM_005417
2265
TGAGGAGTGGTATTTTGGCAAGA
2266
CTCTCGGGTTCTCTGCATTGA





SRD5A1
NM_001047
2269
GGGCTGGAATCTGTCTAGGA
2270
CCATGACTGCACAATGGCT





SRD5A2
NM_000348
2273
GTAGGTCTCCTGGCGTTCTG
2274
TCCCTGGAAGGGTAGGAGTAA





STS
NM_005418
2277
CCTGTCCTGCCAGAGCAT
2278
CAGCTGCACAAAACTGGC





STAT1
NM_007315
2281
GGGCTCAGCTTTCAGAAGTG
2282
ACATGTTCAGCTGGTCCACA





STAT3
NM_003150
2285
TCACATGCCACTTTGGTGTT
2286
CTTGCAGGAAGCGGCTATAC





STAT5A
NM_003152
2289
GAGGCGCTCAACATGAAATTC
2290
GCCAGGAACACGAGGTTCTC





STAT5B
NM_012448
2293
CCAGTGGTGGTGATCGTTCA
2294
GCAAAAGCATTGTCCCAGAGA





STMN1
NM_005563
2297
AATACCCAACGCACAAATGA
2298
GGAGACAATGCAAACCACAC





STS
NM_000351
2301
GAAGATCCCTTTCCTCCTACTGTTC
2302
GGATGATGTTCGGCCTTGAT





SULF1
NM_015170
2305
TGCAGTTGTAGGGAGTCTGG
2306
TCTCAAGAATTGCCGTTGAC





SUMO1
NM_003352
2309
GTGAAGCCACCGTCATCATG
2310
CCTTCCTTCTTATCCCCCAAGT





SVIL
NM_003174
2313
ACTTGCCCAGCACAAGGA
2314
GACACCATCCGTGTCACATC





TAF2
NM_003184
2317
GCGCTCCACTCTCAGTCTTT
2318
CTTGTGCTCATGGTGATGGT





TARP
NM_
2321
GAGCAACACGATTCTGGGA
2322
GGCACCGTTAACCAGCTAAAT



001003799









TBP
NM_003194
2325
GCCCGAAACGCCGAATATA
2326
CGTGGCTCTCTTATCCTCATGAT





TFDP1
NM_007111
2329
TGCGAAGTGCTTTTGTTTGT
2330
GCCTTCCAGACAGTCTCCAT





TFF1
NM_003225
2333
GCCCTCCCAGTGTGCAAAT
2334
CGTCGATGGTATTAGGATAGAAGCA





TFF3
NM_003226
2337
AGGCACTGTTCATCTCAGTTTTTCT
2338
CATCAGGCTCCAGATATGAACTTTC





TGFA
NM_003236
2341
GGTGTGCCACAGACCTTCCT
2342
ACGGAGTTCTTGACAGAGTTTTGA





TGFB1I1
NM_
2345
GCTACTTTGAGCGCTTCTCG
2346
GGTCACCATCTTGTGTCGG



001042454









TGFB2
NM_003238
2349
ACCAGTCCCCCAGAAGACTA
2350
CCTGGTGCTGTTGTAGATGG





TGFB3
NM_003239
2353
GGATCGAGCTCTTCCAGATCCT
2354
GCCACCGATATAGCGCTGTT





TGFBR2
NM_003242
2357
AACACCAATGGGTTCCATCT
2358
CCTCTTCATCAGGCCAAACT





THBS2
NM_003247
2361
CAAGACTGGCTACATCAGAGTCTTAG
2362
CAGCGTAGGTTTGGTCATAGATAGG





TG







THY1
NM_006288
2365
GGACAAGACCCTCTCAGGCT
2366
TTGGAGGCTGTGGGTCAG





TIAM1
NM_003253
2369
GTCCCTGGCTGAAAATGG
2370
GGGCTCCCGAAGTCTTCTA





TIMP2
NM_003255
2373
TCACCCTCTGTGACTTCATCGT
2374
TGTGGTTCAGGCTCTTCTTCTG





TIMP3
NM_000362
2377
CTACCTGCCTTGCTTTGTGA
2378
ACCGAAATTGGAGAGCATGT





TK1
NM_003258
2381
GCCGGGAAGACCGTAATTGT
2382
CAGCGGCACCAGGTTCAG





TMPRSS2
NM_005656
2385
GGACAGTGTGCACCTCAAAG
2386
CTCCCACGAGGAAGGTCC





TMPRSS2
0Q204772
2389
GAGGCGGAGGGCGAG
2390
ACTGGTCCTCACTCACAACT


ERGA










TMPRSS2
0Q204773
2393
GAGGCGGAGGGCGAG
2394
TTCCTCGGGTCTCCAAAGAT


ERGB










TNF
NM_000594
2397
GGAGAAGGGTGACCGACTCA
2398
TGCCCAGACTCGGCAAAG





TNFRSF10A
NM_003844
2401
TGCACAGAGGGTGTGGGTTAC
2402
TCTTCATCTGATTTACAAGCTGTACATG





TNFRSF10B
NM_003842
2405
CTCTGAGACAGTGCTTCGATGACT
2406
CCATGAGGCCCAACTTCCT





TNFRSF18
NM_148901
2409
CAGAAGCTGCCAGTTCCC
2410
CACCCACAGGTCTCCCAG





TNFSF10
NM_003810
2413
CTTCACAGTGCTCCTGCAGTCT
2414
CATCTGCTTCAGCTCGTTGGT





TNFSF11
NM_003701
2417
AACTGCATGTGGGCTATGG
2418
TGACACCCTCTCCACTTCAG





TOP2A
NM_001067
2421
AATCCAAGGGGGAGAGTGAT
2422
GTACAGATTTTGCCCGAGGA





TP53
NM_000546
2425
CTTTGAACCCTTGCTTGCAA
2426
CCCGGGACAAAGCAAATG





TP63
NM_003722
2429
CCCCAAGCAGTGCCTCTACA
2430
GAATCGCACAGCATCAATAACAC





TPD52
NM_005079
2433
GCCTGTGAGATTCCTACCTTTG
2434
ATGTGCTTGGACCTCGCTT





TPM1
NM_
2437
TCTCTGAGCTCTGCATTTGTC
2438
GGCTCTAAGGCAGGATGCTA



001018005









TPM2
NM_213674
2441
AGGAGATGCAGCTGAAGGAG
2442
CCACCTCTTCATATTTGCGG





TPP2
NM_003291
2445
TAACCGTGGCATCTACCTCC
2446
ATGCCAACGCCATGATCT





TPX2
NM_012112
2449
TCAGCTGTGAGCTGCGGATA
2450
ACGGTCCTAGGTTTGAGGTTAAGA





TRA2A
NM_013293
2453
GCAAATCCAGATCCCAACAC
2454
CTTCACGAAGATCCCTCTCTG





TRAF3IP2
NM_147200
2457
CCTCACAGGAACCGAGCA
2458
CTGGGGCTGGGAATCATA





TRAM1
NM_014294
2461
CAAGAAAAGCACCAAGAGCC
2462
ATGTCCGCGTGATTCTGC





TRAP1
NM_016292
2465
TTACCAGTGGCTTTCAGATGG
2466
TGTCCCGGTTCTAACTCCC





TRIM14
NM_033220
2469
CATTCGCCTTAAGGAAAGCA
2470
CAAGGTACCTGGCTTGGTG





TRO
NM_177556
2473
GCAACTGCCACCCATACAG
2474
TGGTGTGGATACTGGCTGTC





TRPC6
NM_004621
2477
CGAGAGCCAGGACTATCTGC
2478
TAGCCGTAGCAAGGCAGC





TRPV6
NM_018646
2481
CCGTAGTCCCTGCAACCTC
2482
TCCTCACTGTTCACACAGGC





TSTA3
NM_003313
2485
CAATTTGGACTTCTGGAGGAA
2486
CACCTCAAAGGCCGAGTG





TUBB2A
NM_001069
2489
CGAGGACGAGGCTTAAAAAC
2490
ACCATGCTTGAGGACAACAG





TYMP
NM_001953
2493
CTATATGCAGCCAGAGATGTGACA
2494
CCACGAGTTTCTTACTGAGAATGG





TYMS
NM_001071
2497
GCCTCGGTGTGCCTTTCA
2498
CGTGATGTGCGCAATCATG





UAP1
NM_003115
2501
CTGGAGACGGTCGTAGCTG
2502
GCCAAGCTTTGTAGAAATAGGG





UBE2C
NM_007019
2505
TGTCTGGCGATAAAGGGATT
2506
ATGGTCCCTACCCATTTGAA





UBE2G1
NM_003342
2509
TGACACTGAACGAGGTGGC
2510
AAGCAGAGAGGAATCGCCT





UBE2T
NM_014176
2513
TGTTCTCAAATTGCCACCAA
2514
AGAGGTCAACACAGTTGCGA





UGDH
NM_003359
2517
GAAACTCCAGAGGGCCAGA
2518
CTCTGGGAACCCAGTGCTC





UGT2B15
NM_001076
2521
AAGCCTGAAGTGGAATGACTG
2522
CCTCCATTTAAAACCCTCCA





UGT2B17
NM_001077
2525
TTGAGTTTGTCATGCGCC
2526
TCCAGGTGAGGTTGTGGG





UHRF1
NM_013282
2529
CTACAGGGGCAAACAGATGG
2530
GGTGTCATTCAGGCGGAC





UTP23
NM_032334
2533
GATTGCACAAAAATGCCAAG
2534
GGAAAGCAGACATTCTGATCC





VCAM1
NM_001078
2537
TGGCTTCAGGAGCTGAATACC
2538
TGCTGTCGTGATGAGAAAATAGTG





VCL
NM_003373
2541
GATACCACAACTCCCATCAAGCT
2542
TCCCTGTTAGGCGCATCAG





VCPIP1
NM_025054
2545
TTTCTCCCAGTACCATTCGTG
2546
TGAATAGGGAGCCTTGGTAGG





VDR
NM_000376
2549
CCTCTCCTTCCAGCCTGAGT
2550
TCATTGCCAAACACTTCGAG





VEGFA
NM_003376
2553
CTGCTGTCTTGGGTGCATTG
2554
GCAGCCTGGGACCACTTG





VEGFB
NM_003377
2557
TGACGATGGCCTGGAGTGT
2558
GGTACCGGATCATGAGGATCTG





VEGFC
NM_005429
2561
CCTCAGCAAGACGTTATTTGAAATT
2562
AAGTGTGATTGGCAAAACTGATTG





VIM
NM_003380
2565
TGCCCTTAAAGGAACCAATGA
2566
GCTTCAACGGCAAAGTTCTCTT





VTI1B
NM_006370
2569
ACGTTATGCACCCCTGTCTT
2570
CCGATGGAGTTTAGCAAGGT





WDR19
NM_025132
2573
GAGTGGCCCAGATGTCCATA
2574
GATGCTTGAGGGCTTGGTT





WFDC1
NM_021197
2577
ACCCCTGCTCTGTCCCTC
2578
ATACCTTCGGCCACGTCAC





WISP1
NM_003882
2581
AGAGGCATCCATGAACTTCACA
2582
CAAACTCCACAGTACTTGGGTTGA





WNT5A
NM_003392
2585
GTATCAGGACCACATGCAGTACATC
2586
TGTCGGAATTGATACTGGCATT





WWOX
NM_016373
2589
ATCGCAGCTGGTGGGTGTAC
2590
AGCTCCCTGTTGCATGGACTT





XIAP
NM_001167
2593
GCAGTTGGAAGACACAGGAAAGT
2594
TGCGTGGCACTATTTTCAAGA





XRCC5
NM_021141
2597
AGCCCACTTCAGCGTCTC
2598
AGCAGGATTCACACTTCCAAC





YY1
NM_003403
2601
ACCCGGGCAACAAGAAGT
2602
GACCGAGAACTCGCCCTC





ZFHX3
NM_006885
2605
CTGTGGAGCCTCTGCCTG
2606
GGAGCAGGGTTGGATTGAG





ZFP36
NM_003407
2609
CATTAACCCACTCCCCTGA
2610
CCCCCACCATCATGAATACT





ZMYND8
NM_183047
2613
GGTCTGGGCCAAACTGAAG
2614
TGCCCGTCTTTATCCCTTAG





ZNF3
NM_017715
2617
CGAAGGGACTCTGCTCCA
2618
GCAGGAGGTCCTCAGAAGG





ZNF827
NM_178835
2621
TGCCTGAGGACCCTCTACC
2622
GAGGTGGCGGAGTGACTTT





ZWINT
NM_007057
2625
TAGAGGCCATCAAAATTGGC
2626
TCCGTTTCCTCTGGGCTT







SEQ

SEQ




Official
ID

ID




Symbol:
NO
Probe Sequence:
NO
Amplicon Sequence:






AAMP
3
CGCTTCAAAGGACCAGACCTCCTC
4
GTGTGGCAGGTGGACACTAAGGAGGAGGTCTGGTCCTTTGAA







GCGGGAGACCTGGAGTGGATGGAG






ABCA5
7
CACATGTGGCGAGCAATTCGAACT
5
GGTATGGATCCCAAAGCCAAACAGCACATGTGGCGAGCAATT







CGAACTGCATTTAAAAACAGAAAGCGGGCTG






ABCB1
11
CAAGCCTGGAACCTATAGCC
12
AAACACCACTGGAGCATTGACTACCAGGCTCGCCAATGATGCT







GCTCAAGTTAAAGGGGCTATAGGTTCCAGGCTTG






ABCC1
15
ACCTGATACGTCTTGGTCTTCATCGCC
16
TCATGGTGCCCGTCAATGCTGTGATGGCGATGAAGACCAAGA





AT

CGTATCAGGTGGCCCACATGAAGAGCAAAGACAATCG






ABCC3
19
TCTGTCCTGGCTGGAGTCGCTTTCAT
20
TCATCCTGGCGATCTACTTCCTCTGGCAGAACCTAGGTCCCTC







TGTCCTGGCTGGAGTCGCTTTCATGGTCTTGCTGATTCCACTC







AACGG






ABCC4
23
CGGAGTCCAGTGTTTTCCCACTTA
24
AGCGCCTGGAATCTACAACTCGGAGTCCAGTGTTTTCCCACTT







ATCATCTTCTCTCCAGGGGCTCT






ABCC8
27
AGTCTCTTGGCCACCTTCAGCCCT
28
CGTCTGTCACTGTGGAGTGGACAGGGCTGAAGGTGGCCAAGA







GACTGCACCGCAGCCTGCTAAACCGGATCA






ABCG2
31
ACGAAGATTTGCCTCCACCTGTGG
32
GGTCTCAACGCCATCCTGGGACCCACAGGTGGAGGCAAATCT







TCGTTATTAGATGTCTTAGCTGCAAGGAAAGATCCAAG






ABHD2
35
CAGGTGGCTCCTTTGATCCCTGA
36
GTAGTGGGTCTGCATGGATGTTTCAGGGATCAAAGGAGCCAC







CTGGGCGCCTGAGTGCCAACCCTCA






ACE
39
TGCCCTCAGCAATGAAGCCTACAA
40
CCGCTGTACGAGGATTTCACTGCCCTCAGCAATGAAGCCTACA







AGCAGGACGGCTTCACAGACACGG






ACOX2
43
TGCTCTCAACTTTCCTGCGGAGTG
44
ATGGAGGTGCCCAGAACACTGCACTCCGCAGGAAAGTTGAGA







GCATCATCCACAGTTACCCGGAGT






ACTR2
47
CCCGCAGAAAGCACATGGTATTCC
48
ATCCGCATTGAAGACCCACCCCGCAGAAAGCACATGGTATTCC







TGGGTGGTGCAGTTCTAGCGGAT






ADAM15
51
TCAGCCACAATCACCAACTCCACA
52
GGCGGGATGTGGTAACAGAGACCAAGACTGTGGAGTTGGTGA







TTGTGGCTGATCACTCGGAGGCCCAGAAAT






ADAMTS1
55
CAAGCCAAAGGCATTGGCTACTTCTTCG
56
GGACAGGTGCAAGCTCATCTGCCAAGCCAAAGGCATTGGCTA







CTTCTTCGTTTTGCAGCCCAAGGTTGTAGAT






ADH5
59
TGTCTGCCCATTATCTTCATTCTGCAA
60
ATGCTGTCATCATTGTCACGGTTTGTCTGCCCATTATCTTCATT







CTGCAAGGGAAAGGGAAAGGAAGCAG






AFAP1
63
CCTCCAGTGCTGTGTTCCCAGAAG
64
GATGTCCATCCTTGAAACAGCCTCTTCTGGGAACACAGCACTG







GAGGTCTCCAGGCATCAGGGTTG






AGTR1
67
ATTGTTCACCCAATGAAGTCCCGC
68
AGCATTGATCGATACCTGGCTATTGTTCACCCAATGAAGTCCC







GCCTTCGACGCACAATGCTTGTAG






AGTR2
71
CCACCCAGACCCCATGTAGCAAAA
72
ACTGGCATAGGAAATGGTATCCAGAATGGAATTTTGCTACATG







GGGTCTGGGTGGGGGCAAAGAGACCCAGTCAAT






AIG1
75
AATCGAGATGAGGACATCGCACCA
76
CGACGGTTCTGCCCTTTATATTAATCGAGATGAGGACATCGCA







CCATCAGTATCCCAGCAGGAGCA






AKAP1
79
CTCCACCAGGGACCGGTTTATCAA
80
TGTGGTTGGAGATGAAGTGGTGTTGATAAACCGGTCCCTGGTG







GAGCGAGGCCTTGCCCAGTGGGTAGAC






AKR1C1
83
CCAAATCCCAGGACAGGCATGAAG
84
GTGTGTGAAGCTGAATGATGGTCACTTCATGCCTGTCCTGGGA







TTTGGCACCTATGCGCCTGCAGAG






AKR1C3
87
TGCGTCACCATCCACACACAGGG
88
GCTTTGCCTGATGTCTACCAGAAGCCCTGTGTGTGGATGGTGA







CGCAGAGGACGTCTCTATGCCGGTGACTGGAC






AKT1
91
CAGCCCTGGACTACCTGCACTCGG
92
CGCTTCTATGGCGCTGAGATTGTGTCAGCCCTGGACTACCTGC







ACTCGGAGAAGAACGTGGTGTACCGGGA






AKT2
95
CAGGTCACGTCCGAGGTCGACACA
96
TCCTGCCACCCTTCAAACCTCAGGTCACGTCCGAGGTCGACA







CAAGGTACTTCGATGATGAATTTACCGCC






AKT3
99
TCACGGTACACAATCTTTCCGGA
100
TTGTCTCTGCCTTGGACTATCTACATTCCGGAAAGATTGTGTAC







CGTGATCTCAAGTTGGAGAATCTAATGCTGG






ALCAM
103
CCAGTTCCTGCCGTCTGCTCTTCT
104
GAGGAATATGGAATCCAAGGGGGCCAGTTCCTGCCGTCTGCT







CTTCTGCCTCTTGATCTCCGCCAC






ALDH18A1
107
CCTGAAACTTGCATCTCCTGCTGC
108
GATGCAGCTGGAACCCAAGCTGCAGCAGGAGATGCAAGTTTC







AGGATGTTCCCCACTGAGCTGGAG






ALDH1A2
111
TCTCTGTAGGGCCCAGCTCTCAGG
112
CACGTCTGTCCCTCTCTGCTTTCTCTGTAGGGCCCAGCTCTCA







GGAATACAAAGTTGAGCCACGGTC






ALKBH3
115
TAAACAGGGCAGTCACTTTCCGCA
116
TCGCTTAGTCTGCACCTCAACCGTGCGGAAAGTGACTGCCCTG







TTTACTGAGGAAAAACTGGGGCTCAGA






ALOX12
119
CATGCTGTTGAGACGCTCGACCTC
120
AGTTCCTCAATGGTGCCAACCCCATGCTGTTGAGACGCTCGAC







CTCTCTGCCCTCCAGGCTAGTGCT






ALOX5
123
CCGCATGCCGTACACGTAGACATC
124
GAGCTGCAGGACTTCGTGAACGATGTCTACGTGTACGGCATG







CGGGGCCGCAAGTCCTCAGGCTTC






AMACR
127
TCCATGTGTTTGATTTCTCCTCAGGC
128
GTCTCTGGGCTGTCAGCTTTCCTTTCTCCATGTGTTTGATTTCT







CCTCAGGCTGGTAGCAAGTTCTGGATCTTATACCCA






AMPD3
131
TACTCTCCCAACATGCGCTGGATC
132
TGGTTCATCCAGCACAAGGTCTACTCTCCCAACATGCGCTGGA







TCATCCAGGTGCCCCGGATTTATG






ANGPT2
135
AAGCTGACACAGCCCTCCCAAGTG
136
CCGTGAAAGCTGCTCTGTAAAAGCTGACACAGCCCTCCCAAGT







GAGCAGGACTGTTCTTCCCACTGCAA






ANLN
139
CCAAAGAACTCGTGTCCCTCGAGC
140
TGAAAGTCCAAAACCAGGAAAATTCCAAAGAACTCGTGTCCCT







CGAGCTGAATCTGGTGATAGCCTTGGTTCTG






ANPEP
143
CTCCCCAACACGCTGAAACCCG
144
CCACCTTGGACCAAAGTAAAGCGTGGAATCGTTACCGCCTCCC







CAACACGCTGAAACCCGATTCCTACCGGGTGACGCTGAGA






ANXA2
147
CCACCACACAGGTACAGCAGCGCT
148
CAAGACACTAAGGGCGACTACCAGAAAGCGCTGCTGTACCTG







TGTGGTGGAGATGACTGAAGCCCGACACG






APC
151
CATTGGCTCCCCGTGACCTGTA
152
GGACAGCAGGAATGTGTTTCTCCATACAGGTCACGGGGAGCC







AATGGTTCAGAAACAAATCGAGTGGGT






APEX1
155
CTTTCGGGAAGCCAGGCCCTT
156
GATGAAGCCTTTCGCAAGTTCCTGAAGGGCCTGGCTTCCCGAA







AGCCCCTTGTGCTGTGTGGAGACCT






APOC1
159
AGGACAGGACCTCCCAACCAAGC
160
CCAGCCTGATAAAGGTCCTGCGGGCAGGACAGGACCTCCCAA







CCAAGCCCTCCAGCAAGGATTCAGAGTG






APOE
163
ACTGGCGCTGCATGTCTTCCAC
164
GCCTCAAGAGCTGGTTCGAGCCCCTGGTGGAAGACATGCAGC







GCCAGTGGGCCGGGCTGGTGGAGAAGGTGCAGG






APRT
167
CCTTAAGCGAGGTCAGCTCCACCA
168
GAGGTCCTGGAGTGCGTGAGCCTGGTGGAGCTGACCTCGCTT







AAGGGCAGGGAGAAGCTGGCACCT






AQP2
171
CTCCTTCCCTTCCCCTTCTCCTGA
172
GTGTGGGTGCCAGTCCTCCTCAGGAGAAGGGGAAGGGAAGG







AGGCCACTTTGAGAGGGCTGAAGGG






AR
175
ACCATGCCGCCAGGGTACCACA
176
CGACTTCACCGCACCTGATGTGTGGTACCCTGGCGGCATGGT







GAGCAGAGTGCCCTATCCCAGTCCCACTTGTGTCA






ARF1
179
CTTGTCCTTGGGTCACCCTGCA
180
CAGTAGAGATCCCCGCAACTCGCTTGTCCTTGGGTCACCCTGC







ATTCCATAGCCATGTGCTTGT






ARHGAP29
183
ATGCCAGACCCAGACAAAGCATCA
184
CACGGTCTCGTGGTGAAGTCAATGCCAGACCCAGACAAAGCA







TCAGCTTGTCCTGGGCAAGCAACTG






ARHGDIB
187
TAAAACCGGGCTTTCACCCAACCT
188
TGGTCCCTAGAACAAGAGGCTTAAAACCGGGCTTTCACCCAAC







CTGCTCCCTCTGATCCTCCATCA






ASAP2
191
CTGGGCTCCAACCAGCTTCAGTCT
192
CGGCCCATCAGCTTCTACCAGCTGGGCTCCAACCAGCTTCAG







TCTAACGCTGTATCTTTGGCCAGAG






ASPN
195
AGTATCACCCAGGGTGCAGCCAC
196
TGGACTAATCTGTGGGAGCAGTTTATTCCAGTATCACCCAGGG







TGCAGCCACACCAGGACTGTGTTGAAGGGTGTTT






ATM
199
CCAGCTGTCTTCGACACTTCTCGC
200
TGCTTTCTACACATGTTCAGGGATTTTTCACCAGCTGTCTTCGA







CACTTCTCGCAAACGAGCCGATCCACAAC






ATP5E
203
TCCAGCCTGTCTCCAGTAGGCCAC
204
CCGCTTTCGCTACAGCATGGTGGCCTACTGGAGACAGGCTGG







ACTCAGCTACATCCGATACTCCCA






ATP5J
207
CTACCCGCCATCGCAATGCATTAT
208
GTCGACCGACTGAAACGGCGGCCCATAATGCATTGCGATGGC







GGGTAGGCGTGTGGGGGCGGAGCCAGGGCCGGAAGTAGAG






ATXN1
211
CGGGCTATGGCTGTCTTCAATCCT
212
GATCGACTCCAGCACCGTAGAGAGGATTGAAGACAGCCATAG







CCCGGGCGTGGCCGTGATACAGTTC






AURKA
215
CTCTGTGGCACCCTGGACTACCTG
216
CATCTTCCAGGAGGACCACTCTCTGTGGCACCCTGGACTACCT







GCCCCCTGAAATGATTGAAGGTCGGA






AURKB
219
TGACGAGCAGCGAACAGCCACG
220
AGCTGCAGAAGAGCTGCACATTTGACGAGCAGCGAACAGCCA







CGATCATGGAGGAGTTGGCAGATGC






AXIN2
223
ACCAGCGCCAACGACAGTGAGATA
224
GGCTATGTCTTTGCACCAGCCACCAGCGCCAACGACAGTGAG







ATATCCAGTGATGCGCTGACGGAT






AZGP1
227
TCTGAGATCCCACATTGCCTCCAA
228
GAGGCCAGCTAGGAAGCAAGGGTTGGAGGCAATGTGGGATCT







CAGACCCAGTAGCTGCCCTTCCTG






BAD
231
TGGGCCCAGAGCATGTTCCAGATC
232
GGGTCAGGGGCCTCGAGATCGGGCTTGGGCCCAGAGCATGTT







CCAGATCCCAGAGTTTGAGCCGAGTGAGCAG






BAG5
235
ACACCGGATTTAGCTCTTGTCGGC
236
ACTCCTGCAATGAACCCTGTTGACACCGGATTTAGCTCTTGTC







GGCCTTCGTGGGGAGCTGTTTGT






BAK1
239
ACACCCCAGACGTCCTGGCCT
240
CCATTCCCACCATTCTACCTGAGGCCAGGACGTCTGGGGTGT







GGGGATTGGTGGGTCTATGTTCCC






BAX
243
TGCCACTCGGAAAAAGACCTCTCGG
244
CCGCCGTGGACACAGACTCCCCCCGAGAGGTCTTTTTCCGAG







TGGCAGCTGACATGTTTTCTGACGGCAA






BBC3
247
CATCATGGGACTCCTGCCCTTACC
248
CCTGGAGGGTCCTGTACAATCTCATCATGGGACTCCTGCCCTT







ACCCAGGGGCCACAGAGCCCCCGAGATGGAGCCCAATTAG






BCL2
251
TTCCACGCCGAAGGACAGCGAT
252
CAGATGGACCTAGTACCCACTGAGATTTCCACGCCGAAGGAC







AGCGATGGGAAAAATGCCCTTAAATCATAGG






BDKRB1
255
ACCTGGCAGCCTCTGATCTGGTGT
256
GTGGCAGAAATCTACCTGGCCAACCTGGCAGCCTCTGATCTG







GTGTTTGTCTTGGGCTTGCCCTTC






BGN
259
CAAGGGTCTCCAGCACCTCTACGC
260
GAGCTCCGCAAGGATGACTTCAAGGGTCTCCAGCACCTCTAC







GCCCTCGTCCTGGTGAACAACAAG






BIK
263
CCGGTTAACTGTGGCCTGTGCCC
264
ATTCCTATGGCTCTGCAATTGTCACCGGTTAACTGTGGCCTGT







GCCCAGGAAGAGCCATTCACTCCTGCC






BIN1
267
CTTCGCCTCCAGATGGCTCCC
268
CCTGCAAAAGGGAACAAGAGCCCTTCGCCTCCAGATGGCTCC







CCTGCCGCCACCCCCGAGATCAGAGTCAACCACG






BIRC5
271
TCTGCCAGACGCTTCCTATCACTCTATTC
272
TTCAGGTGGATGAGGAGACAGAATAGAGTGATAGGAAGCGTC







TGGCAGATACTCCTTTTGCCACTGCTGTGTG






BMP6
275
TGAACCCCGAGTATGTCCCCAAAC
276
GTGCAGACCTTGGTTCACCTTATGAACCCCGAGTATGTCCCCA







AACCGTGCTGTGCGCCAACTAAG






BMPR1B
279
ATTCACATTACCATAGCGGCCCCA
280
ACCACTTTGGCCATCCCTGCATTTGGGGCCGCTATGGTAATGT







GAATGCACTGGGTACAAACACCGC






BRCA1
283
CTATGGGCCCTTCACCAACATGC
284
TCAGGGGGCTAGAAATCTGTTGCTATGGGCCCTTCACCAACAT







GCCCACAGATCAACTGGAATGG






BRCA2
287
CATTCTTCACTGCTTCATAAAGCTCTGCA
288
AGTTCGTGCTTTGCAAGATGGTGCAGAGCTTTATGAAGCAGTG







AAGAATGCAGCAGACCCAGCTTACCTT






BTG1
291
CGCTCGTCTCTTCCTCTCTCCTGC
292
GAGGTCCGAGCGATGTGACCAGGCCGCCATCGCTCGTCTCTT







CCTCTCTCCTGCCGCCTCCTGTCTCGAAAATAACT






BTG3
295
CATGGGTACCTCCTCCTGGAATGC
296
CCATATCGCCCAATTCCAGTGACATGGGTACCTCCTCCTGGAA







TGCATTGTGACCGGAATCACTGG






BTRC
299
CAGTCGGCCCAGGACGGTCTACT
300
GTTGGGACACAGTTGGTCTGCAGTCGGCCCAGGACGGTCTAC







TCAGCACAACTGACTGCTTCA






BUB1
303
TGCTGGGAGCCTACACTTGGCCC
304
CCGAGGTTAATCCAGCACGTATGGGGCCAAGTGTAGGCTCCC







AGCAGGAACTGAGAGCGCCATGTCTT






C7
307
ATGCTCTGCCCTCTGCATCTCAGA
308
ATGTCTGAGTGTGAGGCGGGCGCTCTGAGATGCAGAGGGCAG







AGCATCTCTGTCACCAGCATAAGGCCT






CACNA1D
311
CAGTACACTGGCGTCCATTCCCTG
312
AGGACCCAGCTCCATGTGCGTTCTCAGGGAATGGACGCCAGT







GTACTGCCAATGGCACGGAATGTAGG






CADM1
315
TCTTCACCTGCTCGGGAATCTGTG
316
CCACCACCATCCTTACCATCATCACAGATTCCCGAGCAGGTGA







AGAAGGCTCGATCAGGGCAGTGGATC






CADPS
319
CTCCTGGATGGCCAAATTTGATGC
320
CAGCAAGGAGACTGTGCTGAGCTCCTGGATGGCCAAATTTGAT







GCCATCTACCGTGGAGAAGAGGACC






CASP1
323
TCACAGGCATGACAATGCTGCTACA
324
AACTGGAGCTGAGGTTGACATCACAGGCATGACAATGCTGCTA







CAAAATCTGGGGTACAGCGTAGATG






CASP3
327
TCAGCCTGTTCCATGAAGGCAGAGC
328
TGAGCCTGAGCAGAGACATGACTCAGCCTGTTCCATGAAGGC







AGAGCCATGGACCACGCAGGAAGG






CASP7
331
CTTTCGCTAAAGGGGCCCCAGAC
332
GCAGCGCCGAGACTTTTAGTTTCGCTTTCGCTAAAGGGGCCCC







AGACCCTTGCTGCGGAGCGACGGAGAGAGACT






CAV1
335
ATTTCAGCTGATCAGTGGGCCTCC
336
GTGGCTCAACATTGTGTTCCCATTTCAGCTGATCAGTGGGCCT







CCAAGGAGGGGCTGTAAAATGGAGGCCATTG






CAV2
339
CCCGTACTGTCATGCCTCAGAGCT
340
CTTCCCTGGGACGACTTGCCAGCTCTGAGGCATGACAGTACG







GGCCCCCAGAAGGGTGACCAGGAG






CCL2
343
TGCCCCAGTCACCTGCTGTTA
344
CGCTCAGCCAGATGCAATCAATGCCCCAGTCACCTGCTGTTAT







AACTTCACCAATAGGAAGATCTCAGTGC






CCL5
347
ACAGAGCCCTGGCAAAGCCAAG
348
AGGTTCTGAGCTCTGGCTTTGCCTTGGCTTTGCCAGGGCTCTG







TGACCAGGAAGGAAGTCAGCAT






CCNB1
351
TGTCTCCATTATTGATCGGTTCATGCA
352
TTCAGGTTGTTGCAGGAGACCATGTACATGACTGTCTCCATTAT







TGATCGGTTCATGCAGAATAATTGTGTGCCCAAGAAGATG






CCND1
355
AAGGAGACCATCCCCCTGACGGC
356
GCATGTTCGTGGCCTCTAAGATGAAGGAGACCATCCCCCTGA







CGGCCGAGAAGCTGTGCATCTACACCG






CCNE2
359
TACCAAGCAACCTACATGTCAAGAAAGC
360
ATGCTGTGGCTCCTTCCTAACTGGGGCTTTCTTGACATGTAGG





CC

TTGCTTGGTAATAACCTTTTTGTATATCACAATTTGGGT






CCNH
363
CATCAGCGTCCTGGCGTAAAACAC
364
GAGATCTTCGGTGGGGGTACGGGTGTTTTACGCCAGGACGCT







GATGCGTTTGGGTTCTCGTCTGCAG






CCR1
367
ACTCACCACACCTGCAGCCTTCAC
368
TCCAAGACCCAATGGGAATTCACTCACCACACCTGCAGCCTTC







ACTTTCCTCACGAAAGCCTACGA






CD164
371
CCTCCAATGAAACTGGCTGCATCA
372
CAACCTGTGCGAAAGTCTACCTTTGATGCAGCCAGTTTCATTG







GAGGAATTGTCCTGGTCTTGGGTGT






CD1A
375
CGCACCATTCGGTCATTTGAGG
376
GGAGTGGAAGGAACTGGAAACATTATTCCGTATACGCACCATT







CGGTCATTTGAGGGAATTCGTAGATACGCCCATGA






CD276
379
CCACTGTGCAGCCTTATTTCTCCAATG
380
CCAAAGGATGCGATACACAGACCACTGTGCAGCCTTATTTCTC







CAATGGACATGATTCCCAAGTCATCC






CD44
383
ACTGGAACCCAGAAGCACACCCTC
384
GGCACCACTGCTTATGAAGGAAACTGGAACCCAGAAGCACAC







CCTCCCCTCATTCACCATGAGCATC






CD68
387
CTCCAAGCCCAGATTCAGATTCGAGTCA
388
TGGTTCCCAGCCCTGTGTCCACCTCCAAGCCCAGATTCAGATT







CGAGTCATGTACACAACCCAGGGTGGAGGAG






CD82
391
TCAGCTTCTACAACTGGACAGACAACGC
392
GTGCAGGCTCAGGTGAAGTGCTGCGGCTGGGTCAGCTTCTAC





TG

AACTGGACAGACAACGCTGAGCTCATGAATCGCCCTGAGGTC






CDC20
395
ACTGGCCGTGGCACTGGACAACA
396
TGGATTGGAGTTCTGGGAATGTACTGGCCGTGGCACTGGACA







ACAGTGTGTACCTGTGGAGTGCAAGC






CDC25B
399
CTGCTACCTCCCTTGCCTTTCGAG
400
GCTGCAGGACCAGTGAGGGGCCTGCGCCAGTCCTGCTACCTC







CCTTGCCTTTCGAGGCCTGAAGCCAGCTGCCCTA






CDC6
403
TTGTTCTCCACCAAAGCAAGGCAA
404
GCAACACTCCCCATTTACCTCCTTGTTCTCCACCAAAGCAAGG







CAAGAAAGAGAATGGTCCCCCTCA






CDH1
407
TGCCAATCCCGATGAAATTGGAAATTT
408
TGAGTGTCCCCCGGTATCTTCCCCGCCCTGCCAATCCCGATGA







AATTGGAAATTTTATTGATGAAAATCTGAAAGCGGCTG






CDH10
411
ATGCCGATGACCCTTCATATGGGA
412
TGTGGTGCAAGTCACAGCTACAGATGCCGATGACCCTTCATAT







GGGAACAGCGCCAGAGTCATTTACA






CDH11
415
CCTTCTGCCCATAGTGATCAGCGA
416
GTCGGCAGAAGCAGGACTTGTACCTTCTGCCCATAGTGATCAG







CGATGGCGGCATCCCGCCCATGAGTAG






CDH19
419
ACTCGGAAAACCACAAGCGCTGAG
420
AGTACCATAATGCGGGAACGCAAGACTCGGAAAACCACAAGC







GCTGAGATCAGGAGCCTATACAGGCAGTCT






CDH5
423
TATTCTCCCGGTCCAGCCTCTCAA
424
ACAGGAGACGTGTTCGCCATTGAGAGGCTGGACCGGGAGAAT







ATCTCAGAGTACCACCTCACTGCTG






CDH7
427
ACCTCAACGTCATCCGAGACACCA
428
GTTTGACATGGCTGCACTGAGAAACCTCAACGTCATCCGAGAC







ACCAAGACCCGGAGGGATGTGACT






CDK14
431
CTTCCTGCAGCCTGATCACCTTCA
432
GCAAGGTAAATGGGAAGTTGGTAGCTCTGAAGGTGATCAGGC







TGCAGGAAGAAGAAGGGACACCTTTCACAGCTATC






CDK2
435
CCTTGGCCGAAATCCGCTTGT
436
AATGCTGCACTACGACCCTAACAAGCGGATTTCGGCCAAGGC







AGCCCTGGCTCACCCTTTCTTCCAGGATGTGACCAA






CDK3
439
CTCTGGCTCCAGATTGGGCACAAT
440
CCAGGAAGGGACTGGAAGAGATTGTGCCCAATCTGGAGCCAG







AGGGCAGGGACCTGCTCATGCAAC






CDK7
443
CCTCCCCAAGGAAGTCCAGCTTCT
444
GTCTCGGGCAAAGCGTTATGAGAAGCTGGACTTCCTTGGGGA







GGGACAGTTTGCCACCGTTTACAAGGCCAGAG






CDKN1A
447
CGGCGGCAGACCAGCATGAC
448
TGGAGACTCTCAGGGTCGAAAACGGCGGCAGACCAGCATGAC







AGATTTCTACCACTCCAAACGCC






CDKN1C
451
CGGGCCTCTGATCTCCGATTTCTT
452
CGGCGATCAAGAAGCTGTCCGGGCCTCTGATCTCCGATTTCTT







CGCCAAGCGCAAGAGATCAGCGCCTG






CDKN2B
455
CACAGGATGCTGGCCTTTGCTCTT
456
GACGCTGCAGAGCACCTTTGCACAGGATGCTGGCCTTTGCTCT







TACTACACTGAGGAGAGATTCCCGC






CDKN2C
459
CCTGTAACTTGAGGGCCACCGAAC
460
GAGCACTGGGCAATCGTTACGACCTGTAACTTGAGGGCCACC







GAACTGCTACTCCCGTTCGCCTTTG






CDKN3
463
ATCACCCATCATCATCCAATCGCA
464
TGGATCTCTACCAGCAATGTGGAATTATCACCCATCATCATCC







AATCGCAGATGGAGGGACTCCTGACAT






CDS2
467
CCCGGACATCACATAGGACAGCAG
468
GGGCTTCTTTGCTACTGTGGTGTTTGGCCTTCTGCTGTCCTAT







GTGATGTCCGGGTACAGATGCTTTGTCTGCCCTGT






CENPF
471
ACACTGGACCAGGAGTGCATCCAG
472
CTCCCGTCAACAGCGTTCTTTCCAAACACTGGACCAGGAGTGC







ATCCAGATGAAGGCCAGACTCACCC






CHAF1A
475
TGCACGTACCAGCACATCCTGAAG
476
GAACTCAGTGTATGAGAAGCGGCCTGACTTCAGGATGTGCTG







GTACGTGCACCCGCAGGTGCTACAGAGC






CHN1
479
CCACCATTGGCCGCTTAGTGGTAT
480
TTACGACGCTCGTGAAAGCACATACCACTAAGCGGCCAATGGT







GGTAGACATGTGCATCAGGGAGA






CHRAC1
483
ATCCGGGTCATCATGAAGAGCTCC
484
TCTCGCTGCCTCTATCCCGCATCCGGGTCATCATGAAGAGCTC







CCCCGAGGTGTCCAGCATCAACCAGG






CKS2
487
CTGCGCCCGCTCTTCGCG
488
GGCTGGACGTGGTTTTGTCTGCTGCGCCCGCTCTTCGCGCTCT







CGTTTCATTTTCTGCAGCG






CLDN3
491
CAAGGCCAAGATCACCATCGTGG
492
ACCAACTGCGTGCAGGACGACACGGCCAAGGCCAAGATCACC







ATCGTGGCAGGCGTGCTGTTCCTTCTCGCC






CLTC
495
TCTCACATGCTGTACCCAAAGCCA
496
ACCGTATGGACAGCCACAGCCTGGCTTTGGGTACAGCATGTG







AGATGAAGCGCTGATCCTGTAGTCA






COL11A1
499
CTGCTCGACCTTTGGGTCCTTCAG
500
GCCCAAGAGGGGAAGATGGCCCTGAAGGACCCAAAGGTCGA







GCAGGCCCAACTGGAGACCCAGGTCC






COL1A1
503
TCCTGCGCCTGATGTCCACCG
504
GTGGCCATCCAGCTGACCTTCCTGCGCCTGATGTCCACCGAG







GCCTCCCAGAACATCACCTACCACTG






COL1A2
507
TCTCCTAGCCAGACGTGTTTCTTGTCCT
508
CAGCCAAGAACTGGTATAGGAGCTCCAAGGACAAGAAACACG





TG

TCTGGCTAGGAGAAACTATCAATGCTGGCAGCCAGTTT






COL3A1
511
CTCCTGGTCCCCAAGGTGTCAAAG
512
GGAGGTTCTGGACCTGCTGGTCCTCCTGGTCCCCAAGGTGTC







AAAGGTGAACGTGGCAGTCCTGGT






COL4A1
515
CTCCTTTGACACCAGGGATGCCAT
516
ACAAAGGCCTCCCAGGATTGGATGGCATCCCTGGTGTCAAAG







GAGAAGCAGGTCTTCCTGGGACTC






COL5A1
519
CCAGGGAAACCACGTAATCCTGGA
520
CTCCCTGGGAAAGATGGCCCTCCAGGATTACGTGGTTTCCCTG







GGGACCGAGGGCTTCCTGGTCCAG






COL5A2
523
CCAGGAAATCCTGTAGCACCAGGC
524
GGTCGAGGAACCCAAGGTCCGCCTGGTGCTACAGGATTTCCT







GGTTCTGCGGGCAGAGTTGGACCTCCAGGC






COL6A1
527
CTTCTCTTCCCTGATCACCCTGCG
528
GGAGACCCTGGTGAAGCTGGCCCGCAGGGTGATCAGGGAAG







AGAAGGCCCCGTTGGTGTCCCTGGAGA






COL6A3
531
CCTCTTTGACGGCTCAGCCAATCT
532
GAGAGCAAGCGAGACATTCTGTTCCTCTTTGACGGCTCAGCCA







ATCTTGTGGGCCAGTTCCCTGTT






COL8A1
535
CCTAAGGGAGAGCCAGGAATCCCA
536
TGGTGTTCCAGGGCTTCTCGGACCTAAGGGAGAGCCAGGAAT







CCCAGGGGATCAGGGTTTACAGGG






COL9A2
539
ACACAGGAAATCCGCACTGCCTTC
540
GGGAACCATCCAGGGTCTGGAAGGCAGTGCGGATTTCCTGTG







TCCAACCAACTGTCCACCCGGAAT






CRISP3
543
TGCCAGTTGCCCAGATAACTGTGA
544
TCCCTTATGAACAAGGAGCACCTTGTGCCAGTTGCCCAGATAA







CTGTGACGATGGACTATGCACCAATGGTT






CSF1
547
TCAGATGGAGACCTCGTGCCAAATTACA
548
TGCAGCGGCTGATTGACAGTCAGATGGAGACCTCGTGCCAAA







TTACATTTGAGTTTGTAGACCAGGAACAGTTG






CSK
551
TCCCGATGGTCTGCAGCAGCT
552
CCTGAACATGAAGGAGCTGAAGCTGCTGCAGACCATCGGGAA







GGGGGAGTTCGGAGACGTGATG






CSRP1
555
CCACCCTTCTCCAGGGACCCTTAG
556
ACCCAAGACCCTGCCTCTTCCACTCCACCCTTCTCCAGGGACC







CTTAGATCACATCACTCCACCCCTGC






CTGF
559
AACATCATGTTCTTCTTCATGACCTCGC
560
GAGTTCAAGTGCCCTGACGGCGAGGTCATGAAGAAGAACATG







ATGTTCATCAAGACCTGTGCCTGCCATTACAACT






CTHRC1
563
CAACGCTGACAGCATGCATTTCTG
564
TGGCTCACTTCGGCTAAAATGCAGAAATGCATGCTGTCAGCGT







TGGTATTTCACATTCAATGGAGCTGA






CTNNA1
567
ATGCCTACAGCACCCTGATGTCGCA
568
CGTTCCGATCCTCTATACTGCATCCCAGGCATGCCTACAGCAC







CCTGATGTCGCAGCCTATAAGGCCAACAGGGACCT






CTNNB1
571
AGGCTCAGTGATGTCTTCCCTGTCACCAG
572
GGCTCTTGTGCGTACTGTCCTTCGGGCTGGTGACAGGGAAGA







CATCACTGAGCCTGCCATCTGTGCTCTTCGTCATCTGA






CTNND1
575
TTGATGCCCTCATTTTCATTGTTCAGGC
576
CGGAAACTTCGGGAATGTGATGGTTTAGTTGATGCCCTCATTT







TCATTGTTCAGGCTGAGATTGGGCAGAAGGATTCAG






CTNND2
579
CTATGAAACGAGCCACTACCCGGC
580
GCCCGTCCCTACAGTGAACTGAACTATGAAACGAGCCACTACC







CGGCCTCCCCCGACTCCTGGGTGTGAG






CTSB
583
CCCCGTGGAGGGAGCTTTCTC
584
GGCCGAGATCTACAAAAACGGCCCCGTGGAGGGAGCTTTCTC







TGTGTATTCGGACTTCCTGC






CTSD
587
ACCCTGCCCGCGATCACACTGA
588
GTACATGATCCCCTGTGAGAAGGTGTCCACCCTGCCCGCGAT







CACACTGAAGCTGGGAGGCAAAGGCTACAAGCTGTCCC






CTSK
591
CCCCAGGTGGTTCATAGCCAGTTC
592
AGGCTTCTCTTGGTGTCCATACATATGAACTGGCTATGAACCA







CCTGGGGGACATGACCAGTGAAGAGGTGG






CTSL2
595
CTTGAGGACGCGAACAGTCCACCA
596
TGTCTCACTGAGCGAGCAGAATCTGGTGGACTGTTCGCGTCCT







CAAGGCAATCAGGGCTGCAATGGT






CTSS
599
TGATAACAAGGGCATCGACTCAGACGCT
600
TGACAACGGCTTTCCAGTACATCATTGATAACAAGGGCATCGA







CTCAGACGCTTCCTATCCCTACAAAGCCATGGA






CUL1
603
CAGCCACAAAGCCAGCGTCATTGT
604
ATGCCCTGGTAATGTCTGCATTCAACAATGACGCTGGCTTTGT







GGCTGCTCTTGATAAGGCTTGTGGTCGC






CXCL12
607
TTCTTCGAAAGCCATGTTGCCAGA
608
GAGCTACAGATGCCCATGCCGATTCTTCGAAAGCCATGTTGCC







AGAGCCAACGTCAAGCATCTCAAA






CXCR4
611
CTGAAACTGGAACACAACCACCCACAAG
612
TGACCGCTTCTACCCCAATGACTTGTGGGTGGTTGTGTTCCAG







TTTCAGCACATCATGGTTGGCCTTATCCT






CXCR7
615
CTCAGAGCCAGGGAACTTCTCGGA
616
CGCCTCAGAACGATGGATCTGCATCTCTTCGACTACTCAGAGC







CAGGGAACTTCTCGGACATCAGCTGGCCATGCAAC






CYP3A5
619
TCCCGCCTCAAGTTTCTCACCAAT
620
TCATTGCCCAGTATGGAGATGTATTGGTGAGAAACTTGAGGCG







GGAAGCAGAGAAAGGCAAGCCTGTC






CYR61
623
CAGCACCCTTGGCAGTTTCGAAAT
624
TGCTCATTCTTGAGGAGCATTAAGGTATTTCGAAACTGCCAAG







GGTGCTGGTGCGGATGGACACTAATGCAGCCAC






DAG1
627
CAAGTCAGAGTTTCCCTGGTGCCC
628
GTGACTGGGCTCATGCCTCCAAGTCAGAGTTTCCCTGGTGCC







CCAGAGACAGGAGCACAAGTGGGAT






DAP
631
CTCACCAGCTGGCAGACGTGAACT
632
CCAGCCTTTCTGGTGCTGTTCTCCAGTTCACGTCTGCCAGCTG







GTGAGGGCAGAGGCAGACCTGGTC






DAPK1
635
TCATATCCAAACTCGCCTCCAGCCG
636
CGCTGACATCATGAATGTTCCTCGACCGGCTGGAGGCGAGTTT







GGATATGACAAAGACACATCGTTGCTGAAAGAGA






DARC
639
TCAGCGCCTGTGCTTCCAAGATAA
640
GCCCTCATTAGTCCTTGGCTCTTATCTTGGAAGCACAGGCGCT







GACAGCCGTCCCAGCCCTTCTGTCTG






DDIT4
643
CTAGCCTTTGGGACCGCTTCTCGT
644
CCTGGCGTCTGTCCTCACCATGCCTAGCCTTTGGGACCGCTTC







TCGTCGTCGTCCACCTCCTCTTCG






DDR2
647
AGTGCTCCCTATCCGCTGGATGTC
648
CTATTACCGGATCCAGGGCCGGGCAGTGCTCCCTATCCGCTG







GATGTCTTGGGAGAGTATCTTGCTGGG






DES
651
TGAACCAGGAGTTTCTGACCACGC
652
ACTTCTCACTGGCCGACGCGGTGAACCAGGAGTTTCTGACCA







CGCGCACCAACGAGAAGGTGGAGC






DHRS9
655
ATCAATAATGCTGGTGTTCCCGGC
656
GGAGAAAGGTCTCTGGGGTCTGATCAATAATGCTGGTGTTCCC







GGCGTGCTGGCTCCCACTGACTG






DHX9
659
CCAAGGAACCACACCCACTTGGTT
660
GTTCGAACCATCTCAGCGACAAAACCAAGTGGGTGTGGTTCCT







TGGTCACCTCCACAATCCAACTGGA






DIAPH1
663
TTCTTCTGTCTCCCGCCGCTTC
664
CAAGCAGTCAAGGAGAACCAGAAGCGGCGGGAGACAGAAGA







AAAGATGAGGCGAGCAAAACT






DICER1
667
AGAAAAGCTGTTTGTCTCCCCAGCA
668
TCCAATTCCAGCATCACTGTGGAGAAAAGCTGTTTGTCTCCCC







AGCATACTTTATCGCCTTCACTGCC






DIO2
671
ACTCTTCCACCAGTTTGCGGAAGG
672
CTCCTTTCACGAGCCAGCTGCCAGCCTTCCGCAAACTGGTGG







AAGAGTTCTCCTCAGTGGCTGACTTCCT






DLC1
675
AAAGTCCATTTGCCACTGATGGCA
676
GATTCAGACGAGGATGAGCCTTGTGCCATCAGTGGCAAATGG







ACTTTCCAAAGGGACAGCAAGAGGTG






DLGAP1
679
CGCAGACCACCCATACTACACCCA
680
CTGCTGAGCCCAGTGGAGCACCACCCCGCAGACCACCCATAC







TACACCCAGCGGAACTCCTTCCAGGCT






DLL4
683
CTACCTGGACATCCCTGCTCAGCC
684
CACGGAGGTATAAGGCAGGAGCCTACCTGGACATCCCTGCTC







AGCCCCGCGGCTGGACCTTCCTTCT






DNM3
687
CATATCGCTGACCGAATGGGAACC
688
CTTTCCCACCCGGCTTACAGACATATCGCTGACCGAATGGGAA







CCCCACACCTGCAGAAGGTCCTT






DPP4
691
CGGCTATTCCACACTTGAACACGC
692
GTCCTGGGATCGGGAAGTGGCGTGTTCAAGTGTGGAATAGCC







GTGGCGCCTGTATCCCGGTGGGAGTAC






DPT
695
TTCCTAGGAAGGCTGGCAGACACC
696
CACCTAGAAGCCTGCCCACGATTCCTAGGAAGGCTGGCAGAC







ACCCTGGAACCCTGGGGAGCTACTG






DUSP1
699
CGAGGCCATTGACTTCATAGACTCCA
700
AGACATCAGCTCCTGGTTCAACGAGGCCATTGACTTCATAGAC







TCCATCAAGAATGCTGGAGGAAGGGTGTTTGTC






DUSP6
703
TCTACCCTATGCGCCTGGAAGTCC
704
CATGCAGGGACTGGGATTCGAGGACTTCCAGGCGCATAGGGT







AGAACCAAATGATAGGGTAGGAGCA






DVL1
707
CTTGGAGCAGCCTGCACCTTCTCT
708
TCTGTCCCACCTGCTGCTGCCCCTTGGAGCAGCCTGCACCTTC







TCTCCTCCCATCCGGCAACAGTCTGA






DYNLL1
711
ACCCACGTCAGTGAGTGCTCACAA
712
GCCGCCTACCTCACAGACTTGTGAGCACTCACTGACGTGGGT







AGCGCCCAGGGCCTGCGGGGCGCAGGAGAGCTGGAGTCAGG







C






EBNA1BP2
715
CCCGCTCTCGGATTCGGAGTCG
716
TGCGGCGAGATGGACACTCCCCCGCTCTCGGATTCGGAGTCG







GAATCCGATGAATCCCTTGTCAC






ECE1
719
TCCACTCTCGATACCCTGCACCAG
720
ACCTTGGGATCTGCCTCCAAGCTGGTGCAGGGTATCGAGAGT







GGATTCCAGATGGAGGTCCTGGTCC






EDN1
723
CACTCCCGAGCACGTTGTTCCGT
724
TGCCACCTGGACATCATTTGGGTCAACACTCCCGAGCACGTTG







TTCCGTATGGACTTGGAAGCCCTAGGTCCA






EDNRA
727
CCTTTGCCTCAGGGCATCCTTTT
728
TTTCCTCAAATTTGCCTCAAGATGGAAACCCTTTGCCTCAGGG







CATCCTTTTGGCTGGCACTGGTTGGATGTGTAA






EFNB2
731
CGGACAGCGTCTTCTGCCCTCACT
732
TGACATTATCATCCCGCTAAGGACTGCGGACAGCGTCTTCTGC







CCTCACTACGAGAAGGTCAGCGGGGACTAC






EGF
735
AGAGTTTAACAGCCCTGCTCTGGCTGAC
736
CTTTGCCTTGCTCTGTCACAGTGAAGTCAGCCAGAGCAGGGCT





TT

GTTAAACTCTGTGAAATTTGTCATAAGGGTGTCAGGTATTT






EGR1
739
CGGATCCTTTCCTCACTCGCCCA
740
GTCCCCGCTGCAGATCTCTGACCCGTTCGGATCCTTTCCTCAC







TCGCCCACCATGGACAACTACCCTAAGCTGGAG






EGR3
743
ACCCAGTCTCACCTTCTCCCCACC
744
CCATGTGGATGAATGAGGTGTCTCCTTTCCATACCCAGTCTCA







CCTTCTCCCCACCCTACCTCACCTCTTCTCAGGCA






EIF2C2
747
CGGGTCACATTGCAGACACGGTAC
748
GCACTGTGGGCAGATGAAGAGGAAGTACCGCGTCTGCAATGT







GACCCGGCGGCCCGCCAGTCACCAAACAT






EIF2S3
751
TCTCGTGCTTCAGCCTCCCATGTA
752
CTGCCTCCCTGATTCAAGTGATTCTCGTGCTTCAGCCTCCCAT







GTAGCTGATATTACAGGCACTTGCCACC






EIF3H
755
CAGAACATCAAGGAGTTCACTGCCCA
756
CTCATTGCAGGCCAGATAAACACTTACTGCCAGAACATCAAGG







AGTTCACTGCCCAAAACTTAGGCAAGCTCTTCATGGC






EIF4E
759
ACCACCCCTACTCCTAATCCCCCGACT
760
GATCTAAGATGGCGACTGTCGAACCGGAAACCACCCCTACTC







CTAATCCCCCGACTACAGAAGAGGAGAAAACGGAATCTAA






EIF5
763
CCACTTGCACCCGAATCTTGATCA
764
GAATTGGTCTCCAGCTGCCTTTGATCAAGATTCGGGTGCAAGT







GGAGCAGGAGCCATATACCTGGA






ELK4
767
ATAAACCACCTCAGCCTGGTGCCA
768
GATGTGGAGAATGGAGGGAAAGATAAACCACCTCAGCCTGGT







GCCAAGACCTCTAGCCGCAATGACT






ENPP2
771
TAACTTCCTCTGGCATGGTTGGCC
772
CTCCTGCGCACTAATACCTTCAGGCCAACCATGCCAGAGGAA







GTTACCAGACCCAATTATCCAGGGA






ENY2
775
CTGATCCTTCCAGCCACATTCAATTAAT
776
CCTCAAAGAGTTGCTGAGAGCTAAATTAATTGAATGTGGCTGG





TT

AAGGATCAGTTGAAGGCACACTGTAAAGAGG






EPHA2
779
TGCGCCCGATGAGATCACCG
780
CGCCTGTTCACCAAGATTGACACCATTGCGCCCGATGAGATCA







CCGTCAGCAGCGACTTCGAGGCACGCCAC






EPHA3
783
TATTCCAAATCCGAGCCCGAACAG
784
CAGTAGCCTCAAGCCTGACACTATATACGTATTCCAAATCCGA







GCCCGAACAGCCGCTGGATATGGGACGAA






EPHB2
787
CACCTGATGCATGATGGACACTGC
788
CAACCAGGCAGCTCCATCGGCAGTGTCCATCATGCATCAGGT







GAGCCGCACCGTGGACAGCATTAC






EPHB4
791
CGTCCCATTTGAGCCTGTCAATGT
792
TGAACGGGGTATCCTCCTTAGCCACGGGGCCCGTCCCATTTG







AGCCTGTCAATGTCACCACTGACCGAGAGGTACCT






ERBB2
795
CCAGACCATAGCACACTCGGGCAC
796
CGGTGTGAGAAGTGCAGCAAGCCCTGTGCCCGAGTGTGCTAT







GGTCTGGGCATGGAGCACTTGCGAGAGG






ERBB3
799
CCTCAAAGGTACTCCCTCCTCCCGG
800
CGGTTATGTCATGCCAGATACACACCTCAAAGGTACTCCCTCC







TCCCGGGAAGGCACCCTTTCTTCAGTGGGTCTCAGTTC






ERBB4
803
TGTCCCACGAATAATGCGTAAATTCTCC
804
TGGCTCTTAATCAGTTTCGTTACCTGCCTCTGGAGAATTTACGC





AG

ATTATTCGTGGGACAAAACTTTATGAGGATCGATATGCCTTG






ERCC1
807
CAGCAGGCCCTCAAGGAGCTG
808
GTCCAGGTGGATGTGAAAGATCCCCAGCAGGCCCTCAAGGAG







CTGGCTAAGATGTGTATCCTGGCCG






EREG
811
TAAGCCATGGCTGACCTCTGGAGC
812
TGCTAGGGTAAACGAAGGCATAATAAGCCATGGCTGACCTCTG







GAGCACCAGGTGCCAGGACTTGTCTCCA






ERG
815
AGCCATATGCCTTCTCATCTGGGC
816
CCAACACTAGGCTCCCCACCAGCCATATGCCTTCTCATCTGGG







CACTTACTACTAAAGACCTGGCGGAGG






ESR1
819
CTGGAGATGCTGGACGCCC
820
CGTGGTGCCCCTCTATGACCTGCTGCTGGAGATGCTGGACGC







CCACCGCCTACATGCGCCCACTAGCC






ESR2
823
ATCTGTATGCGGAACCTCAAAAGAGTCC
824
TGGTCCATCGCCAGTTATCACATCTGTATGCGGAACCTCAAAA





CT

GAGTCCCTGGTGTGAAGCAAGATCGCTAGAACA






ETV1
827
ATCGGGAAGGACCCACATACCAAC
828
TCAAACAAGAGCCAGGAATGTATCGGGAAGGACCCACATACC







AACGGCGAGGATCACTTCAGCTCTGGCAGTT






ETV4
831
CAGACAAATCGCCATCAAGTCCCC
832
TCCAGTGCCTATGACCCCCCCAGACAAATCGCCATCAAGTCCC







CTGCCCCTGGTGCCCTTGGACAGT






EZH2
835
TCCTGACTTCTGTGAGCTCATTGCG
836
TGGAAACAGCGAAGGATACAGCCTGTGCACATCCTGACTTCTG







TGAGCTCATTGCGCGGGACTAGGGAGTGTTCGGTG






F2R
839
CCCGGGCTCAACATCACTACCTGT
840
AAGGAGCAAACCATCCAGGTGCCCGGGCTCAACATCACTACC







TGTCATGATGTGCTCAATGAAACCCTGC






FAH
843
TGCCCTTCGTGCACACCAATG
844
GACAGCGTAGTGGTGCATGTGCTGAAGCTGCAGGGTGCCGTG







CCCTTCGTGCACACCAATGTTCCACAGTCCATGTTCAGCT






FABP5
847
CCTGATGCTGAACCAATGCACCAT
848
GCTGATGGCAGAAAAACTCAGACTGTCTGCAACTTTACAGATG







GTGCATTGGTTCAGCATCAGGAGTGGGATGGGAAGGAAAG






FADD
851
AACGCGCTCTTGTCGATTTCCTGT
852
GrITTCGCGAGATAACGGTCGAAAACGCGCTCTTGTCGATTTC







CTGTAGTGAATCAGGCACCGGAG






FAM107A
855
AATTGCCACACTGACCAGCGAAGA
856
AAGTCAGGGAAAACCTGCGGAGAATTGCCACACTGACCAGCG







AAGAGAGAGAGCTGTAGGGCCAGC






FAM13C
859
TCCTGACTTTCTCCGTGGCTCCTC
860
ATCTTCAAAGCGGAGAGCGGGAGGAGCCACGGAGAAAGTCAG







GAGACAGAGCATGTGGTATCCAGC






FAM171B
863
TGAAGATTTTGAAGCTAATACATCCCCC
864
CCAGGAAGGAAAAGCACTGTTGAAGATTTTGAAGCTAATACAT





AC

CCCCCACTAAAAGAAGGGGCAGACCAC






FAM49B
867
TGGCCAGCTCCTCTGTATGACTGC
868
AGATGCAGAAGGCATCTTGGAGGACTTGCAGTCATACAGAGG







AGCTGGCCACGAAATACGAGAGGCAATCCAGC






FAM73A
871
AAGACCTCATGCAGTTACTCATTCGCC
872
TGAGAAGGTGCGCTATTCAAGTACAGAGACTTTAGCTGAAGAC







CTCATGCAGTTACTCATTCGCCGCACTGAGCTTTTAATGGCC






FAP
875
AGCCACTGCAAACATACTCGTTCATCA
876
GTTGGCTCACGTGGGTTACTGATGAACGAGTATGTTTGCAGTG







GCTAAAAAGAGTCCAGAATGTTTCGGTCCTGTC






FAS
879
TCTGGACCCTCCTACCTCTGGTTCTTAC
880
GGATTGCTCAACAACCATGCTGGGCATCTGGACCCTCCTACCT





GT

CTGGTTCTTACGTCTGTTGCTAGATTATCGTCCAAAAGTGTTAA







TGCC






FASLG
883
ACAACATTCTCGGTGCCTGTAACAAAGAA
884
GCACTTTGGGATTCTTTCCATTATGATTCTTTGTTACAGGCACC







GAGAATGTTGTATTCAGTGAGGGTCTTCTTACATGC






FASN
887
TCGCCCACCTACGTACTGGCCTAC
888
GCCTCTTCCTGTTCGACGGCTCGCCCACCTACGTACTGGCCTA







CACCCAGAGCTACCGGGCAAAGC






FCGR3A
891
CCCATGATCTTCAAGCAGGGAAGC
892
GTCTCCAGTGGAAGGGAAAAGCCCATGATCTTCAAGCAGGGA







AGCCCCAGTGAGTAGCTGCATTCCT






FGF10
895
ACACCATGTCCTGACCAAGGGCTT
896
TCTTCCGTCCCTGTCACCTGCCAAGCCCTTGGTCAGGACATGG







TGTCACCAGAGGCCACCAACTCT






FGF17
899
TTCTCGGATCTCCCTCAGTCTGCC
900
GGTGGCTGTCCTCAAAATCTGCTTCTCGGATCTCCCTCAGTCT







GCCCCCAGCCCCCAAACTCCTCCTGGCTAGA






FGF5
903
CCATTGACTTTGCCATCCGGGTAG
904
GCATCGGTTTCCATCTGCAGATCTACCCGGATGGCAAAGTCAA







TGGATCCCACGAAGCCAATATGTT






FGF6
907
CATCCACCTTGCCTCTCAGGCAC
908
GGGCCATTAATTCTGACCACGTGCCTGAGAGGCAAGGTGGAT







GGCCCTGGGACAGAAACTGTTCATCACTATGTCCCGGG






FGF7
911
CAGCCCTGAGCGACACACAAGAAG
912
CCAGAGCAAATGGCTACAAATGTGAACTGTTCCAGCCCTGAGC







GACACACAAGAAGTTATGATTACATGGAAGGAGGGGA






FGFR2
915
TCCCAGAGACCAACGTTCAAGCAGTTG
916
GAGGGACTGTTGGCATGCAGTGCCCTCCCAGAGACCAACGTT







CAAGCAGTTGGTAGAAGACTTGGATCGAATTCTCACTC






FGFR4
919
CCTTTCATGGGGAGAACCGCATT
920
CTGGCTTAAGGATGGACAGGCCTTTCATGGGGAGAACCGCAT







TGGAGGCATTCGGCTGCGCCATCAGCACTGGAGTCTCGT






FKBP5
923
TCTCCCCAGTTCCACAGCAGTGTC
924
CCCACAGTAGAGGGGTCTCATGTCTCCCCAGTTCCACAGCAG







TGTCACAGACGTGAAAGCCAGAACC






FLNA
927
TACCAGGCCCATAGCACTGGACAC
928
GAACCTGCGGTGGACACTTCCGGTGTCCAGTGCTATGGGCCT







GGTATTGAGGGCCAGGGTGTCTTC






FLNC
931
ATGTGCTGTCAGCTACCTGCCCAC
932
CAGGACAATGGTGATGGCTCATGTGCTGTCAGCTACCTGCCCA







CGGAGCCTGGCGAGTACACCATCA






FLT1
935
CTACAGCACCAAGAGCGACGTGTG
936
GGCTCCTGAATCTATCTTTGACAAAATCTACAGCACCAAGAGC







GACGTGTGGTCTTACGGAGTATTGCTGTGGGA






FLT4
939
AGCCCGCTGACCATGGAAGATCT
940
ACCAAGAAGCTGAGGACCTGTGGCTGAGCCCGCTGACCATGG







AAGATCTTGTCTGCTACAGCTTCCAGG






FN1
943
ACTCTCAGGCGGTGTCCACATGAT
944
GGAAGTGACAGACGTGAAGGTCACCATCATGTGGACACCGCC







TGAGAGTGCAGTGACCGGCTACCGTGT






FOS
947
TCCCAGCATCATCCAGGCCCAG
948
CGAGCCCTTTGATGACTTCCTGTTCCCAGCATCATCCAGGCCC







AGTGGCTCTGAGACAGCCCGCTCC






FOXO1
951
TATGAACCGCCTGACCCAAGTGAA
952
GTAAGCACCATGCCCCACACCTCGGGTATGAACCGCCTGACC







CAAGTGAAGACACCTGTACAAGTGCCTCTGCCCC






FOXP3
955
TGTTTCCATGGCTACCCCACAGGT
956
CTGTTTGCTGTCCGGAGGCACCTGTGGGGTAGCCATGGAAAC







AGCACATTCCCAGAGTTCCTCCAC






FOXQ1
959
TGATTTATGTCCCTTCCCTCCCCC
960
TGTTTTTGTCGCAACTTCCATTGATTTATGTCCCTTCCCTCCCC







CCTAAGTACATCAGGGAACCTTTCCA






FSD1
963
CGCACCAAACAAGTGCTGCACA
964
AGGCCTCCTGTCCTTCTACAATGCCCGCACCAAACAAGTGCTG







CACACTTTCAAGACCAGGTTCACACA






FYN
967
CTGAAGCACGACAAGCTGGTCCAG
968
GAAGCGCAGATCATGAAGAAGCTGAAGCACGACAAGCTGGTC







CAGCTCTATGCAGTGGTGTCTGAGGAG






G6PD
971
CCAGCCTCAGTGCCACTTGACATT
972
AATCTGCCTGTGGCCTTGCCCGCCAGCCTCAGTGCCACTTGA







CATTCCTTGTCACCAGCAACATCTCG






GABRG2
975
CTCAGCACCATTGCCCGGAAAT
976
CCACTGTCCTGACAATGACCACCCTCAGCACCATTGCCCGGA







AATCGCTCCCCAAGGTCTCCTATGTCACAGCGATGGATCTC






GADD45A
979
TTCATCTCAATGGAAGGATCCTGCC
980
GTGCTGGTGACGAATCCACATTCATCTCAATGGAAGGATCCTG







CCTTAAGTCAACTTATTTGTTTTTGCCGGG






GADD45B
983
TGGGAGTTCATGGGTACAGA
984
ACCCTCGACAAGACCACACTTTGGGACTTGGGAGCTGGGGCT







GAAGTTGCTCTGTACCCATGAACTCCCA






GDF15
987
TGTTAGCCAAAGACTGCCACTGCA
988
CGCTCCAGACCTATGATGACTTGTTAGCCAAAGACTGCCACTG







CATATGAGCAGTCCTGGTCCTTCCACTGT






GHR
991
CGTGCCTCAGCCTCCTGAGTAGCT
992
CCACCTCCCACAGGTTCAGGCGATTCCCGTGCCTCAGCCTCC







TGAGTAGCTGGGACTACAGGCACGCACC






GNPTAB
995
CCCTGCTCACATGCCTCACATGAT
996
GGATTCACATCGCGGAAAGTCCCTGCTCACATGCCTCACATGA







TTGACCGGATTGTTATGCAAGAAC






GNRH1
999
TCCTGTCCTTCACTGTCCTTGCCA
1000
AAGGGCTAAATCCAGGTGTGACGGTATCTAATGATGTCCTGTC







CTTCACTGTCCTTGCCATCACCAGCCACAGAGATCCAG






GPM6B
1003
CGCTGAGAAACCAAACACACCCAG
1004
ATGTGCTTGGAGTGGCCTGGCTGGGTGTGTTTGGTTTCTCAGC







GGTGCCCGTGTTTATGTTCTACA






GPNMB
1007
CAAACAGTGCCCTGATCTCCGTTG
1008
CAGCCTCGCCTTTAAGGATGGCAAACAGTGCCCTGATCTCCGT







TGGCTGCTTGGCCATATTTGTCA






GPR68
1011
CTCAGCACCGTGGTCATCTTCCTG
1012
CAAGGACCAGATCCAGCGGCTGGTGCTCAGCACCGTGGTCAT







CTTCCTGGCCTGCTTCCTGCCCTACC






GPS1
1015
CCTCCTGCTGGCTTCCTTTGATCA
1016
AGTACAAGCAGGCTGCCAAGTGCCTCCTGCTGGCTTCCTTTGA







TCACTGTGACTTCCCTGAGCTGC






GRB7
1019
CTCCCCACCCTTGAGAAGTGCCT
1020
CCATCTGCATCCATCTTGTTTGGGCTCCCCACCCTTGAGAAGT







GCCTCAGATAATACCCTGGTGGCC






GREM1
1023
TCCACCCTCCCTTTCTCACTCCAC
1024
GTGTGGGCAAGGACAAGCAGGATAGTGGAGTGAGAAAGGGAG







GGTGGAGGGTGAGGCCAAATCAGGTC






GSK3B
1027
CCAGGAGTTGCCACCACTGTTGTC
1028
GACAAGGACGGCAGCAAGGTGACAACAGTGGTGGCAACTCCT







GGGCAGGGTCCAGACAGGCCACAA






GSN
1031
ACCCAGCCAATCGGGATCGGC
1032
CTTCTGCTAAGCGGTACATCGAGACGGACCCAGCCAATCGGG







ATCGGCGGACGCCCATCACCGTGGTGAAGCAAGGCTTTGAGC







C






GSTM1
1035
TCAGCCACTGGCTTCTGTCATAATCAGG
1036
AAGCTATGAGGAAAAGAAGTACACGATGGGGGACGCTCCTGA





AG

TTATGACAGAAGCCAGTGGCTGAATGAAAAATTCAAGCTGGGC







C






GSTM2
1039
CTGAAGCTCTACTCACAGTTTCTGGG
1040
CTGCAGGCACTCCCTGAAATGCTGAAGCTCTACTCACAGTTTC







TGGGGAAGCAGCCATGGTTTCTTGG






HDAC1
1043
TTCTTGCGCTCCATCCGTCCAGA
1044
CAAGTACCACAGCGATGACTACATTAAATTCTTGCGCTCCATC







CGTCCAGATAACATGTCGGAGTACAGCAAGC






HDAC9
1047
CCCCCTGAAGCTCTTCCTCTGCTT
1048
AACCAGGCAGTCACCTTGAGGAAGCAGAGGAAGAGCTTCAGG







GGGACCAGGCGATGCAGGAAGACAGAG






HGD
1051
CTGAGCAGCTCTCAGGATCGGCTT
1052
CTCAGGTCTGCCCCTACAATCTCTATGCTGAGCAGCTCTCAGG







ATCGGCTTTCACTTGTCCACGGAGCACCAATAA






HIP1
1055
CGACTCACTGACCGAGGCCTGTAA
1056
CTCAGAGCCCCACCTGAGCCTGCCGACTCACTGACCGAGGCC







TGTAAGCAGTATGGCAGGGAAACCC






HIRIP3
1059
CCATTGCTCCTGGTTCTGGGTTTC
1060
GGATGAGGAAAAGGGGGATTGGAAACCCAGAACCAGGAGCAA







TGGCCGGAGAAAGTCAGCTAGGGA






HK1
1063
TAAGAGTCCGGGATCCCCAGCCTA
1064
TACGCACAGAGGCAAGCAGCTAAGAGTCCGGGATCCCCAGCC







TACTGCCTCTCCAGCACTTCTCTC






HLA-G
1067
CTGCAAGGACAACCAGGCCAGCAA
1068
CCTGCGCGGCTACTACAACCAGAGCGAGGCCAGTTCTCACAC







CCTCCAGTGGATGATTGGCTGCGACCTG






HLF
1071
TAAGTGATCTGCCCTCCAGGTGGC
1072
CACCCTGCAGGTGTCTGAGACTAAGTGATCTGCCCTCCAGGT







GGCGATCACCTTCTGCTCCTAGGTACC






HNF1B
1075
CCCCTATGAAGACCCAGAAGCGTG
1076
TCCCAGCATCTCAACAAGGGCACCCCTATGAAGACCCAGAAG







CGTGCCGCTCTGTACACCTGGTACG






HPS1
1079
CAGTCACCAGCCCAAAGTGCACTT
1080
GCGGAAGCTGTATGTGCTCAAGTACCTGTTTGAAGTGCACTTT







GGGCTGGTGACTGTGGACGGTCATCTTATCCGAA






HRAS
1083
ACCACCTGCTTCCGGTAGGAATCC
1084
GGACGAATACGACCCCACTATAGAGGATTCCTACCGGAAGCA







GGTGGTCATTGATGGGGAGACGTGC






HSD17B10
1087
TCATGGGCACCTTCAATGTGATCC
1088
CCACCAGACAAGACCGATTCGCTGGCCTCCATTTCTTCAACCC







AGTGCCTGTCATGAAACTTGTGG






HSD17B2
1091
AGTTGCTTCCATCCAACCTGGAGG
1092
GCTTTCCAAGTGGGGAATTAAAGTTGCTTCCATCCAACCTGGA







GGCTTCCTAACAAATATCGCAGGCA






HSD17B3
1095
CTTCATCCTCACAGGGCTGCTGGT
1096
GGGACGTCCTGGAACAGTTCTTCATCCTCACAGGGCTGCTGG







TGTGCCTGGCCTGCCTGGCGAAGTGCGTGAGATTCTCCA






HSD17B4
1099
AGGCGGCGTCCTATTTCCTCAAAT
1100
CGGGAAGCTTCAGAGTACCTTTGTATTTGAGGAAATAGGACGC







CGCCTAAAGGATATTGGGCCTGAGGT






HSD3B2
1103
ACTTCCAGCAGGAAGCCAATCCAG
1104
GCCTTCCTTTAACCCTGATGTACTGGATTGGCTTCCTGCTGGA







AGTAGTGAGCTTCCTACTCAGCCCAATTTACTCC






HSP90AB1
1107
ATCCGCTCCATATTGGCTGTCCAG
1108
GCATTGTGACCAGCACCTACGGCTGGACAGCCAATATGGAGC







GGATCATGAAAGCCCAGGCACTTC






HSPA5
1111
TAATTAGACCTAGGCCTCAGCTGCACTG
1112
GGCTAGTAGAACTGGATCCCAACACCAAACTCTTAATTAGACC





CC

TAGGCCTCAGCTGCACTGCCCGAAAAGCATTTGGGCAGACC






HSPA8
1115
CTCAGGGCCCACCATTGAAGAGGTTG
1116
CCTCCCTCTGGTGGTGCTTCCTCAGGGCCCACCATTGAAGAG







GTTGATTAAGCCAACCAAGTGTAGATGTAGC






HSPB1
1119
CGCACTTTTCTGAGCAGACGTCCA
1120
CCGACTGGAGGAGCATAAAAGCGCAGCCGAGCCCAGCGCCC







CGCACTTTTCTGAGCAGACGTCCAGAGCAGAGTCAGCCAGCA







T






HSPB2
1123
CACCTTTCCCTTCCCCCAAGGAT
1124
CACCACTCCAGAGGTAGCAGCATCCTTGGGGGAAGGGAAAGG







TGCATGGTCCACAATGTATGGTTTGGTCCCA






HSPE1
1127
TCTCCACCCTTTCCTTTAGAACCCG
1128
GCAAGCAACAGTAGTCGCTGTTGGATCGGGTTCTAAAGGAAA







GGGTGGAGAGATTCAACCAGTTAGCGTGAAAGTTGG






HSPG2
1131
CAGCTCCGTGCCTCTAGAGGCCT
1132
GAGTACGTGTGCCGAGTGTTGGGCAGCTCCGTGCCTCTAGAG







GCCTCTGTCCTGGTCACCATTGAG






ICAM1
1135
CCGGCGCCCAACGTGATTCT
1136
GCAGACAGTGACCATCTACAGCTTTCCGGCGCCCAACGTGATT







CTGACGAAGCCAGAGGTCTCAGAAG






IER3
1139
TCAAGTTGCCTCGGAAGTCCCAGT
1140
GTACCTGGTGCGCGAGAGCGTATCCCCAACTGGGACTTCCGA







GGCAACTTGAACTCAGAACACTACAGCGGAGACGC






IFI30
1143
AAAATTCCACCCCATGATCAAGAATCC
1144
ATCCCATGAAGCCCAGATACACAAAATTCCACCCCATGATCAA







GAATCCTGCTCCACTAAGAATGGTGC






IFIT1
1147
AAGTTGCCCCAGGTCACCAGACTC
1148
TGACAACCAAGCAAATGTGAGGAGTCTGGTGACCTGGGGCAA







CTTTGCCTGGATGTATTACCACATGGGCAGACTG






IFNG
1151
TCGACCTCGAAACAGCATCTGACTCC
1152
GCTAAAACAGGGAAGCGAAAAAGGAGTCAGATGCTGTTTCGA







GGTCGAAGAGCATCCCAGTAATGGTTG






IGF1
1155
TGTATTGCGCACCCCTCAAGCCTG
1156
TCCGGAGCTGTGATCTAAGGAGGCTGGAGATGTATTGCGCAC







CCCTCAAGCCTGCCAAGTCAGCTCGCTCTGTCCG






IGF1R
1159
CGCGTCATACCAAAATCTCCGATTTTGA
1160
GCATGGTAGCCGAAGATTTCACAGTCAAAATCGGAGATTTTGG







TATGACGCGAGATATCTATGAGACAGACTATTACCGGAAA






IGF2
1163
TACCCCGTGGGCAAGTTCTTCCAA
1164
CCGTGCTTCCGGACAACTTCCCCAGATACCCCGTGGGCAAGT







TCTTCCAATATGACACCTGGAAGCAGTCCA






IGFBP2
1167
CTTCCGGCCAGCACTGCCTC
1168
GTGGACAGCACCATGAACATGTTGGGCGGGGGAGGCAGTGCT







GGCCGGAAGCCCCTCAAGTCGGGTATGAAGG






IGFBP3
1171
ACACCACAGAAGGCTGTGAGCTCC
1172
ACATCCCAACGCATGCTCCTGGAGCTCACAGCCTTCTGTGGTG







TCATTTCTGAAACAAGGGCGTGG






IGFBP5
1175
CCCGTCAACGTACTCCATGCCTGG
1176
TGGACAAGTACGGGATGAAGCTGCCAGGCATGGAGTACGTTG







ACGGGGACTTTCAGTGCCACACCTTCG






IGKBP6
1179
ATCCAGGCACCTCTACCACGCCCTC
1180
TGAACCGCAGAGACCAACAGAGGAATCCAGGCACCTCTACCA







CGCCCTCCCAGCCCAATTCTGCGGGTGTCCAAGAC






IL10
1183
TTGAGCTGTTTTCCCTGACCTCCC
1184
CTGACCACGCTTTCTAGCTGTTGAGCTGTTTTCCCTGACCTCC







CTCTAATTTATCTTGTCTCTGGGCTTGG






IL11
1187
CCTGTGATCAACAGTACCCGTATGGG
1188
TGGAAGGTTCCACAAGTCACCCTGTGATCAACAGTACCCGTAT







GGGACAAAGCTGCAAGGTCAAGA






IL17A
1191
TGGCTTCTGTCTGATCAAGGCACC
1192
TCAAGCAACACTCCTAGGGCCTGGCTTCTGTCTGATCAAGGCA







CCACACAACCCAGAAAGGAGCTG






IL1A
1195
TCTCCACCCTGGCCCTGTTACAGT
1196
GGTCCTTGGTAGAGGGCTACTTTACTGTAACAGGGCCAGGGT







GGAGAGTTCTCTCCTGAAGCTCCATCC






IL1B
1199
TGCCCACAGACCTTCCAGGAGAAT
1200
AGCTGAGGAAGATGCTGGTTCCCTGCCCACAGACCTTCCAGG







AGAATGACCTGAGCACCTTCTTTCC






IL2
1203
TGCAACTCCTGTCTTGCATTGCAC
1204
ACCTCAACTCCTGCCACAATGTACAGGATGCAACTCCTGTCTT







GCATTGCACTAAGTCTTGCACTTGTCACAAACAGTG






IL6
1207
CCAGATTGGAAGCATCCATCTTTTTCA
1208
CCTGAACCTTCCAAAGATGGCTGAAAAAGATGGATGCTTCCAA







TCTGGATTCAATGAGGAGACTTGCCTGGT






IL6R
1211
CCTTTGGCTTCACGGAAGAGCCTT
1212
CCAGCTTATCTCAGGGGTGTGCGGCCTTTGGCTTCACGGAAG







AGCCTTGCGGAAGGTTCTACGCCAG






IL6ST
1215
CATATTGCCCAGTGGTCACCTCACA
1216
GGCCTAATGTTCCAGATCCTTCAAAGAGTCATATTGCCCAGTG







GTCACCTCACACTCCTCCAAGGCACAATTTT






IL8
1219
TGACTTCCAAGCTGGCCGTGGC
1220
AAGGAACCATCTCACTGTGTGTAAACATGACTTCCAAGCTGGC







CGTGGCTCTCTTGGCAGCCTTCCTGAT






ILF3
1223
ACACAAGACTTCAGCCCGTTGGCT
1224
GACACGCCAAGTGGTTCCAGGCCAGAGCCAACGGGCTGAAGT







CTTGTGTCATTGTGATCCGGGTCTTGAG






ILK
1227
ATGTGCTCCCAGTGCTAGGTGCCT
1228
CTCAGGATTTTCTCGCATCCAAATGTGCTCCCAGTGCTAGGTG







CCTGCCAGTCTCCACCTGCTCCT






IMMT
1231
CAACTGCATGGCTCTGAACAGCCT
1232
CTGCCTATGCCAGACTCAGAGGAATCGAACAGGCTGTTCAGA







GCCATGCAGTTGCTGAAGAGGAAGCCAGAAAAGC






ING5
1235
CCAGCTGCACTTTGTCGTCACTGT
1236
CCTACAGCAAGTGCAAGGAATACAGTGACGACAAAGTGCAGC







TGGCCATGCAGACCTACGAGATG






INHBA
1239
ACGTCCGGGTCCTCACTGTCCTTCC
1240
GTGCCCGAGCCATATAGCAGGCACGTCCGGGTCCTCACTGTC







CTTCCACTCAACAGTCATCAACCACTACCG






INSL4
1243
TGAGAAGACATTCACCACCACCCC
1244
CTGTCATATTGCCCCATGCCTGAGAAGACATTCACCACCACCC







CAGGAGGGTGGCTGCTGGAATCTG






ITGA1
1247
TTGCTGGACAGCCTCGGTACAATC
1248
GCTTCTTCTGGAGATGTGCTCTATATTGCTGGACAGCCTCGGT







ACAATCATACAGGCCAGGTCATTATCTACAGG






ITGA3
1251
CACTCCAGACCTCGCTTAGCATGG
1252
CCATGATCCTCACTCTGCTGGTGGACTATACACTCCAGACCTC







GCTTAGCATGGTAAATCACCGGCTACAAAGCTTC






ITGA4
1255
CGATCCTGCATCTGTAAATCGCCC
1256
CAACGCTTCAGTGATCAATCCCGGGGCGATTTACAGATGCAG







GATCGGAAAGAATCCCGGCCAGAC






ITGA5
1259
TCTGAGCCTTGTCCTCTATCCGGC
1260
AGGCCAGCCCTACATTATCAGAGCAAGAGCCGGATAGAGGAC







AAGGCTCAGATCTTGCTGGACTGTGGAGAAGAC






ITGA6
1263
TCGCCATCTTTTGTGGGATTCCTT
1264
CAGTGACAAACAGCCCTTCCAACCCAAGGAATCCCACAAAAGA







TGGCGATGACGCCCATGAGGCTAAAC






ITGA7
1267
CAGCCAGGACCTGGCCATCCG
1268
GATATGATTGGTCGCTGCTTTGTGCTCAGCCAGGACCTGGCCA







TCCGGGATGAGTTGGATGGTGGGGAATGGAAGTTCT






ITGAD
1271
CAACTGAAAGGCCTGACGTTCACG
1272
GAGCCTGGTGGATCCCATCGTCCAACTGAAAGGCCTGACGTT







CACGGCCACGGGCATCCTGACAGT






ITGB3
1275
AAATACCTGCAACCGTTACTGCCGTGAC
1276
ACCGGGGAGCCCTACATGACGAAAATACCTGCAACCGTTACT







GCCGTGACGAGATTGAGTCAGTGAAAGAGCTTAAGG






ITGB4
1279
CACCAACCTGTACCCGTATTGCGA
1280
CAAGGTGCCCTCAGTGGAGCTCACCAACCTGTACCCGTATTG







CGACTATGAGATGAAGGTGTGCGC






ITGB5
1283
TGCTATGTTTCTACAAAACCGCCAAGG
1284
TCGTGAAAGATGACCAGGAGGCTGTGCTATGTTTCTACAAAAC







CGCCAAGGACTGCGTCATGATGTTCACC






ITPR1
1287
CCATCCTAACGGAACGAGCTCCCT
1288
GAGGAGGTGTGGGTGTTCCGCTTCCATCCTAACGGAACGAGC







TCCCTCTTCGCGGACATGGGATTAC






ITPR3
1291
TCCAGGTCTCGGATCTCAGACACG
1292
TTGCCATCGTGTCAGTGCCCGTGTCTGAGATCCGAGACCTGG







ACTTTGCCAATGACGCCAGCTCCAT






ITSN1
1295
AGCCCTCTCTCACCGTTCCAAGTG
1296
TAACTGGGATGCATGGGCAGCCCAGCCCTCTCTCACCGTTCC







AAGTGCCGGCCAGTTAAGGCAGAG






JAG1
1299
ACTCGATTTCCCAGCCAACCACAG
1300
TGGCTTACACTGGCAATGGTAGTTTCTGTGGTTGGCTGGGAAA







TCGAGTGCCGCATCTCACAGCTATGC






JUN
1303
CTATGACGATGCCCTCAACGCCTC
1304
GACTGCAAAGATGGAAACGACCTTCTATGACGATGCCCTCAAC







GCCTCGTTCCTCCCGTCCGAGAGCGGACCTTATGGCTA






JUNB
1307
CAAGGGACACGCCTTCTGAACGT
1308
CTGTCAGCTGCTGCTTGGGGTCAAGGGACACGCCTTCTGAAC







GTCCCCTGCCCCTTTACGGACACCCCCT






KCNN2
1311
TTATACATTCACATGGACGGCCCG
1312
TGTGCTATTCATCCCATACCTGGGAATTATACATTCACATGGAC







GGCCCGGCTTGCCTTCTCCTATGCCC






KCTD12
1315
ACTCTTAGGCGGCAGCGTCCTTTC
1316
AGCAGTTACTGGCAAGAGGGAGAAAGGACGCTGCCGCCTAAG







AGTGCAAGGCTGCTCAGGTCTCCA






KNDRBS3
1319
CAAGACACAAGGCACCTTCAGCGA
1320
CGGGCAAGAAGAGTGGACTAACTCAAGACACAAGGCACCTTC







AGCGAGGACAGCAAAGGGCGTCTACAG






KIAA0196
1323
TCCCCAGTGTCCAGGCACAGAGTA
1324
CAGACACCAGCTCTGAGGCCAGTTAATCATCCCCAGTGTCCAG







GCACAGAGTAGTCGGTCCGCCTCACAATGTT






KIAA0247
1327
TCCGCTAGTGATCCTTTGCACCCT
1328
CCGTGGGACATGGAGTGTTCCTTCCGCTAGTGATCCTTTGCAC







CCTGCTTGGAGACGGACTTGCTTC






KF4A
1331
CAGGTCAGCAAACTTGAAAGCAGCC
1332
AGAGCTGGTCTCCTCCAAAATACAGGTCAGCAAACTTGAAAGC







AGCCTGAAACAGAGCAAGACCAGC






KIT
1335
TTACAGCGACAGTCATGGCCGCAT
1336
GAGGCAACTGCTTATGGCTTAATTAAGTCAGATGCGGCCATGA







CTGTCGCTGTAAAGATGCTCAAGCCGAGTGCC






KLC1
1339
CAACACGCAGCAGAAACTGCAGAA
1340
AGTGGCTACGGGATGAACTGGCCAACACGCAGCAGAAACTGC







AGAAGAGTGAGCAGTCTGTGGCTCA






KLF6
1343
AGTACTCCTCCAGAGACGGCAGCG
1344
CACGAGACCGGCTACTTCTCGGCGCTGCCGTCTCTGGAGGAG







TACTGGCAACAGACCTGCCTAGAGC






KLK1
1347
TCAGTGAGAGCTTCCCACACCCTG
1348
AACACAGCCCAGTTTGTTCATGTCAGTGAGAGCTTCCCACACC







CTGGCTTCAACATGAGCCTCCTGG






KLK10
1351
CCTCTTCCTCCCCAGTCGGCTGA
1352
GCCCAGAGGCTCCATCGTCCATCCTCTTCCTCCCCAGTCGGCT







GAACTCTCCCCTTGTCTGCACTGTTCAAACCTCTG






KLK11
1355
CCTCCCCAACAAAGACCACCGCA
1356
CACCCCGGCTTCAACAACAGCCTCCCCAACAAAGACCACCGC







AATGACATCATGCTGGTGAAGATG






KLK14
1359
CAGCACTTCAAGTCCTGGCTATAGCCA
1360
CCCCTAAAATGTTCCTCCTGCTGACAGCACTTCAAGTCCTGGC







TATAGCCATGACACAGAGCCAAGAGGATGAG






KLK2
1363
TTGGGAATGCTTCTCACACTCCCA
1364
AGTCTCGGATTGTGGGAGGCTGGGAGTGTGAGAAGCATTCCC







AACCCTGGCAGGTGGCTGTGTACA






KLK3
1367
ACCCACATGGTGACACAGCTCTCC
1368
CCAAGCTTACCACCTGCACCCGGAGAGCTGTGTCACCATGTG







GGTCCCGGTTGTCTTCCTCACCCT






KLRK1
1371
TGTCTCAAAATGCCAGCCTTCTGAA
1372
TGAGAGCCAGGCTTCTTGTATGTCTCAAAATGCCAGCCTTCTG







AAAGTATACAGCAAAGAGGACCAGGAT






KPNA2
1375
ACTCCTGTTTTCACCACCATGCCA
1376
TGATGGTCCAAATGAACGAATTGGCATGGTGGTGAAAACAGGA







GTTGTGCCCCAACTTGTGAAGCTT






KRT1
1379
CCTCAGCAATGATGCTGTCCAGGT
1380
TGGACAACAACCGCAGTCTCGACCTGGACAGCATCATTGCTGA







GGTCAAGGCCCAGTACGAGGATA






KRT15
1383
TGAACAAAGAGGTGGCCTCCAACA
1384
GCCTGGTTCTTCAGCAAGACTGAGGAGCTGAACAAAGAGGTG







GCCTCCAACACAGAAATGATCCAGACCAGCAAG






KRT18
1387
TGGTTCTTCTTCATGAAGAGCAGCTCC
1388
AGAGATCGAGGCTCTCAAGGAGGAGCTGCTCTTCATGAAGAA







GAACCACGAAGAGGAAGTAAAAGGCC






KRT2
1391
ACCTAGACAGCACAGATTCCGCCC
1392
CCAGTGACGCCTCTGTGTTCTGGGGCGGAATCTGTGCTGTCTA







GGTTTGTGCTTCTAGCCATGCCC






KRT5
1395
CCAGTCAACATCTCTGTTGTCACAAGCA
1396
TCAGTGGAGAAGGAGTTGGACCAGTCAACATCTCTGTTGTCAC







AAGCAGTGTTTCCTCTGGATATGGCA






KRT75
1399
TTCATTCTCAGCAGCTGTGCGCTTGT
1400
TCAAAGTCAGGTACGAAGATGAAATTAACAAGCGCACAGCTGC







TGAGAATGAATTTGTAGCCCTGAAAAAGGACGT






KRT76
1403
TCTGGGCTTCAGATCCTGACTCCC
1404
ATCTCCAGACTGCTGGTTCCCAGGGAACCCTCCCTACATCTGG







GCTTCAGATCCTGACTCCCTTCTGTCCCCTAATTCCCTGA






KRT8
1407
CGTCGGTCAGCCCTTCCAGGC
1408
GGATGAAGCTTACATGAACAAGGTAGAGCTGGAGTCTCGCCT







GGAAGGGCTGACCGACGAGATCAACTTCCTCAGGCAGCTATA







TG






L1CAM
1411
ATCTACGTTGTCCAGCTGCCAGCC
1412
CTTGCTGGCCAATGCCTACATCTACGTTGTCCAGCTGCCAGCC







AAGATCCTGACTGCGGACAATCA






LAG3
1415
TCTATCTTGCTCTGAGCCTGCGGA
1416
GCCTTAGAGCAAGGGATTCACCCTCCGCAGGCTCAGAGCAAG







ATAGAGGAGCTGGAGCAAGAACCG






LAMA3
1419
ATTCAGACTGACAGGCCCCTGGAC
1420
CCTGTCACTGAAGCCTTGGAAGTCCAGGGGCCTGTCAGTCTG







AATGGTTGTCCTGACCAGTAACCCA



LAMA4
1423
CTCTCCATCGAGGAAGGCAAATCC
1424
GATGCACTGCGGTTAGCAGCGCTCTCCATCGAGGAAGGCAAA










TCCGGGGTGCTGAGCGTATCCTCTG



LAMA5
1427
CTGTTCCTGGAGCATGGCCTCTTC
1428
CTCCTGGCCAACAGCACTGCACTAGAAGAGGCCATGCTCCAG







GAACAGCAGAGGCTGGGCCTTGTGT






LAMB1
1431
CAAGTGCCTGTACCACACGGAAGG
1432
CAAGGAGACTGGGAGGTGTCTCAAGTGCCTGTACCACACGGA







AGGGGAACACTGTCAGTTCTGCCG






LAMB3
1435
CCACTCGCCATACTGGGTGCAGT
1436
ACTGACCAAGCCTGAGACCTACTGCACCCAGTATGGCGAGTG







GCAGATGAAATGCTGCAAGTGTGAC






LAMC1
1439
CCTCGGTACTTCATTGCTCCTGCA
1440
GCCGTGATCTCAGACAGCTACTTTCCTCGGTACTTCATTGCTC







CTGCAAAGTTCTTGGGCAAGCAGGT






LAMC2
1443
AGGTCTTATCAGCACAGTCTCCGCCTCC
1444
ACTCAAGCGGAAATTGAAGCAGATAGGTCTTATCAGCACAGTC







TCCGCCTCCTGGATTCAGTGTCTCGGCTTCAGGGAGT






LAPTM5
1447
TCCTGACCCTCTGCAGCTCCTACA
1448
TGCTGGACTTCTGCCTGAGCATCCTGACCCTCTGCAGCTCCTA







CATGGAAGTGCCCACCTATCTCA






LGALS3
1451
ACCCAGATAACGCATCATGGAGCGA
1452
AGCGGAAAATGGCAGACAATTTTTCGCTCCATGATGCGTTATC







TGGGTCTGGAAACCCAAACCCTCAAG






LIG3
1455
CTGGACGCTCAGAGCTCGTCTCTG
1456
GGAGGTGGAGAAGGAGCCGGGCCAGAGACGAGCTCTGAGCG







TCCAGGCCTCGCTGATGACACCTGT






LIMS1
1459
ACTGAGCGCACACGAAACACTGCT
1460
TGAACAGTAATGGGGAGCTGTACCATGAGCAGTGTTTCGTGTG







CGCTCAGTGCTTCCAGCAGTTCCCAGAA






LOX
1463
CAGGCTCAGCAAGCTGAACACCTG
1464
CCAATGGGAGAACAACGGGCAGGTGTTCAGCTTGCTGAGCCT







GGGCTCACAGTACCAGCCTCAGCG






LRP1
1467
TCCCGGCTGGGCGCCTCTACT
1468
TTTGGCCCAATGGGCTAAGCCTGGACATCCCGGCTGGGCGCC







TCTACTGGGTGGATGCCTTCTACGACCGCATCGAGAC






LTBP2
1471
CTTTGCAGCCCTCAGAACTCCAGC
1472
GCACACCCATCCTTGAGTCTCCTTTGCAGCCCTCAGAACTCCA







GCCCCACTACGTGGCCAGCCATC






LUM
1475
CCTGACCTTCATCCATCTCCAGCA
1476
GGCTCTTTTGAAGGATTGGTAAACCTGACCTTCATCCATCTCC







AGCACAATCGGCTGAAAGAGGATGCTGTTTCAGCTGCTTTT






MAGEA4
1479
CAGCTTCCCTTGCCTCGTGTAACA
1480
GCATCTAACAGCCCTGTGCAGCAGCTTCCCTTGCCTCGTGTAA







CATGAGGCCCATTCTTCACTCTG






MANF
1483
TTCCTGATGATGCTGGCCCTACAG
1484
CAGATGTGAAGCCTGGAGCTTTCCTGATGATGCTGGCCCTACA







GTACCCCCATGAGGGGATTCCCTT






MAOA
1487
CCGCGATACTCGCCTTCTCTTGAT
1488
GTGTCAGCCAAAGCATGGAGAATCAAGAGAAGGCGAGTATCG







CGGGCCACATGTTCGACGTAGTCG






MAP3K5
1491
CAGCCCAGAGACCAGATGTCTGCT
1492
AGGACCAAGAGGCTACGGAAAAGCAGCAGACATCTGGTCTCT







GGGCTGTACAATCATTGAAATGGCCACAGG






MAP3K7
1495
TGCTGGTCCTTTTCATCCTGGTCC
1496
CAGGCAAGAACTAGTTGCAGAACTGGACCAGGATGAAAAGGA







CCAGCAAAATACATCTCGCCTGGTACAGG






MAP4K4
1499
AACGTTCCTTGTTCTCCTGCTGCA
1500
TCGCCGAGATTTCCTGAGACTGCAGCAGGAGAACAAGGAACG







TTCCGAGGCTCTTCGGAGACAACAG






MAP7
1503
CATGTACAACAAACGCTCCGGGAA
1504
GAGGAACAGAGGTGTCTGCACTTCCATGTACAACAAACGCTCC







GGGAAATGGAAAGCCAGTTGGCAG






MAPKAPK3
1507
ATTGGCACTGCCATCCAGTTTCTG
1508
AAGCTGCAGAGATAATGCGGGATATTGGCACTGCCATCCAGTT







TCTGCACAGCCATAACATTGCCCAC






MCM2
1511
ACAGCTCATTGTTGTCACGCCGGA
1512
GACTTTTGCCCGCTACCTTTCATTCCGGCGTGACAACAATGAG







CTGTTGCTCTTCATACTGAAGCAGTTAGTGGC






MCM3
1515
TGGCCTTTCTGTCTACAAGGATCACCA
1516
GGAGAACAATCCCCTTGAGACAGAATATGGCCTTTCTGTCTAC







AAGGATCACCAGACCATCACCATCCAGGAGAT






MCM6
1519
CAGGTTTCATACCAACACAGGCTTCAGC
1520
TGATGGTCCTATGTGTCACATTCATCACAGGTTTCATACCAACA





AC

CAGGCTTCAGCACTTCCTTTGGTGTGTTTCCTGTCCCA






MDK
1523
ATCACACGCACCCCAGTTCTCAAA
1524
GGAGCCGACTGCAAGTACAAGTTTGAGAACTGGGGTGCGTGT







GATGGGGGCACAGGCACCAAAGTC






MDM2
1527
CTTACACCAGCATCAAGATCCGG
1528
CTACAGGGACGCCATCGAATCCGGATCTTGATGCTGGTGTAAG







TGAACATTCAGGTGATTGGTTGGAT






MELK
1531
CCCGGGTTGTCTTCCGTCAGATAG
1532
AGGATCGCCTGTCAGAAGAGGAGACCCGGGTTGTCTTCCGTC







AGATAGTATCTGCTGTTGCTTATGTGCA






MET
1535
TGCCTCTCTGCCCCACCCTTTGT
1536
GACATTTCCAGTCCTGCAGTCAATGCCTCTCTGCCCCACCCTT







TGTTCAGTGTGGCTGGTGCCACGACAAATGTGTGCGATCGGA







G






MGMT
1539
CAGCCCTTTGGGGAAGCTGG
1540
GTGAAATGAAACGCACCACACTGGACAGCCCTTTGGGGAAGC







TGGAGCTGTCTGGTTGTGAGCAGGGTC






MGST1
1543
TTTGACACCCCTTCCCCAGCCA
1544
ACGGATCTACCACACCATTGCATATTTGACACCCCTTCCCCAG







CCAAATAGAGCTTTGAGTTTTTTTGTTGGATATGGA






MICA
1547
CGAGGCCTCAGAGGGCAACATTAC
1548
ATGGTGAATGTCACCCGCAGCGAGGCCTCAGAGGGCAACATT







ACCGTGACATGCAGGGCTTCTGGCTT






MKI67
1551
CCACTCTTCCTTGAACACCCTCCC
1552
GATTGCACCAGGGCAGAACAGGGGAGGGTGTTCAAGGAAGAG







TGGCTCTTAGCAGAGGCACTTTGGA






MLXIP
1555
CATGAGATGCCAGGAGACCCTTCC
1556
TGCTTAGCTGGCATGTGGCCGCATGAGATGCCAGGAGACCCT







TCCCTGCCCATGGAGAGTAGGCTG






MMP11
1559
ATCCTCCTGAAGCCCTTTTCGCAGC
1560
CCTGGAGGCTGCAACATACCTCAATCCTGTCCCAGGCCGGAT







CCTCCTGAAGCCCTTTTCGCAGCACTGCTATCCTCCAAAGCCA







TTGTA






MMP2
1563
AAGTCCGAATCTCTGCTCCCTGCA
1564
CAGCCAGAAGCGGAAACTTAAAAAGTCCGAATCTCTGCTCCCT







GCAGGGCACAGGTGATGGTGTCT






MMP7
1567
CCTGTATGCTGCAACTCATGAACTTGGC
1568
GGATGGTAGCAGTCTAGGGATTAACTTCCTGTATGCTGCAACT







CATGAACTTGGCCATTCTTTGGGTATGGGACATTCC






MMP9
1571
ACAGGTATTCCTCTGCCAGCTGCC
1572
GAGAACCAATCTCACCGACAGGCAGCTGGCAGAGGAATACCT







GTACCGCTATGGTTACACTCGGGTG






MPPED2
1575
ATTTGACCTTCCAAACCCACAGGG
1576
CCGACCAACCCTCCAATTATATTTGACCTTCCAAACCCACAGG







GTTCCTGAAGCTCTAAATGCCCT






MRC1
1579
CCAACCGCTGTTGAAGCTCAGACT
1580
CTTGACCTCAGGACTCTGGATTGGACTTAACAGTCTGAGCTTC







AACAGCGGTTGGCAGTGGAGTGACCGCAGTCC






MRPL13
1583
CGGCTGGAAATTATGTCCTCCGTC
1584
TCCGGTTCCCTTCGTTTAGGTCGGCTGGAAATTATGTCCTCCG







TCGGTTTTCCGCAGTTTTTCCAC






MSH2
1587
CAAGAAGATTTACTTCGTCGATTCCCAGA
1588
GATGCAGAATTGAGGCAGACTTTACAAGAAGATTTACTTCGTC







GATTCCCAGATCTTAACCGACTTGCCAAGA






MSH3
1591
TCCCAATTGTCGCTTCTTCTGCAG
1592
TGATTACCATCATGGCTCAGATTGGCTCCTATGTTCCTGCAGA







AGAAGCGACAATTGGGATTGTGGATGGCATTTTCACAAG






MSH6
1595
CCGTTACCAGCTGGAAATTCCTGAGA
1596
TCTATTGGGGGATTGGTAGGAACCGTTACCAGCTGGAAATTCC







TGAGAATTTCACCACTCGCAATTTG






MTA1
1599
CCCAGTGTCCGCCAAGGAGCG
1600
CCGCCCTCACCTGCAGAGAAACGCGCTCCTTGGCGGACACTG







GGGGAGGAGAGGAAGAAGCGCGGCTAACTTATTCC






MTPN
1603
AAGCTGCCCACAATCTGCTGCATA
1604
GGTGGAAGGAAACCTCTTCATTATGCAGCAGATTGTGGGCAGC







TTGAAATCCTGGAATTTCTGCTGCTG






MTSS1
1607
CCAAGAAACAGCGACATCAGCCAG
1608
TTCGACAAGTCCTCCACCATTCCAAGAAACAGCGACATCAGCC







AGTCCTACCGACGGATGTTCCAAG






MUC1
1611
CTCTGGCCTTCCGAGAAGGTACC
1612
GGCCAGGATCTGTGGTGGTACAATTGACTCTGGCCTTCCGAG







AAGGTACCATCAATGTCCACGACGTGGAG






MVP
1615
CGCACCTTTCCGGTCTTGACATCCT
1616
ACGAGAACGAGGGCATCTATGTGCAGGATGTCAAGACCGGAA







AGGTGCGCGCTGTGATTGGAAGCACCTACATGC






MYBL2
1619
CAGCATTGTCTGTCCTCCCTGGCA
1620
GCCGAGATCGCCAAGATGTTGCCAGGGAGGACAGACAATGCT







GTGAAGAATCACTGGAACTCTACCATCAAAAG






MYBPC1
1623
AAATTCGCAAGCCCAGCCCCTAT
1624
CAGCAACCAGGGAGTCTGTACCCTGGAAATTCGCAAGCCCAG







CCCCTATGATGGAGGCACTTACTGCTG






MYC
1627
TCTGACACTGTCCAACTTGACCCTCTT
1628
TCCCTCCACTCGGAAGGACTATCCTGCTGCCAAGAGGGTCAA







GTTGGACAGTGTCAGAGTCCTGAGACAGATCAGCAACAACCG






MYLK3
1631
CACACCCTCACAGATCTGCCTGGT
1632
CACCTGACTGAGCTGGATGTGGTCCTGTTCACCAGGCAGATCT







GTGAGGGTGTGCATTACCTGCACCAGCACTACATC






MYO6
1635
CAATCCTCAGGGCCAGCTCCC
1636
AAGCAGTTCTGGAGCAGGAGCGCAGGGACCGGGAGCTGGCC







CTGAGGATTGCCCAGAGTGAAGCCGAGCTCATC






NCAM1
1639
CTCAGCCTCGTCGTTCTTATCCACC
1640
TAGTTCCCAGCTGACCATCAAAAAGGTGGATAAGAACGACGAG







GCTGAGTACATCTGCATTGCTGAGAACAAGGCTG






NCAPD3
1643
CTACTGTCCGCAGCAAGGCACTGT
1644
TCGTTGCTTAGACAAGGCGCCTACTGTCCGCAGCAAGGCACT







GTCCAGCTTTGCACACTGTCTGGAG






NCOR1
1647
CCAGGCTCAGTCTGTCCATCATCA
1648
AACCGTTACAGCCCAGAATCCCAGGCTCAGTCTGTCCATCATC







AAAGACCAGGTTCAAGGGTCTCTCCAGA






NCOR2
1651
CCTCATAGGACAAGACGTGGCCCT
1652
CGTCATCTACGAAGGCAAGAAGGGCCACGTCTTGTCCTATGA







GGGTGGCATGTCTGTGACCCAGTGCTC






NDRG1
1655
CTGCAAGGACACTCATCACAGCCA
1656
AGGGCAACATTCCACAGCTGCCCTGGCTGTGATGAGTGTCCTT







GCAGGGGCCGGAGTAGGAGCACTG






NDUFS5
1659
TGTCCAAGAAAGGCATGGCTACCC
1660
AGAAGAGTCAAGGGCACGAGCATCGGGTAGCCATGCCTTTCT







TGGACATCCAGAAAAGGTTCGGCCT






NEK2
1663
TGCCTTCCCGGGCTGAGGACT
1664
GTGAGGCAGCGCGACTCTGGCGACTGGCCGGCCATGCCTTCC







CGGGCTGAGGACTATGAAGTGTTGTACACCATTGGCA






NETO2
1667
AGCCAACCCTTTTCTCCCATCACA
1668
CCAGGGCACCATACTGTTTCCAGCAGCCAACCCTTTTCTCCCA







TCACAACTACGAAGACCTTGATTTACCGTT






NEXN
1671
TCATCTTCAGCAGTGGAGCCATTCA
1672
AGGAGGAGGAAGAAGGTAGCATCATGAATGGCTCCACTGCTG







AAGATGAAGAGCAAACCAGATCAGGAGCTC






NFAT5
1675
CGAGAATCAGTCCCCGTGGAGTTC
1676
CTGAACCCCTCTCCTGGTCACCGAGAATCAGTCCCCGTGGAG







TTCCCCCTCCACCTCGCCATCGTTTCCT






NFATC2
1679
CGGGTTCCTACCCCACAGTCATTC
1680
CAGTCAAGGTCAGAGGCTGAGCCCGGGTTCCTACCCCACAGT







CATTCAGCAGCAGAATGCCACGAGCCAAAG






NFKB1
1683
AAGCTGTAAACATGAGCCGCACCA
1684
CAGACCAAGGAGATGGACCTCAGCGTGGTGCGGCTCATGTTT







ACAGCTTTTCTTCCGGATAGCACTGGCAGCT






NFKBIA
1687
CTCGTCTTTCATGGAGTCCAGGCC
1688
CTACTGGACGACCGCCACGACAGCGGCCTGGACTCCATGAAA







GACGAGGAGTACGAGCAGATGGTCAAGG






NME1
1691
CCTGGGACCATCCGTGGAGACTTCT
1692
CCAACCCTGCAGACTCCAAGCCTGGGACCATCCGTGGAGACT







TCTGCATACAAGTTGGCAGGAACATTATACAT






NNMT
1695
CCCTCTCCTCATGCCCAGACTCTC
1696
CCTAGGGCAGGGATGGAGAGAGAGTCTGGGCATGAGGAGAG







GGTCTCGGGATGTTTGGCTGGACTAG






NOS3
1699
TTCACTCGCTTCGCCATCACCG
1700
ATCTCCGCCTCGCTCATGGGCACGGTGATGGCGAAGCGAGTG







AAGGCGACAATCCTGTATGGCTCCGA






NOX4
1703
CCGAACACTCTTGGCTTACCTCCG
1704
CCTCAACTGCAGCCTTATCCTTTTACCCATGTGCCGAACACTC







TTGGCTTACCTCCGAGGATCACAGAAGGTTCCAAGCA






NPBWR1
1707
ATCGCCGACGAGCTCTTCACG
1708
TCACCAACCTGTTCATCCTCAACCTGGCCATCGCCGACGAGCT







CTTCACGCTGGTGCTGCCCATCAACATC






NPM1
1711
AACAGGCATTTTGGACAACACATTCTTG
1712
AATGTTGTCCAGGTTCTATTGCCAAGAATGTGTTGTCCAAAATG







CCTGTTTAGTTTTTAAAGATGGAACTCCACCCTTTGCTTG






NRG1
1715
ATGACCACCCCGGCTCGTATGTCA
1716
CGAGACTCTCCTCATAGTGAAAGGTATGTGTCAGCCATGACCA







CCCCGGCTCGTATGTCACCTGTAGATTTCCACACGCCAAG






NRIP3
1719
AGCTTTCTCTACCCCGGCATCTCA
1720
CCCACAAGCATGAAGGAGAAAAGCTTTCTCTACCCCGGCATCT







CAAAGTAGTGGGCCAGATTGAGCA






NRP1
1723
CAGGATCTACCCCGAGAGAGCCACTCAT
1724
CAGCTCTCTCCACGCGATTCATCAGGATCTACCCCGAGAGAG







CCACTCATGGCGGACTGGGGCTCAGAATGGAGCTGCTGGG






NUP62
1727
TCATCTGCCACCACTGGACTCTCC
1728
AGCCTCTTTGCGTCAATAGCAACTGCTCCAACCTCATCTGCCA







CCACTGGACTCTCCCTCTGTACCCCTGTGACCACAG






OAZ1
1731
CTGCTCCTCAGCGAACTCCAGGAG
1732
AGCAAGGACAGCTTTGCAGTTCTCCTGGAGTTCGCTGAGGAG







CAGCTGCGAGCCGACCATGTCTTC






OCLN
1735
CTCCTCCCTCGGTGACCAATTCAC
1736
CCCTCCCATCCGAGTTTCAGGTGAATTGGTCACCGAGGGAGG







AGGCCGACACACCACACCTACACTCCCGCGTC






ODC1
1739
CCAGCGTTGGACAAATACTTTCCGTCA
1740
AGAGATCACCGGCGTAATCAACCCAGCGTTGGACAAATACTTT







CCGTCAGACTCTGGAGTGAGAATCATAGCTGAGCCCG






OLFML2B
1743
TGGCCTGGATCTCCTGAAGCTACA
1744
CATGTTGGAAGGAGCGTTCTATGGCCTGGATCTCCTGAAGCTA







CATTCAGTCACCACCAAACTGGTG






OLFML3
1747
CAGACGATCCACTCTCCCGGAGAT
1748
TCAGAACTGAGGCCGACACCATCTCCGGGAGAGTGGATCGTC







TGGAGCGGGAGGTAGACTATCTGG






OMD
1751
TCCGATGCACATTCAGCAACTCTACC
1752
CGCAAACTCAAGACTATCCCAAATATTCCGATGCACATTCAGC







AACTCTACCTTCAGTTCAATGAAATTGAGGCTGTGACTG






OR51E1
1755
TCCTCATCTCCACCTCATCCATGC
1756
GCATGCTTTCAGGCATTGACATCCTCATCTCCACCTCATCCAT







GCCCAAAATGCTGGCCATCTTCT






OR51E2
1759
ACATAGCCAGCACCCGTGTTCTGA
1760
TATGGTGCCAAAACCAAACAGATCAGAACACGGGTGCTGGCT







ATGTTCAAGATCAGCTGTGACAAGGAC






OSM
1763
CTGAGCTGGCCTCCTATGCCTCAT
1764
GTTTCTGAAGGGGAGGTCACAGCCTGAGCTGGCCTCCTATGC







CTCATCATGTCCCAAACCAGACACCT






PAGE1
1767
CCAACTCAAAGTCAGGATTCTACACCTGC
1768
CAACCTGACGAAGTGGAATCACCAACTCAAAGTCAGGATTCTA







CACCTGCTGAAGAGAGAGAGGATGAGGGAGCATCTG






PAGE4
1771
CCAACTGACAATCAGGATATTGAACCTGG
1772
GAATCTCAGCAAGAGGAACCACCAACTGACAATCAGGATATTG







AACCTGGACAAGAGAGAGAAGGAACACCTCCGATCGAAGAAC






PAK6
1775
AGTTTCAGGAAGGCTGCCCCTCTC
1776
CCTCCAGGTCACCCACAGCCAGTTTCAGGAAGGCTGCCCCTC







TCTCCCACTAAGTTCTGGCCTGAAGGGAC






PATE1
1779
CAGCACAGTTCTTTAGGCAGCCCA
1780
TGGTAATCCCTGGTTAACCTTCATGGGCTGCCTAAAGAACTGT







GCTGATGTGAAAGGCATAAGGTGGA






PCA3
1783
CTGAGATGCTCCCTGCCTTCAGTG
1784
CGTGATTGTCAGGAGCAAGACCTGAGATGCTCCCTGCCTTCAG







TGTCCTCTGCATCTCCCCTTTCT






PCDHGB7
1787
ATTCTTAAACAGCAAGCCCCGCC
1788
CCCAGCGTTGAAGCAGATAAGAAGATTCTTAAACAGCAAGCCC







CGCCCAACACGGACTGGCGTTTC






PCNA
1791
ATCCCAGCAGGCCTCGTTGATGAG
1792
GAAGGTGTTGGAGGCACTCAAGGACCTCATCAACGAGGCCTG







CTGGGATATTAGCTCCAGCGGTGTAAACC






PDE9A
1795
TACATCATCTGGGCCACGCAGAAG
1796
TTCCACAACTTCCGGCACTGCTTCTGCGTGGCCCAGATGATGT







ACAGCATGGTCTGGCTCTGCAGTCT






PDGFRB
1799
ATCAATGTCCCTGTCCGAGTGCTG
1800
CCAGCTCTCCTTCCAGCTACAGATCAATGTCCCTGTCCGAGTG







CTGGAGCTAAGTGAGAGCCACCC






PECAM1
1803
TTTATGAACCTGCCCTGCTCCCACA
1804
TGTATTTCAAGACCTCTGTGCACTTATTTATGAACCTGCCCTGC







TCCCACAGAACACAGCAATTCCTCAGGCTAA






PEX10
1807
CTACCTTCGGCACTACCGCTGAGC
1808
GGAGAAGTTCCCTCCCCAGAAGCTCATCTACCTTCGGCACTAC







CGCTGAGCCGGCGCCCGGGTGGGCCTGGACACAGAT






PGD
1811
ACTGCCCTCTCCTTCTATGACGGGT
1812
ATTCCCATGCCCTGTTTTACCACTGCCCTCTCCTTCTATGACGG







GTACAGACATGAGATGCTTCCAGCCAG






PGF
1815
ATCTTCTCAGACGTCCCGAGCCAG
1816
GTGGTTTTCCCTCGGAGCCCCCTGGCTCGGGACGTCTGAGAA







GATGCCGGTCATGAGGCTGTTCCCTTGCT






PGK1
1819
TCTCTGCTGGGCAAGGATGTTCTGTTC
1820
AGAGCCAGTTGCTGTAGAACTCAAATCTCTGCTGGGCAAGGAT







GTTCTGTTCTTGAAGGACTGTGTAGGCCCAG






PGR
1823
TAAATTGCCGTCGCAGCCGCA
1824
GATAAAGGAGCCGCGTGTCACTAAATTGCCGTCGCAGCCGCA







GCCACTCAAGTGCCGGACTTGTGA






PHTF2
1827
ACAATCTGGCAATGCACAGTTCCC
1828
GATATGGCTGATGCTGCTCCTGGGAACTGTGCATTGCCAGATT







GTTTCCACAAGAACACCCAAACC






PIK3C2A
1831
TGTGCTGTGACTGGACTTAACAAATAGC
1832
ATACCAATCACCGCACAAACCCAGGCTATTTGTTAAGTCCAGT





CT

CACAGCACAAAGAAACATATGCGGAGAAAATGCTAGTGTG






PIK3CA
1835
TCCTGCTTCTCGGGATACAGACCA
1836
GTGATTGAAGAGCATGCCAATTGGTCTGTATCCCGAGAAGCAG







GATTTAGCTATTCCCACGCAGGAC






PIK3CG
1839
TTCTGGACAATTACTGCCACCCGA
1840
GGAGAACTCAATGTCCATCTCCATTCTTCTGGACAATTACTGC







CACCCGATAGCCCTGCCTAAGCATCA






PIM1
1843
TACACTCGGGTCCCATCGAAGTCC
1844
CTGCTCAAGGACACCGTCTACACGGACTTCGATGGGACCCGA







GTGTATAGCCCTCCAGAGTGGATCC






PLA2G7
1847
TGGCAATACATAAATCCTGTTGCCCA
1848
CCTGGCTGTGGTTTATCCTTTTGACTGGCAATACATAAATCCTG







TTGCCCATATGAAATCATCAGCATGGGTCA






PLAU
1851
AAGCCAGGCGTCTACACGAGAGTCTCAC
1852
GTGGATGTGCCCTGAAGGACAAGCCAGGCGTCTACACGAGAG







TCTCACACTTCTTACCCTGGATCCGCAG






PLAUR
1855
CATTGACTGCCGAGGCCCCATG
1856
CCCATGGATGCTCCTCTGAAGAGACTTTCCTCATTGACTGCCG







AGGCCCCATGAATCAATGTCTGGTAGCCACCGG






PLG
1859
TGCCAGGCCTGGGACTCTCA
1860
GGCAAAATTTCCAAGACCATGTCTGGACTGGAATGCCAGGCCT







GGGACTCTCAGAGCCCACACGCTCATGGATACAT






PLK1
1863
AACCCCGTGGCCGCCTCC
1864
AATGAATACAGTATTCCCAAGCACATCAACCCCGTGGCCGCCT







CCCTCATCCAGAAGATGCTTCAGACA






PLOD2
1867
TCCAGCCTTTTCGTGGTGACTCAA
1868
CAGGGAGGTGGTTGCAAATTTCTAAGGTACAATTGCTCTATTG







AGTCACCACGAAAAGGCTGGAGCTTCATGCATCCTGGGAGA






PLP2
1871
ACACCAGGCTACTCCTCCCTGTCG
1872
CCTGATCTGCTTCAGTGCCTCCACACCAGGCTACTCCTCCCTG







TCGGTGATTGAGATGATCCTTGCTGC






PNLIPRP2
1875
ACCCGTGCCTCCAGTCCACAC
1876
TGGAGAAGGTGAACTGCATCTGTGTGGACTGGAGGCACGGGT







CCCGGGCAATGTACACCCAAGCCGTG






POSTN
1879
TTCTCCATCTGGCCTCAGAGCAGA
1880
GTGGCCCAATTAGGCTTGGCATCTGCTCTGAGGCCAGATGGA







GAATACACTTTGCTGGCACCTGTGA






PPAP2B
1883
ACCAGGGCTCCTTGAGCAAATCCT
1884
ACAAGCACCATCCCAGTGATGTTCTGGCAGGATTTGCTCAAGG







AGCCCTGGTGGCCTGCTGCATAGTTTTCTTCGTG






PPFIA3
1887
CACCCACTTTACCTTCTGGTGCCC
1888
CCTGGAGCTCCGTTACTCTCAGGCACCCACTTTACCTTCTGGT







GCCCACCTGGATCCCTATGTGGCT






PPP1R12A
1891
CCGTTCTTCTTCCTTTCGAGCTGC
1892
CGGCAAGGGGTTGATATAGAAGCAGCTCGAAAGGAAGAAGAA







CGGATCATGCTTAGAGATGCCAGGCA






PPP3CA
1895
TACATGCGGTACCCTGCATCTTGG
1896
ATACTCCGAGCCCACGAAGCCCAAGATGCAGGGTACCGCATG







TACAGGAAAAGCCAAACAACAGGCTTCC






PRIMA1
1899
TGACGCATCCAGGGCTCTAGTCTG
1900
ATCCTCTTCCCTGAGCCGCTGACGCATCCAGGGCTCTAGTCTG







CACATAAATTCCCTCTCAGCTGGG






PRKAR1B
1903
AAGGCCATCTCCAAGAACGTGCTC
1904
ACAAAACCATGACTGCGCTGGCCAAGGCCATCTCCAAGAACG







TGCTCTTCGCTCACCTGGATGACA






PRKAR2B
1907
CGAACTGGCCTTAATGTACAATACACCCA
1908
TGATAATCGTGGGAGTTTCGGCGAACTGGCCTTAATGTACAAT







ACACCCAGAGCAGCTACAATCACTGCTACCTCTCCTGGTGC






PRKCA
1911
CAGCCTCTGCGGAATGGATCACACT
1912
CAAGCAATGCGTCATCAATGTCCCCAGCCTCTGCGGAATGGAT







CACACTGAGAAGAGGGGGCGGATTTAC






PRKCB
1915
CCAGACCATGGACCGCCTGTACTT
1916
GACCCAGCTCCACTCCTGCTTCCAGACCATGGACCGCCTGTA







CTTTGTGATGGAGTACGTGAATGGG






PROM1
1919
ACCCGAGGCTGTGTCTCCAACAC
1920
CTATGACAGGCATGCCACCCCGACCACCCGAGGCTGTGTCTC







CAACACCGGAGGCGTCTTCCTCATGGTTGGAG






PROS1
1923
CTCATCCTGACAGACTGCAGCTGC
1924
GCAGCACAGGAATCTTCTTCTTGGCAGCTGCAGTCTGTCAGGA







TGAGATATCAGATTAGGTTGGATAGGTGGG






PSCA
1927
CCTGTGAGTCATCCACGCAGTTCA
1928
ACCGTCATCAGCAAAGGCTGCAGCTTGAACTGCGTGGATGAC







TCACAGGACTACTACGTGGGCAAGAAGAACATCACG






PSMD13
1931
CCTGAAGTGTCAGCTGATGCCACA
1932
GGAGGAGCTCTACACGAAGAAGTTGTGGCATCAGCTGACACT







TCAGGTGCTTGATTTTGTGCAGGATCCG






PTCH1
1935
CCTGAAACAAGGCTGAGAATCCCG
1936
CCACGACAAAGCCGACTACATGCCTGAAACAAGGCTGAGAAT







CCCGGCAGCAGAGCCCATCGAGTA






PTEN
1939
CCTTTCCAGCTTTACAGTGAATTGCTGCA
1940
TGGCTAAGTGAAGATGACAATCATGTTGCAGCAATTCACTGTA







AAGCTGGAAAGGGACGAACTGGTGTAATGATATGTGCA






PTGER3
1943
CCTTTGCCTTCCTGGGGCTCTT
1944
TAACTGGGGCAACCTTTTCTTCGCCTCTGCCTTTGCCTTCCTG







GGGCTCTTGGCGCTGACAGTCACCTTTTCCTGCAA






PTGS2
1947
CCTACCACCAGCAACCCTGCCA
1948
GAATCATTCACCAGGCAAATTGCTGGCAGGGTTGCTGGTGGTA







GGAATGTTCCACCCGCAGTACAG






PTH1R
1951
CCAGTGCCAGTGTCCAGCGGCT
1952
CGAGGTACAAGCTGAGATCAAGAAATCTTGGAGCCGCTGGAC







ACTGGCACTGGACTTCAAGCGAAAGGCACGC






PTHLH
1955
TGACACCTCCACAACGTCGCTGGA
1956
AGTGACTGGGAGTGGGCTAGAAGGGGACCACCTGTCTGACAC







CTCCACAACGTCGCTGGAGCTCGATTCACGGTAACAGGCTT






PTK2
1959
ACCAGGCCCGTCACATTCTCGTAC
1960
GACCGGTCGAATGATAAGGTGTACGAGAATGTGACGGGCCTG







GTGAAAGCTGTCATCGAGATGTCCAG






PTK2B
1963
CTCCGCAAACCAACCTCCTGGCT
1964
CAAGCCCAGCCGACCTAAGTACAGACCCCCTCCGCAAACCAA







CCTCCTGGCTCCAAAGCTGCAGTTCCAGGTTC






PTK6
1967
AGTGTCTGCGTCCAATACACGCGT
1968
GTGCAGGAAAGGTTCACAAATGTGGAGTGTCTGCGTCCAATAC







ACGCGTGTGCTCCTCTCCTTACTCCATCGTGTGTGC






PTK7
1971
CGCAAGGTCCCATTCTTGAAGACC
1972
TCAGAGGACTCACGGTTCGAGGTCTTCAAGAATGGGACCTTGC







GCATCAACAGCGTGGAGGTGTATG






PTPN1
1975
CTGATCCAGACAGCCGACCAGCT
1976
AATGAGGAAGTTTCGGATGGGGCTGATCCAGACAGCCGACCA







GCTGCGCTTCTCCTACCTGGCTGTGATCGAAG






PTPRK
1979
CCCCATCGTTGTACATTGCAGTGC
1980
TCAAACCCTCCCAGTGCTGGCCCCATCGTTGTACATTGCAGTG







CTGGTGCTGGACGAACTGGCTGCT






PTTG1
1983
CACACGGGTGCCTGGTTCTCCA
1984
GGCTACTCTGATCTATGTTGATAAGGAAAATGGAGAACCAGGC







ACCCGTGTGGTTGCTAAGGATGGGCTGAAGC






PYCARD
1987
ACGTTTGTGACCCTCGCGATAAGC
1988
CTTTATAGACCAGCACCGGGCTGCGCTTATCGCGAGGGTCAC







AAACGTTGAGTGGCTGCTGGATGCT






RAB27A
1991
ACAAATTGCTTCTCACCATCCCCATT
1992
TGAGAGATTAATGGGCATTGTGTACAAATTGCTTCTCACCATCC







CCATTAGACCTACGAATAAAGCATCCGG






RAB30
1995
CCATCAGGGCAGTTGCTGATTCCT
1996
TAAAGGCTGAGGCACGGAGAAGAAAAGGAATCAGCAACTGCC







CTGATGGGCCATGAGATGCTGGGGAG






RAB31
1999
CTTCTCAAAGTGAGGTGCCAGGCC
2000
CTGAAGGACCCTACGCTCGGTGGCCTGGCACCTCACTTTGAG







AAGAGTGAGCACACTGGCTTTGCAT






RAD21
2003
CACTTAAAACGAATCTCAAGAGGGTGAC
2004
TAGGGATGGTATCTGAAACAACAATGGTCACCCTCTTGAGATT





CA

CGTTTTAAGTGTAATTCCATAATGAGCAGAGGTGTACGCGA






RAD51
2007
CTTTCAGCCAGGCAGATGCACTTG
2008
AGACTACTCGGGTCGAGGTGAGCTTTCAGCCAGGCAGATGCA







CTTGGCCAGGTTTCTGCGGATGCT






RAD9A
2011
CTTTGCTGGACGGCCACTTTGTCT
2012
GCCATCTTCACCATCAAGGACTCTTTGCTGGACGGCCACTTTG







TCTTGGCCACACTCTCAGACACCG






RAF1
2015
TCCAGGATGCCTGTTAGTTCTCAGCA
2016
CGTCGTATGCGAGAGTCTGTTTCCAGGATGCCTGTTAGTTCTC







AGCACAGATATTCTACACCTCACGCCTTCA






RAGE
2019
CCGGAGTGTCTATTCCAAGCAGCC
2020
ATTAGGGGACTTTGGCTCCTGCCGGAGTGTCTATTCCAAGCAG







CCGTACACGGAATACATCTCCACCC






RALA
2023
TTGTGTTTCTTGGGCAGTCTTTCTTGAA
2024
TGGTCCTGAATGTAGCGTGTAAGCTTGTGTTTCTTGGGCAGTC







TTTCTTGAAATTGAAGAGGTGAAATGGGG






RALBP1
2027
TGCTGTCCTGTCGGTCTCAGTACGTTCA
2028
GGTGTCAGATATAAATGTGCAAATGCCTTCTTGCTGTCCTGTC







GGTCTCAGTACGTTCACTTTATAGCTGCTGGCAATATCGAA






RAP1B
2031
CACGCATGATGCAAGCTTGTCAAA
2032
TGACAGCGTGAGAGGTACTAGGTTTTGACAAGCTTGCATCATG







CGTGAGTATAAGCTAGTCGTTCTTGGCTCAG






RARB
2035
TGTGCTCTGCTGTGTTCCCACTTG
2036
ATGAACCCTTGACCCCAAGTTCAAGTGGGAACACAGCAGAGC







ACAGTCCTAGCATCTCACCCAGCTC






RASSF1
2039
CACCACCAAGAACTTTCGCAGCAG
2040
AGGGCACGTGAAGTCATTGAGGCCCTGCTGCGAAAGTTCTTG







GTGGTGGATGACCCCCGCAAGTTTGCACTCTTT






RB1
2043
CCCTTACGGATTCCTGGAGGGAAC
2044
CGAAGCCCTTACAAGTTTCCTAGTTCACCCTTACGGATTCCTG







GAGGGAACATCTATATTTCACCCCTGAAGAGTCC






RECK
2047
TCAAGTGTCCTTCGCTCTTGGCAG
2048
GTCGCCGAGTGTGCTTCTGTCAAGTGTCCTTCGCTCTTGGCAG







CTGGATGCAAACCCATCATCCCAC






REG4
2051
TCCTCTTCCTTTCTGCTAGCCTGGC
2052
TGCTAACTCCTGCACAGCCCCGTCCTCTTCCTTTCTGCTAGCC







TGGCTAAATCTGCTCATTATTTCAGAGGGGAAACCTAGCA






RELA
2055
CTGAGCTCTGCCCGGACCGCT
2056
CTGCCGGGATGGCTTCTATGAGGCTGAGCTCTGCCCGGACCG







CTGCATCCACAGTTTCCAGAACCTGG






RFX1
2059
TCCAATGGACCAAGCACTGTGACA
2060
TCCTCTCCAAGTTCGAGCCCGTGCTCCAATGGACCAAGCACTG







TGACAACGTGCTGTACCAGGGCCTG






RGS10
2063
AGTTCCAGCAGCAGCCACCAGAG
2064
AGACATCCACGACAGCGATGGCAGTTCCAGCAGCAGCCACCA







GAGCCTCAAGAGCACAGCCAAATGG






RGS7
2067
TGAAAATGAACTCCCACTTCCGGG
2068
CAGGCTGCAGAGAGCATTTGCCCGGAAGTGGGAGTTCATTTTC







ATGCAAGCAGAAGCACAAGCAAA






RHOA
2071
AAATGGGCTCAACCAGAAAAGCCC
2072
TGGCATAGCTCTGGGGTGGGCAGTTTTTTGAAAATGGGCTCAA







CCAGAAAAGCCCAAGTTCATGCAGCTGTGGCA






RHOB
2075
CTTTCCAACCCCTGGGGAAGACAT
2076
AAGCATGAACAGGACTTGACCATCTTTCCAACCCCTGGGGAAG







ACATTTGCAACTGACTTGGGGAGG






RHOC
2079
TCCGGTTCGCCATGTCCCG
2080
CCCGTTCGGTCTGAGGAAGGCCGGGACATGGCGAACCGGATC







AGTGCCTTTGGCTACCTTGAGTGCTC






RLN1
2083
TGAGAGGCAACCATCATTACCAGAGC
2084
AGCTGAAGGCAGCCCTATCTGAGAGGCAACCATCATTACCAG







AGCTACAGCAGTATGTACCTGCATTAAAGGATTCCAA






RND3
2087
TTTTAAGCCTGACTCCTCACCGCG
2088
TCGGAATTGGACTTGGGAGGCGCGGTGAGGAGTCAGGCTTAA







AACTTGTTGGAGGGGAGTAACCAG






RNF114
2091
CCAGGTCAGCCCTTCTCTTCCCTT
2092
TGACAGGGGAAGTGGGTCCCCAGGTCAGCCCTTCTCTTCCCT







TTGGGCTCTTGCCAAAGCTGTCTTCC






ROBO2
2095
CTGTACCATCCACTGCCAGCGTTT
2096
CTACAAGGCCCAGCCAACCAAACGCTGGCAGTGGATGGTACA







GCGTTACTGAAATGTAAAGCCACTGGTG






RRM1
2099
CATTGGAATTGCCATTAGTCCCAGC
2100
GGGCTACTGGCAGCTACATTGCTGGGACTAATGGCAATTCCAA







TGGCCTTGTACCGATGCTGAGAG






RRM2
2103
CCAGCACAGCCAGTTAAAAGATGCA
2104
CAGCGGGATTAAACAGTCCTTTAACCAGCACAGCCAGTTAAAA







GATGCAGCCTCACTGCTTCAACGCAGAT






S100P
2107
TTGCTCAAGGACCTGGACGCCAA
2108
AGACAAGGATGCCGTGGATAAATTGCTCAAGGACCTGGACGC







CAATGGAGATGCCCAGGTGGACTTC






SAT1
2111
TCCAGTGCTCTTTCGGCACTTCTG
2112
CCTTTTACCACTGCCTGGTTGCAGAAGTGCCGAAAGAGCACTG







GACTCCGGAAGGACACAGCATTGT






SCUBE2
2115
CAGGCCCTCTTCCGAGCGGT
2116
TGACAATCAGCACACCTGCATTCACCGCTCGGAAGAGGGCCT







GAGCTGCATGAATAAGGATCACGGCTGTAGTCACA






SDC1
2119
CTCTGAGCGCCTCCATCCAAGG
2120
GAAATTGACGAGGGGTGTCTTGGGCAGAGCTGGCTCTGAGCG







CCTCCATCCAAGGCCAGGTTCTCCGTTAGCTCCT






SDC2
2123
AACTCCATCTCCTTCCCCAGGCAT
2124
GGATTGAAGTGGCTGGAAAGAGTGATGCCTGGGGAAGGAGAT







GGAGTTATGAGGGTACTGTGGCTGGT






SDHC
2127
TTACATCCTCCCTCTCCCCGCAAT
2128
CTTCCCTCGGGTCTCAGGCATTTACATCCTCCCTCTCCCCGCA







ATCTGACCTTTACCAGGAGGGAA






SEC14L1
2131
CGGGCTTCTACATCCTGCAGTGG
2132
AGGGTTCCCATGTGACCAGGTGGCCGGGCTTCTACATCCTGC







AGTGGAAATTCCACAGCATGCCTGC






SEC23A
2135
TCCTGGAGATGAAATGCTGTCCCA
2136
CGTGTGCATTAGATCAGACAGGTCTCCTGGAGATGAAATGCTG







TCCCAACCTTACTGGAGGATACATGGTAATGGG






SEMA3A
2139
TTGCCAATAGACCAGCGCTCTCTG
2140
TTGGAATGCAGTCCGAAGTCGCAGAGAGCGCTGGTCTATTGG







CAATTCCAGAGGCGAAATGAAGAG






SEPT9
2143
TTGCCAATAGACCAGCGCTCTCTG
2144
CAGTGACCACGAGTACCAGGTCAACGGCAAGAGGATCCTTGG







GAGGAAGACCAAGTGGGGTACCATCGAAG






SERPINA3
2147
AGGGAATCGCTGTCACCTTCCAAG
2148
GTGTGGCCCTGTCTGCTTATCCTTGGAAGGTGACAGCGATTCC







CTGTGTAGCTCTCACATGCACAGGG






SERPINB5
2151
AGCTGACAACAGTGTGAACGACCAGACC
2152
CAGATGGCCACTTTGAGAACATTTTAGCTGACAACAGTGTGAA







CGACCAGACCAAAATCCTTGTGGTTAATGCTGCC






SESN3
2155
TGCTCTTCTCCTCGTCTGGCAAAG
2156
GACCCTGGTTTTGGGTATGAAGACTTTGCCAGACGAGGAGAA







GAGCATTTGCCAACATTCCGAGCTC






SFRP4
2159
CCTGGGACAGCCTATGTAAGGCCA
2160
TACAGGATGAGGCTGGGCATTGCCTGGGACAGCCTATGTAAG







GCCATGTGCCCCTTGCCCTAACAAC






SH3RF2
2163
AACCGGATGGTCCATTCTCCTTCA
2164
CCATCACAACAGCCTTGAACACTCTCAACCGGATGGTCCATTC







TCCTTCAGGGCGCCATATGGTAGAGATCAGCACCCCAGTG






SH3YL1
2167
CACAGCAGTCATCTGCACCAGTCC
2168
CCTCCAAAGCCATTGTCAAGACCACAGCAGTCATCTGCACCAG







TCCAGCTGAACTCTGGCTCTCAAAG






SHH
2171
CACCGAGTTCTCTGCTTTCACCGA
2172
GTCCAAGGCACATATCCACTGCTCGGTGAAAGCAGAGAACTC







GGTGGCGGCCAAATCGGGAGGCTGCTTC






SHMT2
2175
CCATCACTGCCAACAAGAACACCTG
2176
AGCGGGTGCTAGAGCTTGTATCCATCACTGCCAACAAGAACAC







CTGTCCTGGAGACCGAAGTGCCAT






SIM2
2179
CGCCTCTCCACGCACTCAGCTAT
2180
GATGGTAGGAAGGGATGTGCCCGCCTCTCCACGCACTCAGCT







ATACCTCATTCACAGCTCCTTGTG






SIPA1L1
2183
CGCCACAATGCCCTCATAGTTGAC
2184
CTAGGACAGCTTGGCTTCCATGTCAACTATGAGGGCATTGTGG







CGGATGTGGAGCCCTACGGTTATG






SKIL
2187
CCAATCTCTGCCTCAGTTCTGCCA
2188
AGAGGCTGAATATGCAGGACAGTTGGCAGAACTGAGGCAGAG







ATTGGACCATGCTGAGGCCGATAG






SLC22A3
2191
CAGCATCCACGCATTGACACAGAC
2192
ATCGTCAGCGAGTTTGACCTTGTCTGTGTCAATGCGTGGATGC







TGGACCTCACCCAAGCCATCCTG






SLC25A21
2195
TCATGGTGCTGCATAGCAAATATCCA
2196
AAGTGTTTTTCCCCCTTGAGATAATGGATATTTGCTATGCAGCA







CCATGAAGAAGAGAGACTATCGATCGGCC






SLC44A1
2199
TACCATGGCTGCTGCTCTTCATCC
2200
AGGACCGTAGCTGCACAGACATACCATGGCTGCTGCTCTTCAT







CCTCTTCTGCATTGGGATGGGAT






SMAD4
2203
TGCATTCCAGCCTCCCATTTCCA
2204
GGACATTACTGGCCTGTTCACAATGAGCTTGCATTCCAGCCTC







CCATTTCCAATCATCCTGCTCCTGAGTATTGGT






SMARCC2
2207
TATCTTACCTCTACCGCCTGCCGC
2208
TACCGACTGAACCCCCAAGAGTATCTTACCTCTACCGCCTGCC







GCCGAAACCTAGCGGGTGATGTC






SMARCD1
2211
CCCACCCTTGCTGTGTTGAGTCTG
2212
CCGAGTTAGCATATCCCAGGCTCGCAGACTCAACACAGCAAG







GGTGGGAGACAGCTGGGCACAAAGG






SMO
2215
CTTCACAGAGGCTGAGCACCAGGA
2216
GGCATCCAGTGCCAGAACCCGCTCTTCACAGAGGCTGAGCAC







CAGGACATGCACAGCTACATCGCG






SNAI1
2219
TCTGGATTAGAGTCCTGCAGCTCGC
2220
CCCAATCGGAAGCCTAACTACAGCGAGCTGCAGGACTCTAAT







CCAGAGTTTACCTTCCAGCAGCCCTAC






SNRPB2
2223
CCCACCTAAGGCCTACGCCGACTA
2224
CGTTTCCTGCTTTTGGTTCTTACAGTAGTCGGCGTAGGCCTTA







GGTGGGTTCGTGCGCCTTCTACCT






SOD1
2227
TTTGTCAGCAGTCACATTGCCCAA
2228
TGAAGAGAGGCATGTTGGAGACTTGGGCAATGTGACTGCTGA







CAAAGATGGTGTGGCCGATGTGTCTATT






SORBS1
2231
ATTTCCATTGGCATCAGCACTGGA
2232
GCAGATGAGTGGAGGCTTTCTTCCAGTGCTGATGCCAATGGAA







ATGCCCAGCCCTCTTCACTCGCT






SOX4
2235
CGAGTCCAGCATCTCCAACCTGGT
2236
AGATGATCTCGGGAGACTGGCTCGAGTCCAGCATCTCCAACC







TGGTTTTCACCTACTGAAGGGCGC






SPARC
2239
TGGACCAGCACCCCATTGACGG
2240
TCTTCCCTGTACACTGGCAGTTCGGCCAGCTGGACCAGCACC







CCATTGACGGGTACCTCTCCCACACCGAGCT






SPARCL1
2243
ACTTCATCCCAAGCCAGGCCTTTC
2244
GGCACAGTGCAAGTGATGACTACTTCATCCCAAGCCAGGCCTT







TCTGGAGGCCGAGAGAGCTCAATC






SPDEF
2247
ATCATCCGGAAGCCAGACATCTCC
2248
CCATCCGCCAGTATTACAAGAAGGGCATCATCCGGAAGCCAG







ACATCTCCCAGCGCCTCGTCTACCAGTTCGTGCACCC






SPINK1
2251
ACCACGTCTCTTCAGAAGCCTGGG
2252
CTGCCATATGACCCTTCCAGTCCCAGGCTTCTGAAGAGACGTG







GTAAGTGCGGTGCAGTTTTCAAC






SPINT1
2255
CTGTCGCAGTGTTCCTGGTCATCTGC
2256
ATTCCCAGCACAGGCTCTGTGGAGATGGCTGTCGCAGTGTTC







CTGGTCATCTGCATTGTGGTGGTGGTAGCCATCT






SPP1
2259
TGAATGGTGCATACAAGGCCATCC
2260
TCACACATGGAAAGCGAGGAGTTGAATGGTGCATACAAGGCC







ATCCCCGTTGCCCAGGACCTGAAC






SQLE
2263
TGGGCAAGAAAAACATCTCATTCCTTTG
2264
ATTTTCGAGGCCAAAAAATCATTTTACTGGGCAAGAAAAACATC







TCATTCCTTTGTCGTGAATATCCTTGCTCAGG






SRC
2267
AACCGCTCTGACTCCCGTCTGGTG
2268
TGAGGAGTGGTATTTTGGCAAGATCACCAGACGGGAGTCAGA







GCGGTTACTGCTCAATGCAGAGAACCCGAGAG






SRD5A1
2271
CCTCTCTCGGAGGCCACAGAGGCT
2272
GGGCTGGAATCTGTCTAGGAGCCCTCTCTCGGAGGCCACAGA







GGCTGGGGGTAGCCATTGTGCAGTCATGG






SRD5A2
2275
AGACACCACTCAGAATCCCCAGGC
2276
GTAGGTCTCCTGGCGTTCTGCCAGCTGGCCTGGGGATTCTGA







GTGGTGTCTGCTTAGAGTTTACTCCTACCCTTCCAGGGA






STS
2279
AGTCACGAGCACCCAGCGAAACTT
2280
CCTGTCCTGCCAGAGCATGGATGAAGTTTCGCTGGGTGCTCGT







GACTGGCCAGTTTTGTGCAGCTG






STAT1
2283
TGGCAGTTTTCTTCTGTCACCAAAA
2284
GGGCTCAGCTTTCAGAAGTGCTGAGTTGGCAGTTTTCTTCTGT







CACCAAAAGAGGTCTCAATGTGGACCAGCTGAACATGT






STAT3
2287
TCCTGGGAGAGATTGACCAGCA
2288
TCACATGCCACTTTGGTGTTTCATAATCTCCTGGGAGAGATTGA







CCAGCAGTATAGCCGCTTCCTGCAAG






STAT5A
2291
CGGTTGCTCTGCACTTCGGCCT
2292
GAGGCGCTCAACATGAAATTCAAGGCCGAAGTGCAGAGCAAC







CGGGGCCTGACCAAGGAGAACCTCGTGTTCCTGGC






STAT5B
2295
CAGCCAGGACAACAATGCGACGG
2296
CCAGTGGTGGTGATCGTTCATGGCAGCCAGGACAACAATGCG







ACGGCCACTGTTCTCTGGGACAATGCTTTTGC






STMN1
2299
CACGTTCTCTGCCCCGTTTCTTG
2300
AATACCCAACGCACAAATGACCGCACGTTCTCTGCCCCGTTTC







TTGCCCCAGTGTGGTTTGCATTGTCTCC






STS
2303
CTGCGTGGCTCTCGGCTTCCCA
2304
GAAGATCCCTTTCCTCCTACTGTTCTTTCTGTGGGAAGCCGAG







AGCCACGCAGCATCAAGGCCGAACATCATCC






SULF1
2307
TACCGTGCCAGCAGAAGCCAAAG
2308
TGCAGTTGTAGGGAGTCTGGTTACCGTGCCAGCAGAAGCCAA







AGAAAGAGTCAACGGCAATTCTTGAGA






SUMO1
2311
CTGACCAGGAGGCAAAACCTTCAACTGA
2312
GTGAAGCCACCGTCATCATGTCTGACCAGGAGGCAAAACCTTC







AACTGAGGACTTGGGGGATAAGAAGGAAGG






SVIL
2315
ACCCCAGGACTGATGTCAAGGCAT
2316
ACTTGCCCAGCACAAGGAAGACCCCAGGACTGATGTCAAGGC







ATACGATGTGACACGGATGGTGTC






TAF2
2319
AGCCTCCAAACACAGTGACCACCA
2320
GCGCTCCACTCTCAGTCTTTACTAAGGAATCTACAGCCTCCAA







ACACAGTGACCACCATCACCACCATCACCATGAGCACAAG






TARP
2323
TCTTCATGGTGTTCCCCTCCTGG
2324
GAGCAACACGATTCTGGGATCCCAGGAGGGGAACACCATGAA







GACTAACGACACATACATGAAATTTAGCTGGTTAACGGTGCC






TBP
2327
TACCGCAGCAAACCGCTTGGG
2328
GCCCGAAACGCCGAATATAATCCCAAGCGGTTTGCTGCGGTA







ATCATGAGGATAAGAGAGCCACG






TFDP1
2331
CGCACCAGCATGGCAATAAGCTTT
2332
TGCGAAGTGCTTTTGTTTGTTTGTTTTCGTTTGGTTAAAGCTTAT







TGCCATGCTGGTGCGGCTATGGAGACTGTCTGGAAGGC






TFF1
2335
TGCTGTTTCGACGACACCGTTCG
2336
GCCCTCCCAGTGTGCAAATAAGGGCTGCTGTTTCGACGACAC







CGTTCGTGGGGTCCCCTGGTGCTTCTATCCTAATACCATCGAC







G






TFF3
2339
CAGAAGCGCTTGCCGGGAGCAAAGG
2340
AGGCACTGTTCATCTCAGCTTTTCTGTCCCTTTGCTCCCGGCA







AGCGCTTCTGCTGAAAGTTCATATCTGGAGCCTGATG






TGFA
2343
TTGGCCTGTAATCACCTGTGCAGCCTT
2344
GGTGTGCCACAGACCTTCCTACTTGGCCTGTAATCACCTGTGC







AGCCTTTTGTGGGCCTTCAAAACTCTGTCAAGAACTCCGT






TGFB1I1
2347
CAAGATGTGGCTTCTGCAACCAGC
2348
GCTACTTTGAGCGCTTCTCGCCAAGATGTGGCTTCTGCAACCA







GCCCATCCGACACAAGATGGTGACC






TGFB2
2351
TCCTGAGCCCGAGGAAGTCCC
2352
ACCAGTCCCCCAGAAGACTATCCTGAGCCCGAGGAAGTCCCC







CCGGAGGTGATTTCCATCTACAACAGCACCAGG






TGFB3
2355
CGGCCAGATGAGCACATTGCC
2356
GGATCGAGCTCTTCCAGATCCTTCGGCCAGATGAGCACATTGC







CAAACAGCGCTATATCGGTGGC






TGFBR2
2359
TTCTGGGCTCCTGATTGCTCAAGC
2360
AACACCAATGGGTTCCATCTTTCTGGGCTCCTGATTGCTCAAG







CACAGTTTGGCCTGATGAAGAGG






THBS2
2363
TGAGTCTGCCATGACCTGTTTTCCTTCAT
2364
CAAGACTGGCTACATCAGAGTCTTAGTGCATGAAGGAAAACAG







GTCATGGCAGACTCAGGACCTATCTATGACCAAACCTACGCTG






THY1
2367
CAAGCTCCCAAGAGCTTCCAGAGC
2368
GGACAAGACCCTCTCAGGCTGTCCCAAGCTCCCAAGAGCTTC







CAGAGCTCTGACCCACAGCCTCCAA






TIAM1
2371
TGGAGCCCTTCTCCCAAGATGGTA
2372
GTCCCTGGCTGAAAATGGCCTGGAGCCCTTCTCCCAAGATGG







TACCCTAGAAGACTTCGGGAGCCC






TIMP2
2375
CCCTGGGACACCCTGAGCACCA
2376
TCACCCTCTGTGACTTCATCGTGCCCTGGGACACCCTGAGCAC







CACCCAGAAGAAGAGCCTGAACCACA






TIMP3
2379
CCAAGAACGAGTGTCTCTGGACCG
2380
CTACCTGCCTTGCTTTGTGACTTCCAAGAACGAGTGTCTCTGG







ACCGACATGCTCTCCAATTTCGGT






TK1
2383
CAAATGGCTTCCTCTGGAAGGTCCCA
2384
GCCGGGAAGACCGTAATTGTGGCTGCACTGGATGGGACCTTC







CAGAGGAAGCCATTTGGGGCCATCCTGAACCTGGTGCCGCTG






TMPRSS2
2387
AAGCACTGTGCATCACCTTGACCC
2388
GGACAGTGTGCACCTCAAAGACTAAGAAAGCACTGTGCATCAC







CTTGACCCTGGGGACCTTCCTCGTGGGAG






TMPRSS2
2391
TAAGGCTTCCTGCCGCGCTCCA
2392
GAGGCGGAGGCGGAGGGCGAGGGGCGGGGAGCGCCGCCTG



ERGA



GAGCGCGGCAGGAAGCCTTATCAGTTGTGAGTGAGGACCAGT






TMPRSS2
2395
CCTGGAATAACCTGCCGCGC
2396
GAGGCGGAGGGCGAGGGGCGGGGAGCGCCGCCTGGAGCGC



ERGB



GGCAGGTTATTCCAGGATCTTTGGAGACCCGAGGAA






TNF
2399
CGCTGAGATCAATCGGCCCGACTA
2400
GGAGAAGGGTGACCGACTCAGCGCTGAGATCAATCGGCCCGA







CTATCTCGACTTTGCCGAGTCTGGGCA






TNFRSF10A
2403
CAATGCTTCCAACAATTTGTTTGCTTGCC
2404
TGCACAGAGGGTGTGGGTTACACCAATGCTTCCAACAATTTGT







TTGCTTGCCTCCCATGTACAGCTTGTAAATCAGATGAAGA






TNFRSF10B
2407
CAGACTTGGTGCCCTTTGACTCC
2408
CTCTGAGACAGTGCTTCGATGACTTTGCAGACTTGGTGCCCTT







TGACTCCTGGGAGCCGCTCATGAGGAAGTTGGGCCTCATGG






TNFRSF18
2411
CCTTCTCCTCTGCCGATCGCTC
2412
CAGAAGCTGCCAGTTCCCCGAGGAAGAGCGGGGCGAGCGAT







CGGCAGAGGAGAAGGGGCGGCTGGGAGACCTGTGGGTG






TNFSF10
2415
AAGTACACGTAAGTTACAGCCACACA
2416
CTTCACAGTGCTCCTGCAGTCTCTCTGTGTGGCTGTAACTTAC







GTGTACTTTACCAACGAGCTGAAGCAGATG






TNFSF11
2419
ACATGACCAGGGACCAACCCCTC
2420
AACTGCATGTGGGCTATGGGAGGGGTTGGTCCCTGGTCATGT







GCCCCTTCGCAGCTGAAGTGGAGAGGGTGTCA






TOP2A
2423
CATATGGACTTTGACTCAGCTGTGGC
2424
AATCCAAGGGGGAGAGTGATGACTTCCATATGGACTTTGACTC







AGCTGTGGCTCCTCGGGCAAAATCTGTAC






TP53
2427
AAGTCCTGGGTGCTTCTGACGCACA
2428
CTTTGAACCCTTGCTTGCAATAGGTGTGCGTCAGAAGCACCCA







GGACTTCCATTTGCTTTGTCCCGGG






TP63
2431
CCCGGGTCTCACTGGAGCCCA
2432
CCCCAAGCAGTGCCTCTACAGTCAGTGTGGGCTCCAGTGAGA







CCCGGGGTGAGCGTGTTATTGATGCTGTGCGATTC






TPD52
2435
TCTGCTACCCACTGCCAGATGCTG
2436
GCCTGTGAGATTCCTACCTTTGTTCTGCTACCCACTGCCAGAT







GCTGCAAGCGAGGTCCAAGCACAT






TPM1
2439
TTCTCCAGCTGACCCTGGTTCTCTC
2440
TCTCTGAGCTCTGCATTTGTCTATTCTCCAGCTGACCCTGGTTC







TCTCTCTTAGCATCCTGCCTTAGAGCC






TPM2
2443
CCAAGCACATCGCTGAGGATTCAG
2444
AGGAGATGCAGCTGAAGGAGGCCAAGCACATCGCTGAGGATT







CAGACCGCAAATATGAAGAGGTGG






TPP2
2447
ATCCTGTTCAGGTGGCTGCACCTT
2448
TAACCGTGGCATCTACCTCCGAGATCCTGTTCAGGTGGCTGCA







CCTTCAGATCATGGCGTTGGCAT






TPX2
2451
CAGGTCCCATTGCCGGGCG
2452
TCAGCTGTGAGCTGCGGATACCGCCCGGCAATGGGACCTGCT







CTTAACCTCAAACCTAGGACCGT






TRA2A
2455
AACTGAGGCCAAACACTCCAAGGC
2456
GCAAATCCAGATCCCAACACTTGCCTTGGAGTGTTTGGCCTCA







GTTTGTACACAACAGAGAGGGATCTTCGTGAAG






TRAF3IP2
2459
TGGATCTGCCAACCATAGACACGG
2460
CCTCACAGGAACCGAGCAGGCCTGGATCTGCCAACCATAGAC







ACGGGATATGATTCCCAGCCCCAG






TRAM1
2463
AGTGCTGAGCCACGAATTCGTCC
2464
CAAGAAAAGCACCAAGAGCCCCCCAGTGCTGAGCCACGAATT







CGTCCTGCAGAATCACGCGGACAT






TRAP1
2467
TTCGGCGATTTCAAACACTCCAGA
2468
TTACCAGTGGCTTTCAGATGGTTCTGGAGTGTTTGAAATCGCC







GAAGCTTCGGGAGTTAGAACCGGGACA






TRIM14
2471
AACTGCCAGCTCTCAGACCCTTCC
2472
CATTCGCCTTAAGGAAAGCATAAACTGCCAGCTCTCAGACCCT







TCCAGCACCAAGCCAGGTACCTTG






TRO
2475
CCACCCAAGGCCAAATTACCAATG
2476
GCAACTGCCACCCATACAGCTACCACCCAAGGCCAAATTACCA







ATGAGACAGCCAGTATCCACACCA






TRPC6
2479
CTTCTCCCAGCTCCGAGTCCATG
2480
CGAGAGCCAGGACTATCTGCTCATGGACTCGGAGCTGGGAGA







AGACGGCTGCCCGCAAGCCCCGCTGCCTTGCTACGGCTA






TRPV6
2483
ACTTTGGGGAGCACCCTTTGTCCT
2484
CCGTAGTCCCTGCAACCTCATCTACTTTGGGGAGCACCCTTTG







TCCTTTGCTGCCTGTGTGAACAGTGAGGA






TSTA3
2487
AACGTGCACATGAACGACAACGTC
2488
CAATTTGGACTTCTGGAGGAAAAACGTGCACATGAACGACAAC







GTCCTGCACTCGGCCTTTGAGGTG






TUBB2A
2491
TCTCAGATCAATCGTGCATCCTTAGTGAA
2492
CGAGGACGAGGCTTAAAAACTTCTCAGATCAATCGTGCATCCT







TAGTGAACTTCTGTTGTCCTCAAGCATGGT






TYMP
2495
ACAGCCTGCCACTCATCACAGCC
2496
CTATATGCAGCCAGAGATGTGACAGCCACCGTGGACAGCCTG







CCACTCATCACAGCCTCCATTCTCAGTAAGAAACTCGTGG






TYMS
2499
CATCGCCAGCTACGCCCTGCTC
2500
GCCTCGGTGTGCCTTTCAACATCGCCAGCTACGCCCTGCTCAC







GTACATGATTGCGCACATCACG






UAP1
2503
TACCTGTAAACCTTTCTCGGCGCG
2504
CTGGAGACGGTCGTAGCTGCGGTCGCGCCGAGAAAGGTTTAC







AGGTACATACATTACACCCCTATTTCTACAAAGCTTGGC






UBE2C
2507
TCTGCCTTCCCTGAATCAGACAACC
2508
TGTCTGGCGATAAAGGGATTTCTGCCTTCCCTGAATCAGACAA







CCTTTTCAAATGGGTAGGGACCAT






UBE2G1
2511
TTGTCCCACCAGTGCCTCATCAGT
2512
TGACACTGAACGAGGTGGCTTTTGTCCCACCAGTGCCTCATCA







GTGTGAGGCGATTCCTCTCTGCTT






UBE2T
2515
AGGTGCTTGGAGACCATCCCTCAA
2516
TGTTCTCAAATTGCCACCAAAAGGTGCTTGGAGACCATCCCTC







AACATCGCAACTGTGTTGACCTCT






UGDH
2519
TATACAGCACACAGGGCCTGCACA
2520
GAAACTCCAGAGGGCCAGAGAGCTGTGCAGGCCCTGTGTGCT







GTATATGAGCACTGGGTTCCCAGAG






UGT2B15
2523
AAAGATGGGACTCCTCCTTTATTTCAGCA
2524
AAGCCTGAAGTGGAATGACTGAAAGATGGGACTCCTCCTTTAT







TTCAGCATGGAGGGTTTTAAATGGAGG






UGT2B17
2527
ACCCGAAGGTGCTTGGCTCCTTTA
2528
TTGAGTTTGTCATGCGCCATAAAGGAGCCAAGCACCTTCGGGT







CGCAGCCCACAACCTCACCTGGA






UHRF1
2531
CGGCCATACCCTCTTCGACTACGA
2532
CTACAGGGGCAAACAGATGGAGGACGGCCATACCCTCTTCGA







CTACGAGGTCCGCCTGAATGACACC






UTP23
2535
TCGAAATTGTCCTCATTTCAAGAATGCA
2536
GATTGCACAAAAATGCCAAGTTCGAAATTGTCCTCATTTCAAGA







ATGCAGTGAGTGGATCAGAATGTCTGCTTTCC






VCAM1
2539
CAGGCACACACAGGTGGGACACAAAT
2540
TGGCTTCAGGAGCTGAATACCCTCCCAGGCACACACAGGTGG







GACACAAATAAGGGTTTTGGAACCACTATTTTCTCATCACGACA







GCA






VCL
2543
AGTGGCAGCCACGGCGCC
2544
GATACCACAACTCCCATCAAGCTGTTGGCAGTGGCAGCCACG







GCGCCTCCTGATGCGCCTAACAGGGA






VCPIP1
2547
TGGTCCATCCTCTGCACCTGCTAC
2548
TTTCTCCCAGTACCATTCGTGATGGTCCATCCTCTGCACCTGC







TACACCTACCAAGGCTCCCTATTCA






VDR
2551
CAGCATGAAGCTAACGCCCCTTGT
2552
CCTCTCCTTCCAGCCTGAGTGCAGCATGAAGCTAACGCCCCTT







GTGCTCGAAGTGTTTGGCAATGA






VEGFA
2555
TTGCCTTGCTGCTCTACCTCCACCA
2556
CTGCTGTCTTGGGTGCATTGGAGCCTTGCCTTGCTGCTCTACC







TCCACCATGCCAAGTGGTCCCAGGCTGC






VEGFB
2559
CTGGGCAGCACCAAGTCCGGA
2560
TGACGATGGCCTGGAGTGTGTGCCCACTGGGCAGCACCAAGT







CCGGATGCAGATCCTCATGATCCGGTACC






VEGFC
2563
CCTCTCTCTCAAGGCCCCAAACCAGT
2564
CCTCAGCAAGACGTTATTTGAAATTACAGTGCCTCTCTCTCAAG







GCCCCAAACCAGTAACAATCAGTTTTGCCAATCACACTT






VIM
2567
ATTTCACGCATCTGGCGTTCCA
2568
TGCCCTTAAAGGAACCAATGAGTCCCTGGAACGCCAGATGCG







TGAAATGGAAGAGAACTTTGCCGTTGAAGC






VTI1B
2571
CGAAACCCCATGATGTCTAAGCTTCG
2572
ACGTTATGCACCCCTGTCTTTCCGAAACCCCATGATGTCTAAG







CTTCGAAACTACCGGAAGGACCTTGCTAAACTCCATCGG






WDR19
2575
CCCCTCGACGTATGTCTCCCATTC
2576
GAGTGGCCCAGATGTCCATAAGAATGGGAGACATACGTCGAG







GGGTTAACCAAGCCCTCAAGCATC






WFDC1
2579
CTATGAGTGCCACATCCTGAGCCC
2580
ACCCCTGCTCTGTCCCTCGGGCTATGAGTGCCACATCCTGAG







CCCAGGTGACGTGGCCGAAGGTAT






WISP1
2583
CGGGCTGCATCAGCACACGC
2584
AGAGGCATCCATGAACTTCACACTTGCGGGCTGCATCAGCACA







CGCTCCTATCAACCCAAGTACTGTGGAGTTTG






WNT5A
2587
TTGATGCCTGTCTTCGCGCCTTCT
2588
GTATCAGGACCACATGCAGTACATCGGAGAAGGCGCGAAGAC







AGGCATCAAAGAATGCCAGTATCAATTCCGACA






WWOX
2591
CTGCTGTTTACCTTGGCGAGGCCTTTC
2592
ATCGCAGCTGGTGGGTGTACACACTGCTGTTTACCTTGGCGAG







GCCTTTCACCAAGTCCATGCAACAGGGAGCT






XIAP
2595
TCCCCAAATTGCAGATTTATCAACGGC
2596
GCAGTTGGAAGACACAGGAAAGTATCCCCAAATTGCAGATTTA







TCAACGGCTTTTATCTTGAAAATAGTGCCACGCA






XRCC5
2599
TCTGGCTGAAGGCAGTGTCACCTC
2600
AGCCCACTTCAGCGTCTCCAGTCTGGCTGAAGGCAGTGTCAC







CTCTGTTGGAAGTGTGAATCCTGCT






YY1
2603
TTGATCTGCACCTGCTTCTGCTCC
2604
ACCCGGGCAACAAGAAGTGGGAGCAGAAGCAGGTGCAGATCA







AGACCCTGGAGGGCGAGTTCTCGGTC






ZFHX3
2607
ACCTGGCCCAACTCTACCAGCATC
2608
CTGTGGAGCCTCTGCCTGCGGACCTGGCCCAACTCTACCAGC







ATCAGCTCAATCCAACCCTGCTCC






ZFP36
2611
CAGGTCCCCAAGTGTGCAAGCTC
2612
CATTAACCCACTCCCCTGACCTCACGCTGGGGCAGGTCCCCA







AGTGTGCAAGCTCAGTATTCATGATGGTGGGGG






ZMYND8
2615
CTTTTGCAGGCCAGAATGGAAACC
2616
GGTCTGGGCCAAACTGAAGGGGTTTCCATTCTGGCCTGCAAAA







GCTCTAAGGGATAAAGACGGGCA






ZNF3
2619
AGGAGGTTCCACACTCGCCAGTTC
2620
CGAAGGGACTCTGCTCCAGTGAACTGGCGAGTGTGGAACCTC







CTGACACCTTCTGAGGACCTCCTGC






ZNF827
2623
CCCGCCTTCAGAGAAGAAACCAGA
2624
TGCCTGAGGACCCTCTACCGCCCCCGCCTTCAGAGAAGAAAC







CAGAAAAAGTCACTCCGCCACCTC






ZWINT
2627
ACCAAGGCCCTGACTCAGATGGAG
2628
TAGAGGCCATCAAAATTGGCCTCACCAAGGCCCTGACTCAGAT







GGAGGAAGCCCAGAGGAAACGGA


















TABLE B





microRNA
Sequence
SEQ ID NO







hsa-miR-1
UGGAAUGUAAAGAAGUAUGUAU
2629





hsa-miR-103
GCAGCAUUGUACAGGGCUAUGA
2630





hsa-miR-106b
UAAAGUGCUGACAGUGCAGAU
2631





hsa-miR-10a
UACCCUGUAGAUCCGAAUUUGUG
2632





hsa-miR-133a
UUUGGUCCCCUUCAACCAGCUG
2633





hsa-miR-141
UAACACUGUCUGGUAAAGAUGG
2634





hsa-miR-145
GUCCAGUUUUCCCAGGAAUCCCU
2635





hsa-miR-146b-5p
UGAGAACUGAAUUCCAUAGGCU
2636





hsa-miR-150
UCUCCCAACCCUUGUACCAGUG
2637





hsa-miR-152
UCAGUGCAUGACAGAACUUGG
2638





hsa-miR-155
UUAAUGCUAAUCGUGAUAGGGGU
2639





hsa-miR-182
UUUGGCAAUGGUAGAACUCACACU
2640





hsa-miR-191
CAACGGAAUCCCAAAAGCAGCUG
2641





hsa-miR-19b
UGUAAACAUCCUCGACUGGAAG
2642





hsa-miR-200c
UAAUACUGCCGGGUAAUGAUGGA
2643





hsa-miR-205
UCCUUCAUUCCACCGGAGUCUG
2644





hsa-miR-206
UGGAAUGUAAGGAAGUGUGUGG
2645





hsa-miR-21
UAGCUUAUCAGACUGAUGUUGA
2646





hsa-miR-210
CUGUGCGUGUGACAGCGGCUGA
2647





hsa-miR-22
AAGCUGCCAGUUGAAGAACUGU
2648





hsa-miR-222
AGCUACAUCUGGCUACUGGGU
2649





hsa-miR-26a
UUCAAGUAAUCCAGGAUAGGCU
2650





hsa-miR-27a
UUCACAGUGGCUAAGUUCCGC
2651





hsa-miR-27b
UUCACAGUGGCUAAGUUCUGC
2652





hsa-miR-29b
UAGCACCAUUUGAAAUCAGUGUU
2653





hsa-miR-30a
CUUUCAGUCGGAUGUUUGCAGC
2654





hsa-miR-30e-5p
CUUUCAGUCGGAUGUUUACAGC
2655





hsa-miR-31
AGGCAAGAUGCUGGCAUAGCU
2656





hsa-miR-331
GCCCCUGGGCCUAUCCUAGAA
2657





hsa-miR-425
AAUGACACGAUCACUCCCGUUGA
2658





hsa-miR-449a
UGGCAGUGUAUUGUUAGCUGGU
2659





hsa-miR-486-5p
UCCUGUACUGAGCUGCCCCGAG
2660





hsa-miR-92a
UAUUGCACUUGUCCCGGCCUGU
2661





hsa-miR-93
CAAAGUGCUGUUCGUGCAGGUAG
2662





hsa-miR-99a
AACCCGUAGAUCCGAUCUUGUG
2663








Claims
  • 1.-20. (canceled)
  • 21. A method of analyzing expression of RNA transcripts of genes in a patient with prostate cancer, comprising: measuring a level of an RNA transcript, in a sample from the patient comprising prostate tumor tissue, of a set of genes consisting of: (a) at least one gene selected from the group consisting of genes listed in Table 3A; and (b) at least one gene selected from the group consisting of genes listed in Table 3B; and (c) at least one reference gene.
  • 22. The method of claim 21, wherein the at least one gene selected from the group consisting of genes listed in Table 3A includes at least one of BGN, COL1A1, SFRP4, and TPX2.
  • 23. The method of claim 22, wherein the RNA transcript level of the at least one of BGN, COL1A1, SFRP4, and TPX2 is measured using at least one of the following sets of oligonucleotides: SEQ ID Nos: 257, 258, and 259 (for BGN);SEQ ID Nos: 501, 502, and 503 (for COL1A1);SEQ ID Nos: 2157, 2158, and 2159 (for SFRP4); andSEQ ID Nos: 2449, 2450, and 2451 (for TPX2).
  • 24. The method of claim 21, wherein the at least one gene selected from the group consisting of genes listed in Table 3B includes at least one of FLNC, GSN, GSTM2, TPM2, AZGP1, KLK2, FAM13C, and SRD5A2.
  • 25. The method of claim 24, wherein the RNA transcript level of the at least one of FLNC, GSN, GSTM2, TPM2, AZGP1, KLK2, FAM13C, and SRD5A2 is measured using at least one of the following sets of oligonucleotides: SEQ ID Nos: 929, 930, and 931 (for FLNC);SEQ ID Nos: 1029, 1030, and 1031 (for GSN);SEQ ID Nos: 1037, 1038, and 1039 (for GSTM2);SEQ ID Nos: 2441, 2442, and 2443 (for TPM2);SEQ ID Nos: 225, 226, and 227 (for AZGP1);SEQ ID Nos: 1361, 1362, and 1363 (for KLK2);SEQ ID Nos: 857, 858, and 859 (for FAM13C); andSEQ ID Nos: 2273, 2274, and 2275 (for SRD5A2).
  • 26. The method of claim 21, wherein the at least one gene selected from the group consisting of genes listed in Table 3A includes at least one of BGN, COL1A1, SFRP4, and TPX2; and wherein the at least one gene selected from the group consisting of genes listed in Table 3B includes at least one of FLNC, GSN, GSTM2, TPM2, AZGP1, KLK2, FAM13C, and SRD5A2.
  • 27. The method of claim 26, wherein the RNA transcript level of the at least one of BGN, COL1A1, SFRP4, and TPX2 is measured using at least one of the following sets of oligonucleotides: SEQ ID Nos: 257, 258, and 259 (for BGN);SEQ ID Nos: 501, 502, and 503 (for COL1A1);SEQ ID Nos: 2157, 2158, and 2159 (for SFRP4); andSEQ ID Nos: 2449, 2450, and 2451 (for TPX2); andwherein the RNA transcript level of the at least one of FLNC, GSN, GSTM2, TPM2, AZGP1, KLK2, FAM13C, and SRD5A2 is measured using at least one of the following sets of oligonucleotides:SEQ ID Nos: 929, 930, and 931 (for FLNC);SEQ ID Nos: 1029, 1030, and 1031 (for GSN);SEQ ID Nos: 1037, 1038, and 1039 (for GSTM2);SEQ ID Nos: 2441, 2442, and 2443 (for TPM2);SEQ ID Nos: 225, 226, and 227 (for AZGP1);SEQ ID Nos: 1361, 1362, and 1363 (for KLK2);SEQ ID Nos: 857, 858, and 859 (for FAM13C); andSEQ ID Nos: 2273, 2274, and 2275 (for SRD5A2).
  • 28. The method of claim 21, wherein the at least one gene selected from the group consisting of genes listed in Table 3A includes each of BGN, COL1A1, SFRP4, and TPX2.
  • 29. The method of claim 21, wherein the at least one gene selected from the group consisting of genes listed in Table 3B includes each of FLNC, GSN, GSTM2, TPM2, AZGP1, KLK2, FAM13C, and SRD5A2.
  • 30. The method of claim 21, wherein the at least one gene selected from the group consisting of genes listed in Table 3A includes each of BGN, COL1A1, SFRP4, and TPX2; and wherein the at least one gene selected from the group consisting of genes listed in Table 3B includes each of FLNC, GSN, GSTM2, TPM2, AZGP1, KLK2, FAM13C, and SRD5A2.
  • 31. The method of claim 21, wherein the at least one reference gene is a gene that does not exhibit a significantly different RNA expression level in cancerous prostate tissue compared to non-cancerous prostate tissue.
  • 32. The method of claim 21, wherein the at least one reference gene consists of from 1 to 6 reference genes.
  • 33. The method of claim 21, wherein the at least one reference gene comprises one or more of AAMP, ARF1, ATP5E, CLTC, EEF1A1, GPS1, GPX1, and PGK1.
  • 34. The method of claim 21, wherein the biological sample has a positive TMPRSS2 fusion status.
  • 35. The method of claim 21, wherein the biological sample has a negative TMPRSS2 fusion status.
  • 36. The method of claim 21, wherein the patient has early-stage prostate cancer.
  • 37. The method of claim 21, wherein the biological sample comprises prostate tumor tissue with the primary Gleason pattern for said prostate tumor.
  • 38. The method of claim 21, wherein the biological samples comprises prostate tumor tissue with the highest Gleason pattern for said prostate tumor.
  • 39. The method of claim 21, wherein the tissue sample comprises non-tumor prostate tissue.
  • 40. The method of claim 21, wherein the patient is receiving active surveillance treatment.
Parent Case Info

This application is a continuation of U.S. application Ser. No. 16/282,540, filed Feb. 22, 2019, which is a continuation of U.S. application Ser. No. 14/887,605, filed Oct. 20, 2015, now U.S. Pat. No. 10,260,104, issued Apr. 16, 2019, which is a continuation of U.S. application Ser. No. 13/190,391, filed Jul. 25, 2011, which claims the benefit of priority to U.S. Provisional Application Nos. 61/368,217, filed Jul. 27, 2010; 61/414,310, filed Nov. 16, 2010; and 61/485,536, filed May 12, 2011, all of which are hereby incorporated by reference.

Provisional Applications (3)
Number Date Country
61368217 Jul 2010 US
61414310 Nov 2010 US
61485536 May 2011 US
Continuations (3)
Number Date Country
Parent 16282540 Feb 2019 US
Child 16800292 US
Parent 14887605 Oct 2015 US
Child 16282540 US
Parent 13190391 Jul 2011 US
Child 14887605 US