Method for Using Gene Expression to Determine Prognosis of Prostate Cancer

Information

  • Patent Application
  • 20190249260
  • Publication Number
    20190249260
  • Date Filed
    February 22, 2019
    5 years ago
  • Date Published
    August 15, 2019
    4 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: N0: 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 N0M0 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 37-500 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 MasterPureTM 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 β-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 primary
For patients whose prostatectomy primary


Gleason pattern is also the highest Gleason
Gleason pattern is not the highest Gleason


pattern
pattern


Specimen 1 (A1) = primary Gleason pattern
Specimen 1 (B1) = highest Gleason pattern


Select and mark largest focus (greatest cross-
Select highest Gleason pattern tissue from


sectional area) of primary Gleason pattern
spatially distinct area from specimen B2, if


tissue. Invasive cancer area ≥ 5.0 mm.
possible. Invasive cancer area at least 5.0



mm if selecting secondary pattern, at least



2.2 mm if selecting Gleason pattern 5.


Specimen 2 (A2) = secondary Gleason pattern
Specimen 2 (B2) = primary Gleason pattern


Select and mark secondary Gleason pattern
Select largest focus (greatest cross-sectional


tissue from spatially distinct area from
area) of primary Gleason pattern tissue.


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









Table 3A
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


ST5
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


Table 4A
Primary
Highest
Primary
Highest


Official
Pattern
Pattern
Pattern
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


Table 4B
Primary
Highest
Primary
Highest


Official
Pattern
Pattern
Pattern
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


CSRP1
0.793
0.024
0.782
0.019


CTNNB1
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


DNM3
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


EIF2S3






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


NFKBIA
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


ST5
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







Gene 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


negatively associated with good prognosis)












cRFI
cRFI
bRFI
bRFI


Table 5A
Primary
Highest
Primary
Highest


Official
Pattern
Pattern
Pattern
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


MKI67
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


MYO6


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)












cRFI
cRFI
bRFI




Primary
Highest
Primary
bRFI


Table 5B
Pattern
Pattern
Pattern
Highest













Official
p-

p-

p-
Pattern















Symbol
HR
value
HR
value
HR
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


MPPED2
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)












cRFI
cRFI
bRFI




Primary
Highest
Primary
bRFI


Table 6A
Pattern
Pattern
Pattern
Highest













Official
p-

p-

p-
Pattern















Symbol
HR
value
HR
value
HR
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


MYO6


1.278
0.047


NETO2
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)












cRFI
cRFI
bRFI




Primary
Highest
Primary
bRFI


Table 6B
Pattern
Pattern
Pattern
Highest













Official
p-

p-

p-
Pattern















Symbol
HR
value
HR
value
HR
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


DNM3
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


EIF2S3






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


FAM49B
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


RASSF1
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


XRCC5
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)









Table 7A
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)









Table 7B
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


DNM3
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


KLF6
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


ST5
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)









Table 8A
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


ARHGDIB
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)









Table 8B
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


EPHB4


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


LAMA5


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












Table 9A







Official

Odds
Official

Odds


Symbol
p-value
Ratio
Symbol
p-value
Ratio















ABCC8
<.001
1.86
MAP3K5
<.001
2.06


ALDH18A1
0.005
1.49
MAP7
<.001
2.74


ALKBH3
0.043
1.30
MSH2
0.005
1.59


ALOX5
<.001
1.66
MSH3
0.006
1.45


AMPD3
<.001
3.92
MUC1
0.012
1.42


APEX1
<.001
2.00
MYO6
<.001
3.79


ARHGDIB
<.001
1.87
NCOR2
0.001
1.62


ASAP2
0.019
1.48
NDRG1
<.001
6.77


ATXN1
0.013
1.41
NETO2
<.001
2.63


BMPR1B
<.001
2.37
ODC1
<.001
1.98


CACNA1D
<.001
9.01
OR51E1
<.001
2.24


CADPS
0.015
1.39
PDE9A
<.001
2.21


CD276
0.003
2.25
PEX10
<.001
3.41


CDH1
0.016
1.37
PGK1
0.022
1.33


CDH7
<.001
2.22
PLA2G7
<.001
5.51


CDK7
0.025
1.43
PPP3CA
0.047
1.38


COL9A2
<.001
2.58
PSCA
0.013
1.43


CRISP3
<.001
2.60
PSMD13
0.004
1.51


CTNND1
0.033
1.48
PTCH1
0.022
1.38


ECE1
<.001
2.22
PTK2
0.014
1.38


EIF5
0.023
1.34
PTK6
<.001
2.29


EPHB4
0.005
1.51
PTK7
<.001
2.45


ERG
<.001
14.5
PTPRK
<.001
1.80


FAM171B
0.047
1.32
RAB30
0.001
1.60


FAM73A
0.008
1.45
REG4
0.018
1.58


FASN
0.004
1.50
RELA
0.001
1.62


GNPTAB
<.001
1.60
RFX1
0.020
1.43


GPS1
0.006
1.45
RGS10
<.001
1.71


GRB7
0.023
1.38
SCUBE2
0.009
1.48


HDAC1
<.001
4.95
SEPT9
<.001
3.91


HGD
<.001
1.64
SH3RF2
0.004
1.48


HIP1
<.001
1.90
SH3YL1
<.001
1.87


HNF1B
<.001
3.55
SHH
<.001
2.45


HSPA8
0.041
1.32
SIM2
<.001
1.74


IGF1R
0.001
1.73
SIPA1L1
0.021
1.35


ILF3
<.001
1.91
SLC22A3
<.001
1.63


IMMT
0.025
1.36
SLC44A1
<.001
1.65


ITPR1
<.001
2.72
SPINT1
0.017
1.39


ITPR3
<.001
5.91
TFDP1
0.005
1.75


JAG1
0.007
1.42
TMPRSS2ERGA
0.002
14E5


KCNN2
<.001
2.80
TMPRSS2ERGB
<.001
1.97


KHDRBS3
<.001
2.63
TRIM14
<.001
1.65


KIAA0247
0.019
1.38
TSTA3
0.018
1.38


KLK11
<.001
1.98
UAP1
0.046
1.39


LAMC1
0.008
1.56
UBE2G1
0.001
1.66


LAMC2
<.001
3.30
UGDH
<.001
2.22


LOX
0.009
1.41
XRCC5
<.001
1.66


LRP1
0.044
1.30
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)









Table 9B




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


ILIA
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)









Table 10A
cRFI
bRFI











Official 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)









Table 10B
cRFI
bRFI











Official 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











cRFI
bRFI
bRFI



Highest
Primary
Highest


Table 11
Pattern
Pattern
Pattern













Official 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)












Table 12A







Official


Official




Symbol
HR
p-value
Symbol
HR
p-value















AKR1C3
1.476
0.016
GREM1
1.942
<.001


ANLN
1.517
0.006
IFI30
1.482
0.048


APOC1
1.285
0.016
IGFBP3
1.513
0.027


APOE
1.490
0.024
INHBA
3.060
<.001


ASPN
3.055
<.001
KIF4A
1.355
0.001


ATP5E
1.788
0.012
KLK14
1.187
0.004


AURKB
1.439
0.008
LAPTM5
1.613
0.006


BGN
2.640
<.001
LTBP2
2.018
<.001


BIRC5
1.611
<.001
MMP11
1.869
<.001


BMP6
1.490
0.021
MYBL2
1.737
0.013


BRCA1
1.418
0.036
NEK2
1.445
0.028


CCNB1
1.497
0.021
NOX4
2.049
<.001


CD276
1.668
0.005
OLFML2B
1.497
0.023


CDC20
1.730
<.001
PLK1
1.603
0.006


CDH11
1.565
0.017
POSTN
2.585
<.001


CDH7
1.553
0.007
PPFIA3
1.502
0.012


CDKN2B
1.751
0.003
PTK6
1.527
0.009


CDKN2C
1.993
0.013
PTTG1
1.382
0.029


CDKN3
1.404
0.008
RAD51
1.304
0.031


CENPF
2.031
<.001
RGS7
1.251
<.001


CHAF1A
1.376
0.011
RRM2
1.515
<.001


CKS2
1.499
0.031
SAT1
1.607
0.004


COL1A1
2.574
<.001
SDC1
1.710
0.007


COL1A2
1.607
0.011
SESN3
1.399
0.045


COL3A1
2.382
<.001
SFRP4
2.384
<.001


COL4A1
1.970
<.001
SHMT2
1.949
0.003


COL5A2
1.938
0.002
SPARC
2.249
<.001


COL8A1
2.245
<.001
STMN1
1.748
0.021


CTHRC1
2.085
<.001
SULF1
1.803
0.004


CXCR4
1.783
0.007
THBS2
2.576
<.001


DDIT4
1.535
0.030
THY1
1.908
0.001


DYNLL1
1.719
0.001
TK1
1.394
0.004


F2R
2.169
<.001
TOP2A
2.119
<.001


FAM171B
1.430
0.044
TPX2
2.074
0.042


FAP
1.993
0.002
UBE2C
1.598
<.001


FCGR3A
2.099
<.001
UGT2B15
1.363
0.016


FN1
1.537
0.024
UHRF1
1.642
0.001


GPR68
1.520
0.018
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)












Table 12B







Official


Official




Symbol
HR
p-value
Symbol
HR
p-value















AAMP
0.649
0.040
IGFBP6
0.578
0.003


ABCA5
0.777
0.015
IL2
0.528
0.010


ABCG2
0.715
0.037
IL6ST
0.574
<.001


ACOX2
0.673
0.016
IL8
0.540
0.001


ADH5
0.522
<.001
ING5
0.688
0.015


ALDH1A2
0.561
<.001
ITGA6
0.710
0.005


AMACR
0.693
0.029
ITGA7
0.676
0.033


AMPD3
0.750
0.049
JUN
0.506
0.001


ANPEP
0.531
<.001
KIT
0.628
0.047


ATXN1
0.640
0.011
KLK1
0.523
0.002


AXIN2
0.657
0.002
KLK2
0.581
<.001


AZGP1
0.617
<.001
KLK3
0.676
<.001


BDKRB1
0.553
0.032
KRT15
0.684
0.005


BIN1
0.658
<.001
KRT18
0.536
<.001


BTRC
0.716
0.011
KRT5
0.673
0.004


C7
0.531
<.001
KRT8
0.613
0.006


CADM1
0.646
0.015
LAMB3
0.740
0.027


CASP7
0.538
0.029
LGALS3
0.678
0.007


CCNH
0.674
0.001
MGST1
0.640
0.002


CD164
0.606
<.001
MPPED2
0.629
<.001


CD44
0.687
0.016
MTSS1
0.705
0.041


CDK3
0.733
0.039
MYBPC1
0.534
<.001


CHN1
0.653
0.014
NCAPD3
0.519
<.001


COL6A1
0.681
0.015
NFAT5
0.536
<.001


CSF1
0.675
0.019
NRG1
0.467
0.007


CSRP1
0.711
0.007
OLFML3
0.646
0.001


CXCL12
0.650
0.015
OMD
0.630
0.006


CYP3A5
0.507
<.001
OR51E2
0.762
0.017


CYR61
0.569
0.007
PAGE4
0.518
<.001


DLGAP1
0.654
0.004
PCA3
0.581
<.001


DNM3
0.692
0.010
PGF
0.705
0.038


DPP4
0.544
<.001
PPAP2B
0.568
<.001


DPT
0.543
<.001
PPP1R12A
0.694
0.017


DUSP1
0.660
0.050
PRIMA1
0.678
0.014


DUSP6
0.699
0.033
PRKCA
0.632
0.001


EGR1
0.490
<.001
PRKCB
0.692
0.028


EGR3
0.561
<.001
PROM1
0.393
0.017


EIF5
0.720
0.035
PTEN
0.689
0.002


ERBB3
0.739
0.042
PTGS2
0.611
0.004


FAAH
0.636
0.010
PTH1R
0.629
0.031


FAM107A
0.541
<.001
RAB27A
0.721
0.046


FAM13C
0.526
<.001
RND3
0.678
0.029


FAS
0.689
0.030
RNF114
0.714
0.035


FGF10
0.657
0.024
SDHC
0.590
<.001


FKBP5
0.699
0.040
SERPINA3
0.710
0.050


FLNC
0.742
0.036
SH3RF2
0.570
0.005


FOS
0.556
0.005
SLC22A3
0.517
<.001


FOXQ1
0.666
0.007
SMAD4
0.528
<.001


GADD45B
0.554
0.002
SMO
0.751
0.026


GDF15
0.659
0.009
SRC
0.667
0.004


GHR
0.683
0.027
SRD5A2
0.488
<.001


GPM6B
0.666
0.005
STAT5B
0.700
0.040


GSN
0.646
0.006
SVIL
0.694
0.024


GSTM1
0.672
0.006
TFF3
0.701
0.045


GSTM2
0.514
<.001
TGFB1I1
0.670
0.029


HGD
0.771
0.039
TGFB2
0.646
0.010


HIRIP3
0.730
0.013
TNFRSF10B
0.685
0.014


HK1
0.778
0.048
TNFSF10
0.532
<.001


HLF
0.581
<.001
TPM2
0.623
0.005


HNF1B
0.643
0.013
TRO
0.767
0.049


HSD17B10
0.742
0.029
TUBB2A
0.613
0.003


IER3
0.717
0.049
VEGFB
0.780
0.034


IGF1
0.612
<.001
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))









Table 13A
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))









Table 13B
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






Pattern Tumor Tissue
416
106
36



Highest Gleason






Pattern Tumor Tissue
405
102
36



Normal Adjacent






Tissue
364
81
29










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 D R, 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



















95%
Max. Lower
RM-




q-valuea
Direction
Uncorrected
Confidence
Bound
Corrected


MicroRNA
p-value
(FDR)
of Associationb
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



















95%
Max. Lower
RM-




q-valuea
Direction
Uncorrected
Confidence
Bound
Corrected


MicroRNA
p-value
(FDR)
of Associationb
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







95%
Bound
RM-




q-valuea
Direction
Uncorrected
Confidence
@10%
Corrected


MicroRNA
p-value
(FDR)
of Associationb
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








Bound




q-valuea
Direction
Uncorrected
95% Confidence
@10%
RM-Corrected


MicroRNA
p-value
(FDR)
of Associationb
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







95%
Bound
RM-




q-valuea
Direction
Uncorrected
Confidence
@10%
Corrected


MicroRNA
p-value
(FDR)
of Associationb
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







95%
Bound
RM-




q-valuea
Direction
Uncorrected
Confidence
@10%
Corrected


MicroRNA
p-value
(FDR)
of Associationb
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







95%
Bound
RM-




q-valuea
Direction
Uncorrected
Confidence
@10%
Corrected


MicroRNA
p-value
(FDR)
of Associationb
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 Number of
Predictive of Clinical



MicroRNA-Gene
Recurrence at False


Tier
Pairs
Discovery Rate 10% (%)


















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
Forward
SEQ
Reverse
SEQ

SEQ



Official
Accession
ID
Primer
ID
Primer
ID
Probe
ID



Symbol:
Number:
NO
Sequence:
NO
Sequence:
NO
Sequence:
NO
Amplicon Sequence:







AAMP
NM_001087
   1
GTGTGGCAGG
   2
CTCCATCCAC
   3
CGCTTCAAAGGA
   4
GTGTGGCAGGTGGACACTAAGGAGGAGGTCTGGTCCTTTGAA





TGGACACTAA

TCCAGGTCTC

CCAGACCTCCTC

GCGGGAGACCTGGAGTGGATGGAG





ABCA5
NM_172232
   5
GGTATGGATC
   6
CAGCCCGCTT
   7
CACATGTGGCGA
   8
GGTATGGATCCCAAAGCCAAACAGCACATGTGGCGAGCAATT





CCAAAGCCA

TCTGTTTTTA

GCAATTCGAACT

CGAACTGCATTTAAAAACAGAAAGCGGGCTG





ABCB1
NM_000927
   9
AAACACCACT
  10
CAAGCCTGGA
  11
CAAGCCTGGAAC
  12
AAACACCACTGGAGCATTGACTACCAGGCTCGCCAATGATGCT





GGAGCATTGA

ACCTATAGCC

CTATAGCC

GCTCAAGTTAAAGGGGCTATAGGTTCCAGGCTTG





ABCC1
NM_004996
  13
TCATGGTGCC
  14
CGATTGTCTT
  15
ACCTGATACGTC
  16
TCATGGTGCCCGTCAATGCTGTGATGGCGATGAAGACCAAGA





CGTCAATG

TGCTCTTCAT

TTGGTCTTCATC

CGTATCAGGTGGCCCACATGAAGAGCAAAGACAATCG







GTG

GCCAT







ABCC3
NM_003786
  17
TCATCCTGGC
  18
CCGTTGAGTG
  19
TCTGTCCTGGCT
  20
TCATCCTGGCGATCTACTTCCTCTGGCAGAACCTAGGTCCCTC





GATCTACTTC

GAATCAGCAA

GGAGTCGCTTTC

TGTCCTGGCTGGAGTCGCTTTCATGGTCTTGCTGATTCCACTC





CT



AT

AACGG





ABCC4
NM_005845
  21
AGCGCCTGGA
  22
AGAGCCCCTG
  23
CGGAGTCCAGTG
  24
AGCGCCTGGAATCTACAACTCGGAGTCCAGTGTTTTCCCACTT





ATCTACAACT

GAGAGAAGAT

TTTTCCCACTTA

ATCATCTTCTCTCCAGGGGCTCT





ABCC8
NM_000352
  25
CGTCTGTCAC
  26
TGATCCGGTT
  27
AGTCTCTTGGCC
  28
CGTCTGTCACTGTGGAGTGGACAGGGCTGAAGGTGGCCAAGA





TGTGGAGTGG

TAGCAGGC

ACCTTCAGCCCT

GACTGCACCGCAGCCTGCTAAACCGGATCA





ABCG2
NM_004827
  29
GGTCTCAACG
  30
CTTGGATCTT
  31
ACGAAGATTTGC
  32
GGTCTCAACGCCATCCTGGGACCCACAGGTGGAGGCAAATCT





CCATCCTG

TCCTTGCAGC

CTCCACCTGTGG

TCGTTATTAGATGTCTTAGCTGCAAGGAAAGATCCAAG





ABHD2
NM_007011
  33
GTAGTGGGTC
  34
TGAGGGTTGG
  35
CAGGTGGCTCCT
  36
GTAGTGGGTCTGCATGGATGTTTCAGGGATCAAAGGAGCCAC





TGCATGGATG

CACTCAGG

TTGATCCCTGA

CTGGGCGCCTGAGTGCCAACCCTCA





T











ACE
NM_000789
  37
CCGCTGTACG
  38
CCGTGTCTGT
  39
TGCCCTCAGCAA
  40
CCGCTGTACGAGGATTTCACTGCCCTCAGCAATGAAGCCTACA





AGGATTTCA

GAAGCCGT

TGAAGCCTACAA

AGCAGGACGGCTTCACAGACACGG





ACOX2
NM_003500
  41
ATGGAGGTGC
  42
ACTCCGGGTA
  43
TGCTCTCAACTT
  44
ATGGAGGTGCCCAGAACACTGCACTCCGCAGGAAAGTTGAGA





CCAGAACAC

ACTGTGGATG

TCCTGCGGAGTG

GCATCATCCACAGTTACCCGGAGT





ACTR2
NM_005722
  45
ATCCGCATTG
  46
ATCCGCTAGA
  47
CCCGCAGAAAGC
  48
ATCCGCATTGAAGACCCACCCCGCAGAAAGCACATGGTATTCC





AAGACCCA

ACTGCACCAC

ACATGGTATTCC

TGGGTGGTGCAGTTCTAGCGGAT





ADAM15
NM_003815
  49
GGCGGGATGT
  50
ATTTCTGGGC
  51
TCAGCCACAATC
  52
GGCGGGATGTGGTAACAGAGACCAAGACTGTGGAGTTGGTGA





GGTAACAG

CTCCGAGT

ACCAACTCCACA

TTGTGGCTGATCACTCGGAGGCCCAGAAAT





ADAMTS1
NM_006988
  53
GGACAGGTGC
  54
ATCTACAACC
  55
CAAGCCAAAGGC
  56
GGACAGGTGCAAGCTCATCTGCCAAGCCAAAGGCATTGGCTA





AAGCTCATCT

TTGGGCTGCA

ATTGGCTACTTC

CTTCTTCGTTTTGCAGCCCAAGGTTGTAGAT





G

A

TTCG







ADH5
NM_000671
  57
ATGCTGTCAT
  58
CTGCTTCCTT
  59
TGTCTGCCCATT
  60
ATGCTGTCATCATTGTCACGGTTTGTCTGCCCATTATCTTCAT





CATTGTCACG

TCCCTTTCC

ATCTTCATTCTG

TCTGCAAGGGAAAGGGAAAGGAAGCAG









CAA







AFAP1
NM_198595
  61
GATGTCCATC
  62
CAACCCTGAT
  63
CCTCCAGTGCTG
  64
GATGTCCATCCTTGAAACAGCCTCTTCTGGGAACACAGCACTG





CTTGAAACAG

GCCTGGAG

TGTTCCCAGAAG

GAGGTCTCCAGGCATCAGGGTTG





C











AGTR1
NM_000685
  65
AGCATTGATC
  66
CTACAAGCAT
  67
ATTGTTCACCCA
  68
AGCATTGATCGATACCTGGCTATTGTTCACCCAATGAAGTCCC





GATACCTGGC

TGTGCGTCG

ATGAAGTCCCGC

GCCTTCGACGCACAATGCTTGTAG





AGTR2
NM_000686
  69
ACTGGCATAG
  70
ATTGACTGGG
  71
CCACCCAGACCC
  72
ACTGGCATAGGAAATGGTATCCAGAATGGAATTTTGCTACATG





GAAATGGTAT

TCTCTTTGCC

CATGTAGCAAAA

GGGTCTGGGTGGGGGCAAAGAGACCCAGTCAAT





CC











AIG1
NM_016108
  73
CGACGGTTCT
  74
TGCTCCTGCT
  75
AATCGAGATGAG
  76
CGACGGTTCTGCCCTTTATATTAATCGAGATGAGGACATCGCA





GCCCTTTAT

GGGATACTG

GACATCGCACCA

CCATCAGTATCCCAGCAGGAGCA





AKAP1
NM_003488
  77
TGTGGTTGGA
  78
GTCTACCCAC
  79
CTCCACCAGGGA
  80
TGTGGTTGGAGATGAAGTGGTGTTGATAAACCGGTCCCTGGTG





GATGAAGTGG

TGGGCAAGG

CCGGTTTATCAA

GAGCGAGGCCTTGCCCAGTGGGTAGAC





AKR1C1
BC040210
  81
GTGTGTGAAG
  82
CTCTGCAGGC
  83
CCAAATCCCAGG
  84
GTGTGTGAAGCTGAATGATGGTCACTTCATGCCTGTCCTGGGA





CTGAATGATG

GCATAGGT

ACAGGCATGAAG

TTTGGCACCTATGCGCCTGCAGAG





G











AKR1C3
NM_003739
  85
GCTTTGCCTG
  86
GTCCAGTCAC
  87
TGCGTCACCATC
  88
GCTTTGCCTGATGTCTACCAGAAGCCCTGTGTGTGGATGGTGA





ATGTCTACCA

CGGCATAGAG

CACACACAGGG

CGCAGAGGACGTCTCTATGCCGGTGACTGGAC





GAA

A









AKT1
NM_005163
  89
CGCTTCTATG
  90
TCCCGGTACA
  91
CAGCCCTGGACT
  92
CGCTTCTATGGCGCTGAGATTGTGTCAGCCCTGGACTACCTGC





GCGCTGAGAT

CCACGTTCTT

ACCTGCACTCGG

ACTCGGAGAAGAACGTGGTGTACCGGGA





AKT2
NM_001626
  93
TCCTGCCACC
  94
GGCGGTAAAT
  95
CAGGTCACGTCC
  96
TCCTGCCACCCTTCAAACCTCAGGTCACGTCCGAGGTCGACA





CTTCAAACC

TCATCATCGA

GAGGTCGACACA

CAAGGTACTTCGATGATGAATTTACCGCC







A









AKT3
NM_005465
  97
TTGTCTCTGC
  98
CCAGCATTAG
  99
TCACGGTACACA
 100
TTGTCTCTGCCTTGGACTATCTACATTCCGGAAAGATTGTGTA





CTTGGACTAT

ATTCTCCAAC

ATCTTTCCGGA

CCGTGATCTCAAGTTGGAGAATCTAATGCTGG





CTACA

TTGA









ALCAM
NM_001627
 101
GAGGAATATG
 102
GTGGCGGAGA
 103
CCAGTTCCTGCC
 104
GAGGAATATGGAATCCAAGGGGGCCAGTTCCTGCCGTCTGCT





GAATCCAAGG

TCAAGAGG

GTCTGCTCTTCT

CTTCTGCCTCTTGATCTCCGCCAC





G











ALDH18A1
NM_002860
 105
GATGCAGCTG
 106
CTCCAGCTCA
 107
CCTGAAACTTGC
 108
GATGCAGCTGGAACCCAAGCTGCAGCAGGAGATGCAAGTTTC





GAACCCAA

GTGGGGAA

ATCTCCTGCTGC

AGGATGTTCCCCACTGAGCTGGAG





ALDH1A2
NM_170696
 109
CACGTCTGTC
 110
GACCGTGGCT
 111
TCTCTGTAGGGC
 112
CACGTCTGTCCCTCTCTGCTTTCTCTGTAGGGCCCAGCTCTCA





CCTCTCTGCT

CAACTTTGTA

CCAGCTCTCAGG

GGAATACAAAGTTGAGCCACGGTC







T









ALKBH3
NM_139178
 113
TCGCTTAGTC
 114
TCTGAGCCCC
 115
TAAACAGGGCAG
 116
TCGCTTAGTCTGCACCTCAACCGTGCGGAAAGTGACTGCCCTG





TGCACCTCAA

AGTTTTTCC

TCACTTTCCGCA

TTTACTGAGGAAAAACTGGGGCTCAGA





C











ALOX12
NM_000697
 117
AGTTCCTCAA
 118
AGCACTAGCC
 119
CATGCTGTTGAG
 120
AGTTCCTCAATGGTGCCAACCCCATGCTGTTGAGACGCTCGAC





TGGTGCCAAC

TGGAGGGC

ACGCTCGACCTC

CTCTCTGCCCTCCAGGCTAGTGCT





ALOX5
NM_000698
 121
GAGCTGCAGG
 122
GAAGCCTGAG
 123
CCGCATGCCGTA
 124
GAGCTGCAGGACTTCGTGAACGATGTCTACGTGTACGGCATG





ACTTCGTGA

GACTTGCG

CACGTAGACATC

CGGGGCCGCAAGTCCTCAGGCTTC





AMACR
NM_203382
 125
GTCTCTGGGC
 126
TGGGTATAAG
 127
TCCATGTGTTTG
 128
GTCTCTGGGCTGTCAGCTTTCCTTTCTCCATGTGTTTGATTTC





TGTCAGCTTT

ATCCAGAACT

ATTTCTCCTCAG

TCCTCAGGCTGGTAGCAAGTTCTGGATCTTATACCCA







TGC

GC







AMPD3
NM_000480
 129
TGGTTCATCC
 130
CATAAATCCG
 131
TACTCTCCCAAC
 132
TGGTTCATCCAGCACAAGGTCTACTCTCCCAACATGCGCTGGA





AGCACAAGG

GGGCACCT

ATGCGCTGGATC

TCATCCAGGTGCCCCGGATTTATG





ANGPT2
NM_001147
 133
CCGTGAAAGC
 134
TTGCAGTGGG
 135
AAGCTGACACAG
 136
CCGTGAAAGCTGCTCTGTAAAAGCTGACACAGCCCTCCCAAGT





TGCTCTGTAA

AAGAACAGTC

CCCTCCCAAGTG

GAGCAGGACTGTTCTTCCCACTGCAA





ANLN
NM_018685
 137
TGAAAGTCCA
 138
CAGAACCAAG
 139
CCAAAGAACTCG
 140
TGAAAGTCCAAAACCAGGAAAATTCCAAAGAACTCGTGTCCCT





AAACCAGGAA

GCTATCACCA

TGTCCCTCGAGC

CGAGCTGAATCTGGTGATAGCCTTGGTTCTG





ANPEP
NM_001150
 141
CCACCTTGGA
 142
TCTCAGCGTC
 143
CTCCCCAACACG
 144
CCACCTTGGACCAAAGTAAAGCGTGGAATCGTTACCGCCTCCC





CCAAAGTAAA

ACCTGGTAGG

CTGAAACCCG

CAACACGCTGAAACCCGATTCCTACCGGGTGACGCTGAGA





GC

A









ANXA2
NM_004039
 145
CAAGACACTA
 146
CGTGTCGGGC
 147
CCACCACACAGG
 148
CAAGACACTAAGGGCGACTACCAGAAAGCGCTGCTGTACCTG





AGGGCGACTA

TTCAGTCAT

TACAGCAGCGCT

TGTGGTGGAGATGACTGAAGCCCGACACG





CCA











APC
NM_000038
 149
GGACAGCAGG
 150
ACCCACTCGA
 151
CATTGGCTCCCC
 152
GGACAGCAGGAATGTGTTTCTCCATACAGGTCACGGGGAGCC





AATGTGTTTC

TTTGTTTCTG

GTGACCTGTA

AATGGTTCAGAAACAAATCGAGTGGGT





APEX1
NM_001641
 153
GATGAAGCCT
 154
AGGTCTCCAC
 155
CTTTCGGGAAGC
 156
GATGAAGCCTTTCGCAAGTTCCTGAAGGGCCTGGCTTCCCGAA





TTCGCAAGTT

ACAGCACAAG

CAGGCCCTT

AGCCCCTTGTGCTGTGTGGAGACCT





APOC1
NM_001645
 157
CCAGCCTGAT
 158
CACTCTGAAT
 159
AGGACAGGACCT
 160
CCAGCCTGATAAAGGTCCTGCGGGCAGGACAGGACCTCCCAA





AAAGGTCCTG

CCTTGCTGGA

CCCAACCAAGC

CCAAGCCCTCCAGCAAGGATTCAGAGTG





APOE
NM_000041
 161
GCCTCAAGAG
 162
CCTGCACCTT
 163
ACTGGCGCTGCA
 164
GCCTCAAGAGCTGGTTCGAGCCCCTGGTGGAAGACATGCAGC





CTGGTTCG

CTCCACCA

TGTCTTCCAC

GCCAGTGGGCCGGGCTGGTGGAGAAGGTGCAGG





APRT
NM_000485
 165
GAGGTCCTGG
 166
AGGTGCCAGC
 167
CCTTAAGCGAGG
 168
GAGGTCCTGGAGTGCGTGAGCCTGGTGGAGCTGACCTCGCTT





AGTGCGTG

TTCTCCCT

TCAGCTCCACCA

AAGGGCAGGGAGAAGCTGGCACCT





AQP2
NM_000486
 169
GTGTGGGTGC
 170
CCCTTCAGCC
 171
CTCCTTCCCTTC
 172
GTGTGGGTGCCAGTCCTCCTCAGGAGAAGGGGAAGGGAAGG





CAGTCCTC

CTCTCAAAG

CCCTTCTCCTGA

AGGCCACTTTGAGAGGGCTGAAGGG





AR
NM_000044
 173
CGACTTCACC
 174
TGACACAAGT
 175
ACCATGCCGCCA
 176
CGACTTCACCGCACCTGATGTGTGGTACCCTGGCGGCATGGT





GCACCTGAT

GGGACTGGGA

GGGTACCACA

GAGCAGAGTGCCCTATCCCAGTCCCACTTGTGTCA







TA









ARF1
NM_001658
 177
CAGTAGAGAT
 178
ACAAGCACAT
 179
CTTGTCCTTGGG
 180
CAGTAGAGATCCCCGCAACTCGCTTGTCCTTGGGTCACCCTGC





CCCCGCAACT

GGCTATGGAA

TCACCCTGCA

ATTCCATAGCCATGTGCTTGT





ARHGAP29
NM_004815
 181
CACGGTCTCG
 182
CAGTTGCTTG
 183
ATGCCAGACCCA
 184
CACGGTCTCGTGGTGAAGTCAATGCCAGACCCAGACAAAGCA





TGGTGAAGT

CCCAGGAC

GACAAAGCATCA

TCAGCTTGTCCTGGGCAAGCAACTG





ARHGDIB
NM_001175
 185
TGGTCCCTAG
 186
TGATGGAGGA
 187
TAAAACCGGGCT
 188
TGGTCCCTAGAACAAGAGGCTTAAAACCGGGCTTTCACCCAAC





AACAAGAGGC

TCAGAGGGAG

TTCACCCAACCT

CTGCTCCCTCTGATCCTCCATCA





ASAP2
NM_003887
 189
CGGCCCATCA
 190
CTCTGGCCAA
 191
CTGGGCTCCAAC
 192
CGGCCCATCAGCTTCTACCAGCTGGGCTCCAACCAGCTTCAG





GCTTCTAC

AGATACAGCG

CAGCTTCAGTCT

TCTAACGCTGTATCTTTGGCCAGAG





ASPN
NM_017680
 193
TGGACTAATC
 194
AAACACCCTT
 195
AGTATCACCCAG
 196
TGGACTAATCTGTGGGAGCAGTTTATTCCAGTATCACCCAGGG





TGTGGGAGCA

CAACACAGTC

GGTGCAGCCAC

TGCAGCCACACCAGGACTGTGTTGAAGGGTGTTT







C









ATM
NM_000051
 197
TGCTTTCTAC
 198
GTTGTGGATC
 199
CCAGCTGTCTTC
 200
TGCTTTCTACACATGTTCAGGGATTTTTCACCAGCTGTCTTCG





ACATGTTCAG

GGCTCGTT

GACACTTCTCGC

ACACTTCTCGCAAACGAGCCGATCCACAAC





GG











ATP5E
NM_006886
 201
CCGCTTTCGC
 202
TGGGAGTATC
 203
TCCAGCCTGTCT
 204
CCGCTTTCGCTACAGCATGGTGGCCTACTGGAGACAGGCTGG





TACAGCAT

GGATGTAGCT

CCAGTAGGCCAC

ACTCAGCTACATCCGATACTCCCA







G









ATP5J
NM_
 205
GTCGACCGAC
 206
CTCTACTTCC
 207
CTACCCGCCATC
 208
GTCGACCGACTGAAACGGCGGCCCATAATGCATTGCGATGGC



001003703

TGAAACGG

GGCCCTGG

GCAATGCATTAT

GGGTAGGCGTGTGGGGGCGGAGCCAGGGCCGGAAGTAGAG





ATXN1
NM_000332
 209
GATCGACTCC
 210
GAACTGTAT
 211
CGGGCTATGGCT
 212
GATCGACTCCAGCACCGTAGAGAGGATTGAAGACAGCCATAG





AGCACCGTAG

CACGGCCACG

GTCTTCAATCCT

CCCGGGCGTGGCCGTGATACAGTTC





AURKA
NM_003600
 213
CATCTTCCAG
 214
TCCGACCTTC
 215
CTCTGTGGCACC
 216
CATCTTCCAGGAGGACCACTCTCTGTGGCACCCTGGACTACCT





GAGGACCACT

AATCATTTCA

CTGGACTACCTG

GCCCCCTGAAATGATTGAAGGTCGGA





AURKB
NM_004217
 217
AGCTGCAGAA
 218
GCATCTGCCA
 219
TGACGAGCAGCG
 220
AGCTGCAGAAGAGCTGCACATTTGACGAGCAGCGAACAGCCA





GAGCTGCACA

ACTCCTCCAT

AACAGCCACG

CGATCATGGAGGAGTTGGCAGATGC





T











AXIN2
NM_004655
 221
GGCTATGTCT
 222
ATCCGTCAGC
 223
ACCAGCGCCAAC
 224
GGCTATGTCTTTGCACCAGCCACCAGCGCCAACGACAGTGAG





TTGCACCAGC

GCATCACT

GACAGTGAGATA

ATATCCAGTGATGCGCTGACGGAT





AZGP1
NM_001185
 225
GAGGCCAGCT
 226
CAGGAAGGGC
 227
TCTGAGATCCCA
 228
GAGGCCAGCTAGGAAGCAAGGGTTGGAGGCAATGTGGGATCT





AGGAAGCAA

AGCTACTGG

CATTGCCTCCAA

CAGACCCAGTAGCTGCCCTTCCTG





BAD
NM_032989
 229
GGGTCAGGGG
 230
CTGCTCACTC
 231
TGGGCCCAGAGC
 232
GGGTCAGGGGCCTCGAGATCGGGCTTGGGCCCAGAGCATGTT





CCTCGAGAT

GGCTCAAACT

ATGTTCCAGATC

CCAGATCCCAGAGTTTGAGCCGAGTGAGCAG







C









BAG5
NM_
 233
ACTCCTGCAA
 234
ACAAACAGCT
 235
ACACCGGATTTA
 236
ACTCCTGCAATGAACCCTGTTGACACCGGATTTAGCTCTTGTC



001015049

TGAACCCTGT

CCCCACGA

GCTCTTGTCGGC

GGCCTTCGTGGGGAGCTGTTTGT





BAK1
NM_001188
 237
CCATTCCCAC
 238
GGGAACATAG
 239
ACACCCCAGACG
 240
CCATTCCCACCATTCTACCTGAGGCCAGGACGTCTGGGGTGT





CATTCTACCT

ACCCACCAAT

TCCTGGCCT

GGGGATTGGTGGGTCTATGTTCCC





BAX
NM_004324
 241
CCGCCGTGGA
 242
TTGCCGTCAG
 243
TGCCACTCGGAA
 244
CCGCCGTGGACACAGACTCCCCCCGAGAGGTCTTTTTCCGAG





CACAGACT

AAAACATGTC

AAAGACCTCTCG

TGGCAGCTGACATGTTTTCTGACGGCAA







A

G







BBC3
NM_014417
 245
CCTGGAGGGT
 246
CTAATTGGGC
 247
CATCATGGGACT
 248
CCTGGAGGGTCCTGTACAATCTCATCATGGGACTCCTGCCCTT





CCTGTACAAT

TCCATCTCG

CCTGCCCTTACC

ACCCAGGGGCCACAGAGCCCCCGAGATGGAGCCCAATTAG





BCL2
NM_000633
 249
CAGATGGACC
 250
CCTATGATTT
 251
TTCCACGCCGAA
 252
CAGATGGACCTAGTACCCACTGAGATTTCCACGCCGAAGGAC





TAGTACCCAC

AAGGGCATTT

GGACAGCGAT

AGCGATGGGAAAAATGCCCTTAAATCATAGG





TGAGA

TTCC









BDKRB1
NM_000710
 253
GTGGCAGAAA
 254
GAAGGGCAAG
 255
ACCTGGCAGCCT
 256
GTGGCAGAAATCTACCTGGCCAACCTGGCAGCCTCTGATCTG





TCTACCTGGC

CCCAAGAC

CTGATCTGGTGT

GTGTTTGTCTTGGGCTTGCCCTTC





BGN
NM_001711
 257
GAGCTCCGCA
 258
CTTGTTGTTC
 259
CAAGGGTCTCCA
 260
GAGCTCCGCAAGGATGACTTCAAGGGTCTCCAGCACCTCTAC





AGGATGAC

ACCAGGACGA

GCACCTCTACGC

GCCCTCGTCCTGGTGAACAACAAG





BIK
NM_001197
 261
ATTCCTATGG
 262
GGCAGGAGTG
 263
CCGGTTAACTGT
 264
ATTCCTATGGCTCTGCAATTGTCACCGGTTAACTGTGGCCTGT





CTCTGCAATT

AATGGCTCTT

GGCCTGTGCCC

GCCCAGGAAGAGCCATTCACTCCTGCC





GTC

C









BIN1
NM_004305
 265
CCTGCAAAAG
 266
CGTGGTTGAC
 267
CTTCGCCTCCAG
 268
CCTGCAAAAGGGAACAAGAGCCCTTCGCCTCCAGATGGCTCC





GGAACAAGAG

TCTGATCTCG

ATGGCTCCC

CCTGCCGCCACCCCCGAGATCAGAGTCAACCACG





BIRC5
NM_
 269
TTCAGGTGGA
 270
CACACAGCAG
 271
TCTGCCAGACGC
 272
TTCAGGTGGATGAGGAGACAGAATAGAGTGATAGGAAGCGTC



001012271

TGAGGAGACA

TGGCAAAAG

TTCCTATCACTC

TGGCAGATACTCCTTTTGCCACTGCTGTGTG









TATTC







BMP6
NM_001718
 273
GTGCAGACCT
 274
CTTAGTTGGC
 275
TGAACCCCGAGT
 276
GTGCAGACCTTGGTTCACCTTATGAACCCCGAGTATGTCCCCA





TGGTTCACCT

GCACAGCAC

ATGTCCCCAAAC

AACCGTGCTGTGCGCCAACTAAG





BMPR1B
NM_001203
 277
ACCACTTTGG
 278
GCGGTGTTTG
 279
ATTCACATTACC
 280
ACCACTTTGGCCATCCCTGCATTTGGGGCCGCTATGGTAATGT





CCATCCCT

TACCCAGTG

ATAGCGGCCCCA

GAATGCACTGGGTACAAACACCGC





BRCA1
NM_007294
 281
TCAGGGGGCT
 282
CCATTCCAGT
 283
CTATGGGCCCTT
 284
TCAGGGGGCTAGAAATCTGTTGCTATGGGCCCTTCACCAACAT





AGAAATCTGT

TGATCTGTGG

CACCAACATGC

GCCCACAGATCAACTGGAATGG





BRCA2
NM_000059
 285
AGTTCGTGCT
 286
AAGGTAAGCT
 287
CATTCTTCACTG
 288
AGTTCGTGCTTTGCAAGATGGTGCAGAGCTTTATGAAGCAGTG





TTGCAAGATG

GGGTCTGCTG

CTTCATAAAGCT

AAGAATGCAGCAGACCCAGCTTACCTT









CTGCA







BTG1
NM_001731
 289
GAGGTCCGAG
 290
AGTTATTTTC
 291
CGCTCGTCTCTT
 292
GAGGTCCGAGCGATGTGACCAGGCCGCCATCGCTCGTCTCTT





CGATGTGA

GAGACAGGAG

CCTCTCTCCTGC

CCTCTCTCCTGCCGCCTCCTGTCTCGAAAATAACT







GC









BTG3
NM_006806
 293
CCATATCGCC
 294
CCAGTGATTC
 295
CATGGGTACCTC
 296
CCATATCGCCCAATTCCAGTGACATGGGTACCTCCTCCTGGAA





CAATTCCA

CGGTCACAA

CTCCTGGAATGC

TGCATTGTGACCGGAATCACTGG





BTRC
NM_033637
 297
GTTGGGACAC
 298
TGAAGCAGTC
 299
CAGTCGGCCCAG
 300
GTTGGGACACAGTTGGTCTGCAGTCGGCCCAGGACGGTCTAC





AGTTGGTCTG

AGTTGTGCTG

GACGGTCTACT

TCAGCACAACTGACTGCTTCA





BUB1
NM_004336
 301
CCGAGGTTAA
 302
AAGACATGGC
 303
TGCTGGGAGCCT
 304
CCGAGGTTAATCCAGCACGTATGGGGCCAAGTGTAGGCTCCC





TCCAGCACGT

GCTCTCAGTT

ACACTTGGCCC

AGCAGGAACTGAGAGCGCCATGTCTT





A

C









C7
NM_000587
 305
ATGTCTGAGT
 306
AGGCCTTATG
 307
ATGCTCTGCCCT
 308
ATGTCTGAGTGTGAGGCGGGCGCTCTGAGATGCAGAGGGCAG





GTGAGGCGG

CTGGTGACAG

CTGCATCTCAGA

AGCATCTCTGTCACCAGCATAAGGCCT





CACNA1D
NM_000720
 309
AGGACCCAGC
 310
CCTACATTCC
 311
CAGTACACTGGC
 312
AGGACCCAGCTCCATGTGCGTTCTCAGGGAATGGACGCCAGT





TCCATGTG

GTGCCATTG

GTCCATTCCCTG

GTACTGCCAATGGCACGGAATGTAGG





CADM1
NM_014333
 313
CCACCACCAT
 314
GATCCACTGC
 315
TCTTCACCTGCT
 316
CCACCACCATCCTTACCATCATCACAGATTCCCGAGCAGGTGA





CCTTACCATC

CCTGATCG

CGGGAATCTGTG

AGAAGGCTCGATCAGGGCAGTGGATC





CADPS
NM_003716
 317
CAGCAAGGAG
 318
GGTCCTCTTC
 319
CTCCTGGATGGC
 320
CAGCAAGGAGACTGTGCTGAGCTCCTGGATGGCCAAATTTGAT





ACTGTGCTGA

TCCACGGTAG

CAAATTTGATGC

GCCATCTACCGTGGAGAAGAGGACC







AT









CASP1
NM_001223
 321
AACTGGAGCT
 322
CATCTACGCT
 323
TCACAGGCATGA
 324
AACTGGAGCTGAGGTTGACATCACAGGCATGACAATGCTGCTA





GAGGTTGACA

GTACCCCAGA

CAATGCTGCTAC

CAAAATCTGGGGTACAGCGTAGATG









A







CASP3
NM_032991
 325
TGAGCCTGAG
 326
CCTTCCTGCG
 327
TCAGCCTGTTCC
 328
TGAGCCTGAGCAGAGACATGACTCAGCCTGTTCCATGAAGGC





CAGAGACATG

TGGTCCAT

ATGAAGGCAGAG

AGAGCCATGGACCACGCAGGAAGG





A



C







CASP7
NM_033338
 329
GCAGCGCCGA
 330
AGTCTCTCTC
 331
CTTTCGCTAAAG
 332
GCAGCGCCGAGACTTTTAGTTTCGCTTTCGCTAAAGGGGCCCC





GACTTTTA

CGTCGCTCC

GGGCCCCAGAC

AGACCCTTGCTGCGGAGCGACGGAGAGAGACT





CAV1
NM_001753
 333
GTGGCTCAAC
 334
CAATGGCCTC
 335
ATTTCAGCTGAT
 336
GTGGCTCAACATTGTGTTCCCATTTCAGCTGATCAGTGGGCCT





ATTGTGTTCC

CATTTTACAG

CAGTGGGCCTCC

CCAAGGAGGGGCTGTAAAATGGAGGCCATTG





CAV2
NM_198212
 337
CTTCCCTGGG
 338
CTCCTGGTCA
 339
CCCGTACTGTCA
 340
CTTCCCTGGGACGACTTGCCAGCTCTGAGGCATGACAGTACG





ACGACTTG

CCCTTCTGG

TGCCTCAGAGCT

GGCCCCCAGAAGGGTGACCAGGAG





CCL2
NM_002982
 341
CGCTCAGCCA
 342
GCACTGAGAT
 343
TGCCCCAGTCAC
 344
CGCTCAGCCAGATGCAATCAATGCCCCAGTCACCTGCTGTTAT





GATGCAATC

CTTCCTATTG

CTGCTGTTA

AACTTCACCAATAGGAAGATCTCAGTGC







GTGAA









CCL5
NM_002985
 345
AGGTTCTGAG
 346
ATGCTGACTT
 347
ACAGAGCCCTGG
 348
AGGTTCTGAGCTCTGGCTTTGCCTTGGCTTTGCCAGGGCTCTG





CTCTGGCTTT

CCTTCCTGGT

CAAAGCCAAG

TGACCAGGAAGGAAGTCAGCAT





CCNB1
NM_031966
 349
TTCAGGTTGT
 350
CATCTTCTTG
 351
TGTCTCCATTAT
 352
TTCAGGTTGTTGCAGGAGACCATGTACATGACTGTCTCCATTA





TGCAGGAGAC

GGCACACAAT

TGATCGGTTCAT

TTGATCGGTTCATGCAGAATAATTGTGTGCCCAAGAAGATG









GCA







CCND1
NM_001758
 353
GCATGTTCGT
 354
CGGTGTAGAT
 355
AAGGAGACCATC
 356
GCATGTTCGTGGCCTCTAAGATGAAGGAGACCATCCCCCTGA





GGCCTCTAAG

GCACAGCTTC

CCCCTGACGGC

CGGCCGAGAAGCTGTGCATCTACACCG





A

TC









CCNE2
NM_057749
 357
ATGCTGTGGC
 358
ACCCAAATTG
 359
TACCAAGCAACC
 360
ATGCTGTGGCTCCTTCCTAACTGGGGCTTTCTTGACATGTAGG





TCCTTCCTAA

TGATATACAA

TACATGTCAAGA

TTGCTTGGTAATAACCTTTTTGTATATCACAATTTGGGT





CT

AAAGGTT

AAGCCC







CCNH
NM_001239
 361
GAGATCTTCG
 362
CTGCAGACGA
 363
CATCAGCGTCCT
 364
GAGATCTTCGGTGGGGGTACGGGTGTTTTACGCCAGGACGCT





GTGGGGGTA

GAACCCAAAC

GGCGTAAAACAC

GATGCGTTTGGGTTCTCGTCTGCAG





CCR1
NM_001295
 365
TCCAAGACCC
 366
TCGTAGGCTT
 367
ACTCACCACACC
 368
TCCAAGACCCAATGGGAATTCACTCACCACACCTGCAGCCTTC





AATGGGAA

TCGTGAGGA

TGCAGCCTTCAC

ACTTTCCTCACGAAAGCCTACGA





CD164
NM_006016
 369
CAACCTGTGC
 370
ACACCCAAGA
 371
CCTCCAATGAAA
 372
CAACCTGTGCGAAAGTCTACCTTTGATGCAGCCAGTTTCATTG





GAAAGTCTAC

CCAGGACAAT

CTGGCTGCATCA

GAGGAATTGTCCTGGTCTTGGGTGT





C











CD1A
NM_001763
 373
GGAGTGGAAG
 374
TCATGGGCGT
 375
CGCACCATTCGG
 376
GGAGTGGAAGGAACTGGAAACATTATTCCGTATACGCACCATT





GAACTGGAAA

ATCTACGAAT

TCATTTGAGG

CGGTCATTTGAGGGAATTCGTAGATACGCCCATGA





CD276
NM_
 377
CCAAAGGATG
 378
GGATGACTTG
 379
CCACTGTGCAGC
 380
CCAAAGGATGCGATACACAGACCACTGTGCAGCCTTATTTCTC



001024736

CGATACACAG

GGAATCATGT

CTTATTTCTCCA

CAATGGACATGATTCCCAAGTCATCC







C

ATG







CD44
NM_000610
 381
GGCACCACTG
 382
GATGCTCATG
 383
ACTGGAACCCAG
 384
GGCACCACTGCTTATGAAGGAAACTGGAACCCAGAAGCACAC





CTTATGAAGG

GTGAATGAGG

AAGCACACCCTC

CCTCCCCTCATTCACCATGAGCATC





CD68
NM_001251
 385
TGGTTCCCAG
 386
CTCCTCCACC
 387
CTCCAAGCCCAG
 388
TGGTTCCCAGCCCTGTGTCCACCTCCAAGCCCAGATTCAGATT





CCCTGTGT

CTGGGTTGT

ATTCAGATTCGA

CGAGTCATGTACACAACCCAGGGTGGAGGAG









GTCA







CD82
NM_002231
 389
GTGCAGGCTC
 390
GACCTCAGGG
 391
TCAGCTTCTACA
 392
GTGCAGGCTCAGGTGAAGTGCTGCGGCTGGGTCAGCTTCTAC





AGGTGAAGTG

CGATTCATGA

ACTGGACAGACA

AACTGGACAGACAACGCTGAGCTCATGAATCGCCCTGAGGTC









ACGCTG







CDC20
NM_001255
 393
TGGATTGGAG
 394
GCTTGCACTC
 395
ACTGGCCGTGGC
 396
TGGATTGGAGTTCTGGGAATGTACTGGCCGTGGCACTGGACA





TTCTGGGAAT

CACAGGTACA

ACTGGACAACA

ACAGTGTGTACCTGTGGAGTGCAAGC





G

CA









CDC25B
NM_021873
 397
GCTGCAGGAC
 398
TAGGGCAGCT
 399
CTGCTACCTCCC
 400
GCTGCAGGACCAGTGAGGGGCCTGCGCCAGTCCTGCTACCTC





CAGTGAGG

GGCTTCAG

TTGCCTTTCGAG

CCTTGCCTTTCGAGGCCTGAAGCCAGCTGCCCTA





CDC6
NM_001254
 401
GCAACACTCC
 402
TGAGGGGGAC
 403
TTGTTCTCCACC
 404
GCAACACTCCCCATTTACCTCCTTGTTCTCCACCAAAGCAAGG





CCATTTACCT

CATTCTCTTT

AAAGCAAGGCAA

CAAGAAAGAGAATGGTCCCCCTCA





C











CDH1
NM_004360
 405
TGAGTGTCCC
 406
CAGCCGCTTT
 407
TGCCAATCCCGA
 408
TGAGTGTCCCCCGGTATCTTCCCCGCCCTGCCAATCCCGATGA





CCGGTATCTT

CAGATTTTCA

TGAAATTGGAAA

AATTGGAAATTTTATTGATGAAAATCTGAAAGCGGCTG





C

T

TTT







CDH10
NM_006727
 409
TGTGGTGCAA
 410
TGTAAATGAC
 411
ATGCCGATGACC
 412
TGTGGTGCAAGTCACAGCTACAGATGCCGATGACCCTTCATAT





GTCACAGCTA

TCTGGCGCTG

CTTCATATGGGA

GGGAACAGCGCCAGAGTCATTTACA





C











CDH11
NM_001797
 413
GTCGGCAGAA
 414
CTACTCATGG
 415
CCTTCTGCCCAT
 416
GTCGGCAGAAGCAGGACTTGTACCTTCTGCCCATAGTGATCAG





GCAGGACT

GCGGGATG

AGTGATCAGCGA

CGATGGCGGCATCCCGCCCATGAGTAG





CDH19
NM_021153
 417
AGTACCATAA
 418
AGACTGCCTG
 419
ACTCGGAAAACC
 420
AGTACCATAATGCGGGAACGCAAGACTCGGAAAACCACAAGC





TGCGGGAACG

TATAGGCTCC

ACAAGCGCTGAG

GCTGAGATCAGGAGCCTATACAGGCAGTCT







TG









CDH5
NM_001795
 421
ACAGGAGACG
 422
CAGCAGTGAG
 423
TATTCTCCCGGT
 424
ACAGGAGACGTGTTCGCCATTGAGAGGCTGGACCGGGAGAAT





TGTTCGCC

GTGGTACTCT

CCAGCCTCTCAA

ATCTCAGAGTACCACCTCACTGCTG







GA









CDH7
NM_033646
 425
GTTTGACATG
 426
AGTCACATCC
 427
ACCTCAACGTCA
 428
GTTTGACATGGCTGCACTGAGAAACCTCAACGTCATCCGAGAC





GCTGCACTGA

CTCCGGGT

TCCGAGACACCA

ACCAAGACCCGGAGGGATGTGACT





CDK14
NM_012395
 429
GCAAGGTAAA
 430
GATAGCTGTG
 431
CTTCCTGCAGCC
 432
GCAAGGTAAATGGGAAGTTGGTAGCTCTGAAGGTGATCAGGC





TGGGAAGTTG

AAAGGTGTCC

TGATCACCTTCA

TGCAGGAAGAAGAAGGGACACCTTTCACAGCTATC





G

CT









CDK2
NM_001798
 433
AATGCTGCAC
 434
TTGGTCACAT
 435
CCTTGGCCGAAA
 436
AATGCTGCACTACGACCCTAACAAGCGGATTTCGGCCAAGGC





TACGACCCTA

CCTGGAAGAA

TCCGCTTGT

AGCCCTGGCTCACCCTTTCTTCCAGGATGTGACCAA





CDK3
NM_001258
 437
CCAGGAAGGG
 438
GTTGCATGAG
 439
CTCTGGCTCCAG
 440
CCAGGAAGGGACTGGAAGAGATTGTGCCCAATCTGGAGCCAG





ACTGGAAGA

CAGGTCCC

ATTGGGCACAAT

AGGGCAGGGACCTGCTCATGCAAC





CDK7
NM_001799
 441
GTCTCGGGCA
 442
CTCTGGCCTT
 443
CCTCCCCAAGGA
 444
GTCTCGGGCAAAGCGTTATGAGAAGCTGGACTTCCTTGGGGA





AAGCGTTAT

GTAAACGGTG

AGTCCAGCTTCT

GGGACAGTTTGCCACCGTTTACAAGGCCAGAG





CDKN1A
NM_000389
 445
TGGAGACTCT
 446
GGCGTTTGGA
 447
CGGCGGCAGACC
 448
TGGAGACTCTCAGGGTCGAAAACGGCGGCAGACCAGCATGAC





CAGGGTCGAA

GTGGTAGAAA

AGCATGAC

AGATTTCTACCACTCCAAACGCC





A

TC









CDKN1C
NM_000076
 449
CGGCGATCAA
 450
CAGGCGCTGA
 451
CGGGCCTCTGAT
 452
CGGCGATCAAGAAGCTGTCCGGGCCTCTGATCTCCGATTTCTT





GAAGCTGT

TCTCTTGC

CTCCGATTTCTT

CGCCAAGCGCAAGAGATCAGCGCCTG





CDKN2B
NM_004936
 453
GACGCTGCAG
 454
GCGGGAATCT
 455
CACAGGATGCTG
 456
GACGCTGCAGAGCACCTTTGCACAGGATGCTGGCCTTTGCTCT





AGCACCTT

CTCCTCAGT

GCCTTTGCTCTT

TACTACACTGAGGAGAGATTCCCGC





CDKN2C
NM_001262
 457
GAGCACTGGG
 458
CAAAGGCGAA
 459
CCTGTAACTTGA
 460
GAGCACTGGGCAATCGTTACGACCTGTAACTTGAGGGCCACC





CAATCGTTAC

CGGGAGTAG

GGGCCACCGAAC

GAACTGCTACTCCCGTTCGCCTTTG





CDKN3
NM_005192
 461
TGGATCTCTA
 462
ATGTCAGGAG
 463
ATCACCCATCAT
 464
TGGATCTCTACCAGCAATGTGGAATTATCACCCATCATCATCC





CCAGCAATGT

TCCCTCCATC

CATCCAATCGCA

AATCGCAGATGGAGGGACTCCTGACAT





G











CDS2
NM_003818
 465
GGGCTTCTTT
 466
ACAGGGCAGA
 467
CCCGGACATCAC
 468
GGGCTTCTTTGCTACTGTGGTGTTTGGCCTTCTGCTGTCCTAT





GCTACTGTGG

CAAAGCATCT

ATAGGACAGCAG

GTGATGTCCGGGTACAGATGCTTTGTCTGCCCTGT





CENPF
NM_016343
 469
CTCCCGTCAA
 470
GGGTGAGTCT
 471
ACACTGGACCAG
 472
CTCCCGTCAACAGCGTTCTTTCCAAACACTGGACCAGGAGTGC





CAGCGTTC

GGCCTTCA

GAGTGCATCCAG

ATCCAGATGAAGGCCAGACTCACCC





CHAF1A
NM_005483
 473
GAACTCAGTG
 474
GCTCTGTAGC
 475
TGCACGTACCAG
 476
GAACTCAGTGTATGAGAAGCGGCCTGACTTCAGGATGTGCTG





TATGAGAAGC

ACCTGCGG

CACATCCTGAAG

GTACGTGCACCCGCAGGTGCTACAGAGC





GG











CHN1
NM_001822
 477
TTACGACGCT
 478
TCTCCCTGAT
 479
CCACCATTGGCC
 480
TTACGACGCTCGTGAAAGCACATACCACTAAGCGGCCAATGGT





CGTGAAAGC

GCACATGTCT

GCTTAGTGGTAT

GGTAGACATGTGCATCAGGGAGA





CHRAC1
NM_017444
 481
TCTCGCTGCC
 482
CCTGGTTGAT
 483
ATCCGGGTCATC
 484
TCTCGCTGCCTCTATCCCGCATCCGGGTCATCATGAAGAGCTC





TCTATCCC

GCTGGACA

ATGAAGAGCTCC

CCCCGAGGTGTCCAGCATCAACCAGG





CKS2
NM_001827
 485
GGCTGGACGT
 486
CGCTGCAGAA
 487
CTGCGCCCGCTC
 488
GGCTGGACGTGGTTTTGTCTGCTGCGCCCGCTCTTCGCGCTCT





GGTTTTGTCT

AATGAAACGA

TTCGCG

CGTTTCATTTTCTGCAGCG





CLDN3
NM_001306
 489
ACCAACTGCG
 490
GGCGAGAAGG
 491
CAAGGCCAAGAT
 492
ACCAACTGCGTGCAGGACGACACGGCCAAGGCCAAGATCACC





TGCAGGAC

AACAGCAC

CACCATCGTGG

ATCGTGGCAGGCGTGCTGTTCCTTCTCGCC





CLTC
NM_004859
 493
ACCGTATGGA
 494
TGACTACAGG
 495
TCTCACATGCTG
 496
ACCGTATGGACAGCCACAGCCTGGCTTTGGGTACAGCATGTG





CAGCCACAG

ATCAGCGCTT

TACCCAAAGCCA

AGATGAAGCGCTGATCCTGTAGTCA







C









COL11A1
NM_001854
 497
GCCCAAGAGG
 498
GGACCTGGGT
 499
CTGCTCGACCTT
 500
GCCCAAGAGGGGAAGATGGCCCTGAAGGACCCAAAGGTCGA





GGAAGATG

CTCCAGTTG

TGGGTCCTTCAG

GCAGGCCCAACTGGAGACCCAGGTCC





COL1A1
NM_000088
 501
GTGGCCATCC
 502
CAGTGGTAGG
 503
TCCTGCGCCTGA
 504
GTGGCCATCCAGCTGACCTTCCTGCGCCTGATGTCCACCGAG





AGCTGACC

TGATGTTCTG

TGTCCACCG

GCCTCCCAGAACATCACCTACCACTG







GGA









COL1A2
NM_000089
 505
CAGCCAAGAA
 506
AAACTGGCTG
 507
TCTCCTAGCCAG
 508
CAGCCAAGAACTGGTATAGGAGCTCCAAGGACAAGAAACACG





CTGGTATAGG

CCAGCATTG

ACGTGTTTCTTG

TCTGGCTAGGAGAAACTATCAATGCTGGCAGCCAGTTT





AGCT



TCCTTG







COL3A1
NM_000090
 509
GGAGGTTCTG
 510
ACCAGGACTG
 511
CTCCTGGTCCCC
 512
GGAGGTTCTGGACCTGCTGGTCCTCCTGGTCCCCAAGGTGTC





GACCTGCTG

CCACGTTC

AAGGTGTCAAAG

AAAGGTGAACGTGGCAGTCCTGGT





COL4A1
NM_001845
 513
ACAAAGGCCT
 514
GAGTCCCAGG
 515
CTCCTTTGACAC
 516
ACAAAGGCCTCCCAGGATTGGATGGCATCCCTGGTGTCAAAG





CCCAGGAT

AAGACCTGCT

CAGGGATGCCAT

GAGAAGCAGGTCTTCCTGGGACTC





COL5A1
NM_000093
 517
CTCCCTGGGA
 518
CTGGACCAGG
 519
CCAGGGAAACCA
 520
CTCCCTGGGAAAGATGGCCCTCCAGGATTACGTGGTTTCCCTG





AAGATGGC

AAGCCCTC

CGTAATCCTGGA

GGGACCGAGGGCTTCCTGGTCCAG





COL5A2
NM_000393
 521
GGTCGAGGAA
 522
GCCTGGAGGT
 523
CCAGGAAATCCT
 524
GGTCGAGGAACCCAAGGTCCGCCTGGTGCTACAGGATTTCCT





CCCAAGGT

CCAACTCTG

GTAGCACCAGGC

GGTTCTGCGGGCAGAGTTGGACCTCCAGGC





COL6A1
NM_001848
 525
GGAGACCCTG
 526
TCTCCAGGGA
 527
CTTCTCTTCCCT
 528
GGAGACCCTGGTGAAGCTGGCCCGCAGGGTGATCAGGGAAG





GTGAAGCTG

CACCAACG

GATCACCCTGCG

AGAAGGCCCCGTTGGTGTCCCTGGAGA





COL6A3
NM_004369
 529
GAGAGCAAGC
 530
AACAGGGAAC
 531
CCTCTTTGACGG
 532
GAGAGCAAGCGAGACATTCTGTTCCTCTTTGACGGCTCAGCCA





GAGACATTCT

TGGCCCAC

CTCAGCCAATCT

ATCTTGTGGGCCAGTTCCCTGTT





G











COL8A1
NM_001850
 533
TGGTGTTCCA
 534
CCCTGTAAAC
 535
CCTAAGGGAGAG
 536
TGGTGTTCCAGGGCTTCTCGGACCTAAGGGAGAGCCAGGAAT





GGGCTTCT

CCTGATCCC

CCAGGAATCCCA

CCCAGGGGATCAGGGTTTACAGGG





COL9A2
NM_001852
 537
GGGAACCATC
 538
ATTCCGGGTG
 539
ACACAGGAAATC
 540
GGGAACCATCCAGGGTCTGGAAGGCAGTGCGGATTTCCTGTG





CAGGGTCT

GACAGTTG

CGCACTGCCTTC

TCCAACCAACTGTCCACCCGGAAT





CRISP3
NM_006061
 541
TCCCTTATGA
 542
AACCATTGGT
 543
TGCCAGTTGCCC
 544
TCCCTTATGAACAAGGAGCACCTTGTGCCAGTTGCCCAGATAA





ACAAGGAGCA

GCATAGTCCA

AGATAACTGTGA

CTGTGACGATGGACTATGCACCAATGGTT





C

T









CSF1
NM_000757
 545
TGCAGCGGCT
 546
CAACTGTTCC
 547
TCAGATGGAGAC
 548
TGCAGCGGCTGATTGACAGTCAGATGGAGACCTCGTGCCAAA





GATTGACA

TGGTCTACAA

CTCGTGCCAAAT

TTACATTTGAGTTTGTAGACCAGGAACAGTTG







ACTCA

TACA







CSK
NM_004383
 549
CCTGAACATG
 550
CATCACGTCT
 551
TCCCGATGGTCT
 552
CCTGAACATGAAGGAGCTGAAGCTGCTGCAGACCATCGGGAA





AAGGAGCTGA

CCGAACTCC

GCAGCAGCT

GGGGGAGTTCGGAGACGTGATG





CSRP1
NM_004078
 553
ACCCAAGACC
 554
GCAGGGGTGG
 555
CCACCCTTCTCC
 556
ACCCAAGACCCTGCCTCTTCCACTCCACCCTTCTCCAGGGACC





CTGCCTCT

AGTGATGT

AGGGACCCTTAG

CTTAGATCACATCACTCCACCCCTGC





CTGF
NM_001901
 557
GAGTTCAAGT
 558
AGTTGTAATG
 559
AACATCATGTTC
 560
GAGTTCAAGTGCCCTGACGGCGAGGTCATGAAGAAGAACATG





GCCCTGACG

GCAGGCACAG

TTCTTCATGACC

ATGTTCATCAAGACCTGTGCCTGCCATTACAACT









TCGC







CTHRC1
NM_138455
 561
TGGCTCACTT
 562
TCAGCTCCAT
 563
CAACGCTGACAG
 564
TGGCTCACTTCGGCTAAAATGCAGAAATGCATGCTGTCAGCGT





CGGCTAAAAT

TGAATGTGAA

CATGCATTTCTG

TGGTATTTCACATTCAATGGAGCTGA







A









CTNNA1
NM_001903
 565
CGTTCCGATC
 566
AGGTCCCTGT
 567
ATGCCTACAGCA
 568
CGTTCCGATCCTCTATACTGCATCCCAGGCATGCCTACAGCAC





CTCTATACTG

TGGCCTTATA

CCCTGATGTCGC

CCTGATGTCGCAGCCTATAAGGCCAACAGGGACCT





CAT

GG

A







CTNNB1
NM_001904
 569
GGCTCTTGTG
 570
TCAGATGACG
 571
AGGCTCAGTGAT
 572
GGCTCTTGTGCGTACTGTCCTTCGGGCTGGTGACAGGGAAGA





CGTACTGTCC

AAGAGCACAG

GTCTTCCCTGTC

CATCACTGAGCCTGCCATCTGTGCTCTTCGTCATCTGA





TT

ATG

ACCAG







CTNND1
NM_001331
 573
CGGAAACTTC
 574
CTGAATCCTT
 575
TTGATGCCCTCA
 576
CGGAAACTTCGGGAATGTGATGGTTTAGTTGATGCCCTCATTT





GGGAATGTGA

CTGCCCAATC

TTTTCATTGTTC

TCATTGTTCAGGCTGAGATTGGGCAGAAGGATTCAG







TC

AGGC







CTNND2
NM_001332
 577
GCCCGTCCCT
 578
CTCACACCCA
 579
CTATGAAACGAG
 580
GCCCGTCCCTACAGTGAACTGAACTATGAAACGAGCCACTACC





ACAGTGAAC

GGAGTCGG

CCACTACCCGGC

CGGCCTCCCCCGACTCCTGGGTGTGAG





CTSB
NM_001908
 581
GGCCGAGATC
 582
GCAGGAAGTC
 583
CCCCGTGGAGGG
 584
GGCCGAGATCTACAAAAACGGCCCCGTGGAGGGAGCTTTCTC





TACAAAAACG

CGAATACACA

AGCTTTCTC

TGTGTATTCGGACTTCCTGC





CTSD
NM_001909
 585
GTACATGATC
 586
GGGACAGCTT
 587
ACCCTGCCCGCG
 588
GTACATGATCCCCTGTGAGAAGGTGTCCACCCTGCCCGCGAT





CCCTGTGAGA

GTAGCCTTTG

ATCACACTGA

CACACTGAAGCTGGGAGGCAAAGGCTACAAGCTGTCCC





AGGT

C









CTSK
NM_000396
 589
AGGCTTCTCT
 590
CCACCTCTTC
 591
CCCCAGGTGGTT
 592
AGGCTTCTCTTGGTGTCCATACATATGAACTGGCTATGAACCA





TGGTGTCCAT

ACTGGTCATG

CATAGCCAGTTC

CCTGGGGGACATGACCAGTGAAGAGGTGG





AC

T









CTSL2
NM_001333
 593
TGTCTCACTG
 594
ACCATTGCAG
 595
CTTGAGGACGCG
 596
TGTCTCACTGAGCGAGCAGAATCTGGTGGACTGTTCGCGTCCT





AGCGAGCAGA

CCCTGATTG

AACAGTCCACCA

CAAGGCAATCAGGGCTGCAATGGT





A











CTSS
NM_004079
 597
TGACAACGGC
 598
TCCATGGCTT
 599
TGATAACAAGGG
 600
TGACAACGGCTTTCCAGTACATCATTGATAACAAGGGCATCGA





TTTCCAGTAC

TGTAGGGATA

CATCGACTCAGA

CTCAGACGCTTCCTATCCCTACAAAGCCATGGA





AT

GG

CGCT







CUL1
NM_003592
 601
ATGCCCTGGT
 602
GCGACCACAA
 603
CAGCCACAAAGC
 604
ATGCCCTGGTAATGTCTGCATTCAACAATGACGCTGGCTTTGT





AATGTCTGCA

GCCTTATCAA

CAGCGTCATTGT

GGCTGCTCTTGATAAGGCTTGTGGTCGC





T

G









CXCL12
NM_000609
 605
GAGCTACAGA
 606
TTTGAGATGC
 607
TTCTTCGAAAGC
 608
GAGCTACAGATGCCCATGCCGATTCTTCGAAAGCCATGTTGCC





TGCCCATGC

TTGACGTTGG

CATGTTGCCAGA

AGAGCCAACGTCAAGCATCTCAAA





CXCR4
NM_003467
 609
TGACCGCTTC
 610
AGGATAAGGC
 611
CTGAAACTGGAA
 612
TGACCGCTTCTACCCCAATGACTTGTGGGTGGTTGTGTTCCAG





TACCCCAATG

CAACCATGAT

CACAACCACCCA

TTTCAGCACATCATGGTTGGCCTTATCCT







GT

CAAG







CXCR7
NM_020311
 613
CGCCTCAGAA
 614
GTTGCATGGC
 615
CTCAGAGCCAGG
 616
CGCCTCAGAACGATGGATCTGCATCTCTTCGACTACTCAGAGC





CGATGGAT

CAGCTGAT

GAACTTCTCGGA

CAGGGAACTTCTCGGACATCAGCTGGCCATGCAAC





CYP3A5
NM_000777
 617
TCATTGCCCA
 618
GACAGGCTTG
 619
TCCCGCCTCAAG
 620
TCATTGCCCAGTATGGAGATGTATTGGTGAGAAACTTGAGGCG





GTATGGAGAT

CCTTTCTCTG

TTTCTCACCAAT

GGAAGCAGAGAAAGGCAAGCCTGTC





G











CYR61
NM_001554
 621
TGCTCATTCT
 622
GTGGCTGCAT
 623
CAGCACCCTTGG
 624
TGCTCATTCTTGAGGAGCATTAAGGTATTTCGAAACTGCCAAG





TGAGGAGCAT

TAGTGTCCAT

CAGTTTCGAAAT

GGTGCTGGTGCGGATGGACACTAATGCAGCCAC





DAG1
NM_004393
 625
GTGACTGGGC
 626
ATCCCACTTG
 627
CAAGTCAGAGTT
 628
GTGACTGGGCTCATGCCTCCAAGTCAGAGTTTCCCTGGTGCC





TCATGCCT

TGCTCCTGTC

TCCCTGGTGCCC

CCAGAGACAGGAGCACAAGTGGGAT





DAP
NM_004394
 629
CCAGCCTTTC
 630
GACCAGGTCT
 631
CTCACCAGCTGG
 632
CCAGCCTTTCTGGTGCTGTTCTCCAGTTCACGTCTGCCAGCTG





TGGTGCTG

GCCTCTGC

CAGACGTGAACT

GTGAGGGCAGAGGCAGACCTGGTC





DAPK1
NM_004938
 633
CGCTGACATC
 634
TCTCTTTCAG
 635
TCATATCCAAAC
 636
CGCTGACATCATGAATGTTCCTCGACCGGCTGGAGGCGAGTTT





ATGAATGTTC

CAACGATGTG

TCGCCTCCAGCC

GGATATGACAAAGACACATCGTTGCTGAAAGAGA





CT

TCTT

G







DARC
NM_002036
 637
GCCCTCATTA
 638
CAGACAGAAG
 639
TCAGCGCCTGTG
 640
GCCCTCATTAGTCCTTGGCTCTTATCTTGGAAGCACAGGCGCT





GTCCTTGGCT

GGCTGGGAC

CTTCCAAGATAA

GACAGCCGTCCCAGCCCTTCTGTCTG





DDIT4
NM_019058
 641
CCTGGCGTCT
 642
CGAAGAGGAG
 643
CTAGCCTTTGGG
 644
CCTGGCGTCTGTCCTCACCATGCCTAGCCTTTGGGACCGCTTC





GTCCTCAC

GTGGACGA

ACCGCTTCTCGT

TCGTCGTCGTCCACCTCCTCTTCG





DDR2
NM_
 645
CTATTACCGG
 646
CCCAGCAAGA
 647
AGTGCTCCCTAT
 648
CTATTACCGGATCCAGGGCCGGGCAGTGCTCCCTATCCGCTG



001014796

ATCCAGGGC

TACTCTCCCA

CCGCTGGATGTC

GATGTCTTGGGAGAGTATCTTGCTGGG





DES
NM_001927
 649
ACTTCTCACT
 650
GCTCCACCTT
 651
TGAACCAGGAGT
 652
ACTTCTCACTGGCCGACGCGGTGAACCAGGAGTTTCTGACCA





GGCCGACG

CTCGTTGGT

TTCTGACCACGC

CGCGCACCAACGAGAAGGTGGAGC





DHRS9
NM_005771
 653
GGAGAAAGGT
 654
CAGTCAGTGG
 655
ATCAATAATGCT
 656
GGAGAAAGGTCTCTGGGGTCTGATCAATAATGCTGGTGTTCCC





CTCTGGGGTC

GAGCCAGC

GGTGTTCCCGGC

GGCGTGCTGGCTCCCACTGACTG





DHX9
NM_001357
 657
GTTCGAACCA
 658
TCCAGTTGGA
 659
CCAAGGAACCAC
 660
GTTCGAACCATCTCAGCGACAAAACCAAGTGGGTGTGGTTCCT





TCTCAGCGAC

TTGTGGAGGT

ACCCACTTGGTT

TGGTCACCTCCACAATCCAACTGGA





DIAPH1
NM_005219
 661
CAAGCAGTCA
 662
AGTTTTGCTC
 663
TTCTTCTGTCTC
 664
CAAGCAGTCAAGGAGAACCAGAAGCGGCGGGAGACAGAAGA





AGGAGAACCA

GCCTCATCTT

CCGCCGCTTC

AAAGATGAGGCGAGCAAAACT





DICER1
NM_177438
 665
TCCAATTCCA
 666
GGCAGTGAAG
 667
AGAAAAGCTGTT
 668
TCCAATTCCAGCATCACTGTGGAGAAAAGCTGTTTGTCTCCCC





GCATCACTGT

GCGATAAAGT

TGTCTCCCCAGC

AGCATACTTTATCGCCTTCACTGCC









A







DIO2
NM_013989
 669
CTCCTTTCAC
 670
AGGAAGTCAG
 671
ACTCTTCCACCA
 672
CTCCTTTCACGAGCCAGCTGCCAGCCTTCCGCAAACTGGTGG





GAGCCAGC

CCACTGAGGA

GTTTGCGGAAGG

AAGAGTTCTCCTCAGTGGCTGACTTCCT





DLC1
NM_006094
 673
GATTCAGACG
 674
CACCTCTTGC
 675
AAAGTCCATTTG
 676
GATTCAGACGAGGATGAGCCTTGTGCCATCAGTGGCAAATGG





AGGATGAGCC

TGTCCCTTTG

CCACTGATGGCA

ACTTTCCAAAGGGACAGCAAGAGGTG





DLGAP1
NM_004746
 677
CTGCTGAGCC
 678
AGCCTGGAAG
 679
CGCAGACCACCC
 680
CTGCTGAGCCCAGTGGAGCACCACCCCGCAGACCACCCATAC





CAGTGGAG

GAGTTCCG

ATACTACACCCA

TACACCCAGCGGAACTCCTTCCAGGCT





DLL4
NM_019074
 681
CACGGAGGTA
 682
AGAAGGAAGG
 683
CTACCTGGACAT
 684
CACGGAGGTATAAGGCAGGAGCCTACCTGGACATCCCTGCTC





TAAGGCAGGA

TCCAGCCG

CCCTGCTCAGCC

AGCCCCGCGGCTGGACCTTCCTTCT





G











DNM3
NM_015569
 685
CTTTCCCACC
 686
AAGGACCTTC
 687
CATATCGCTGAC
 688
CTTTCCCACCCGGCTTACAGACATATCGCTGACCGAATGGGAA





CGGCTTAC

TGCAGGTGTG

CGAATGGGAACC

CCCCACACCTGCAGAAGGTCCTT





DPP4
NM_001935
 689
GTCCTGGGAT
 690
GTACTCCCAC
 691
CGGCTATTCCAC
 692
GTCCTGGGATCGGGAAGTGGCGTGTTCAAGTGTGGAATAGCC





CGGGAAGT

CGGGATACAG

ACTTGAACACGC

GTGGCGCCTGTATCCCGGTGGGAGTAC





DPT
NM_001937
 693
CACCTAGAAG
 694
CAGTAGCTCC
 695
TTCCTAGGAAGG
 696
CACCTAGAAGCCTGCCCACGATTCCTAGGAAGGCTGGCAGAC





CCTGCCCAC

CCAGGGTTC

CTGGCAGACACC

ACCCTGGAACCCTGGGGAGCTACTG





DUSP1
NM_004417
 697
AGACATCAGC
 698
GACAAACACC
 699
CGAGGCCATTGA
 700
AGACATCAGCTCCTGGTTCAACGAGGCCATTGACTTCATAGAC





TCCTGGTTCA

CTTCCTCCAG

CTTCATAGACTC

TCCATCAAGAATGCTGGAGGAAGGGTGTTTGTC









CA







DUSP6
NM_001946
 701
CATGCAGGGA
 702
TGCTCCTACC
 703
TCTACCCTATGC
 704
CATGCAGGGACTGGGATTCGAGGACTTCCAGGCGCATAGGGT





CTGGGATT

CTATCATTTG

GCCTGGAAGTCC

AGAACCAAATGATAGGGTAGGAGCA







G









DVL1
NM_004421
 705
TCTGTCCCAC
 706
TCAGACTGTT
 707
CTTGGAGCAGCC
 708
TCTGTCCCACCTGCTGCTGCCCCTTGGAGCAGCCTGCACCTTC





CTGCTGCT

GCCGGATG

TGCACCTTCTCT

TCTCCTCCCATCCGGCAACAGTCTGA





DYNLL1
NM_
 709
GCCGCCTACC
 710
GCCTGACTCC
 711
ACCCACGTCAGT
 712
GCCGCCTACCTCACAGACTTGTGAGCACTCACTGACGTGGGT



001037494

TCACAGAC

AGCTCTCCT

GAGTGCTCACAA

AGCGCCCAGGGCCTGCGGGGCGCAGGAGAGCTGGAGTCAGG











C





EBNA1BP2
NM_006824
 713
TGCGGCGAGA
 714
GTGACAAGGG
 715
CCCGCTCTCGGA
 716
TGCGGCGAGATGGACACTCCCCCGCTCTCGGATTCGGAGTCG





TGGACACT

ATTCATCGGA

TTCGGAGTCG

GAATCCGATGAATCCCTTGTCAC







TT









ECE1
NM_001397
 717
ACCTTGGGAT
 718
GGACCAGGAC
 719
TCCACTCTCGAT
 720
ACCTTGGGATCTGCCTCCAAGCTGGTGCAGGGTATCGAGAGT





CTGCCTCC

CTCCATCTG

ACCCTGCACCAG

GGATTCCAGATGGAGGTCCTGGTCC





EDN1
NM_001955
 721
TGCCACCTGG
 722
TGGACCTAGG
 723
CACTCCCGAGCA
 724
TGCCACCTGGACATCATTTGGGTCAACACTCCCGAGCACGTTG





ACATCATTTG

GCTTCCAAGT

CGTTGTTCCGT

TTCCGTATGGACTTGGAAGCCCTAGGTCCA







C









EDNRA
NM_001957
 725
TTTCCTCAAA
 726
TTACACATCC
 727
CCTTTGCCTCAG
 728
TTTCCTCAAATTTGCCTCAAGATGGAAACCCTTTGCCTCAGGG





TTTGCCTCAA

AACCAGTGCC

GGCATCCTTTT

CATCCTTTTGGCTGGCACTGGTTGGATGTGTAA





G











EFNB2
NM_004093
 729
TGACATTATC
 730
GTAGTCCCCG
 731
CGGACAGCGTCT
 732
TGACATTATCATCCCGCTAAGGACTGCGGACAGCGTCTTCTGC





ATCCCGCTAA

CTGACCTTCT

TCTGCCCTCACT

CCTCACTACGAGAAGGTCAGCGGGGACTAC





GGA

C









EGF
NM_001963
 733
CTTTGCCTTG
 734
AAATACCTGA
 735
AGAGTTTAACAG
 736
CTTTGCCTTGCTCTGTCACAGTGAAGTCAGCCAGAGCAGGGCT





CTCTGTCACA

CACCCTTATG

CCCTGCTCTGGC

GTTAAACTCTGTGAAATTTGTCATAAGGGTGTCAGGTATTT





GT

ACAAATT

TGACTT







EGR1
NM_001964
 737
GTCCCCGCTG
 738
CTCCAGCTTA
 739
CGGATCCTTTCC
 740
GTCCCCGCTGCAGATCTCTGACCCGTTCGGATCCTTTCCTCAC





CAGATCTCT

GGGTAGTTGT

TCACTCGCCCA

TCGCCCACCATGGACAACTACCCTAAGCTGGAG







CCAT









EGR3
NM_004430
 741
CCATGTGGAT
 742
TGCCTGAGAA
 743
ACCCAGTCTCAC
 744
CCATGTGGATGAATGAGGTGTCTCCTTTCCATACCCAGTCTCA





GAATGAGGTG

GAGGTGAGGT

CTTCTCCCCACC

CCTTCTCCCCACCCTACCTCACCTCTTCTCAGGCA





EIF2C2
NM_012154
 745
GCACTGTGGG
 746
ATGTTTGGTG
 747
CGGGTCACATTG
 748
GCACTGTGGGCAGATGAAGAGGAAGTACCGCGTCTGCAATGT





CAGATGAA

ACTGGCGG

CAGACACGGTAC

GACCCGGCGGCCCGCCAGTCACCAAACAT





EIF2S3
NM_001415
 749
CTGCCTCCCT
 750
GGTGGCAAGT
 751
TCTCGTGCTTCA
 752
CTGCCTCCCTGATTCAAGTGATTCTCGTGCTTCAGCCTCCCAT





GATTCAAGTG

GCCTGTAATA

GCCTCCCATGTA

GTAGCTGATATTACAGGCACTTGCCACC







TC









EIF3H
NM_003756
 753
CTCATTGCAG
 754
GCCATGAAGA
 755
CAGAACATCAAG
 756
CTCATTGCAGGCCAGATAAACACTTACTGCCAGAACATCAAGG





GCCAGATAAA

GCTTGCCTA

GAGTTCACTGCC

AGTTCACTGCCCAAAACTTAGGCAAGCTCTTCATGGC









CA







EIF4E
NM_001968
 757
GATCTAAGAT
 758
TTAGATTCCG
 759
ACCACCCCTACT
 760
GATCTAAGATGGCGACTGTCGAACCGGAAACCACCCCTACTC





GGCGACTGTC

TTTTCTCCTC

CCTAATCCCCCG

CTAATCCCCCGACTACAGAAGAGGAGAAAACGGAATCTAA





GAA

TTCTG

ACT







EIF5
NM_001969
 761
GAATTGGTCT
 762
TCCAGGTATA
 763
CCACTTGCACCC
 764
GAATTGGTCTCCAGCTGCCTTTGATCAAGATTCGGGTGCAAGT





CCAGCTGCC

TGGCTCCTGC

GAATCTTGATCA

GGAGCAGGAGCCATATACCTGGA





ELK4
NM_001973
 765
GATGTGGAGA
 766
AGTCATTGCG
 767
ATAAACCACCTC
 768
GATGTGGAGAATGGAGGGAAAGATAAACCACCTCAGCCTGGT





ATGGAGGGAA

GCTAGAGGTC

AGCCTGGTGCCA

GCCAAGACCTCTAGCCGCAATGACT





ENPP2
NM_006209
 769
CTCCTGCGCA
 770
TCCCTGGATA
 771
TAACTTCCTCTG
 772
CTCCTGCGCACTAATACCTTCAGGCCAACCATGCCAGAGGAA





CTAATACCTT

ATTGGGTCTG

GCATGGTTGGCC

GTTACCAGACCCAATTATCCAGGGA





C











ENY2
NM_020189
 773
CCTCAAAGAG
 774
CCTCTTTACA
 775
CTGATCCTTCCA
 776
CCTCAAAGAGTTGCTGAGAGCTAAATTAATTGAATGTGGCTGG





TTGCTGAGAG

GTGTGCCTTC

GCCACATTCAAT

AAGGATCAGTTGAAGGCACACTGTAAAGAGG





C

A

TAATTT







EPHA2
NM_004431
 777
CGCCTGTTCA
 778
GTGGCGTGCC
 779
TGCGCCCGATGA
 780
CGCCTGTTCACCAAGATTGACACCATTGCGCCCGATGAGATCA





CCAAGATTGA

TCGAAGTC

GATCACCG

CCGTCAGCAGCGACTTCGAGGCACGCCAC





C











EPHA3
NM_005233
 781
CAGTAGCCTC
 782
TTCGTCCCAT
 783
TATTCCAAATCC
 784
CAGTAGCCTCAAGCCTGACACTATATACGTATTCCAAATCCGA





AAGCCTGACA

ATCCAGCG

GAGCCCGAACAG

GCCCGAACAGCCGCTGGATATGGGACGAA





EPHB2
NM_004442
 785
CAACCAGGCA
 786
GTAATGCTGT
 787
CACCTGATGCAT
 788
CAACCAGGCAGCTCCATCGGCAGTGTCCATCATGCATCAGGT





GCTCCATC

CCACGGTGC

GATGGACACTGC

GAGCCGCACCGTGGACAGCATTAC





EPHB4
NM_004444
 789
TGAACGGGGT
 790
AGGTACCTCT
 791
CGTCCCATTTGA
 792
TGAACGGGGTATCCTCCTTAGCCACGGGGCCCGTCCCATTTG





ATCCTCCTTA

CGGTCAGTGG

GCCTGTCAATGT

AGCCTGTCAATGTCACCACTGACCGAGAGGTACCT





ERBB2
NM_004448
 793
CGGTGTGAGA
 794
CCTCTCGCAA
 795
CCAGACCATAGC
 796
CGGTGTGAGAAGTGCAGCAAGCCCTGTGCCCGAGTGTGCTAT





AGTGCAGCAA

GTGCTCCAT

ACACTCGGGCAC

GGTCTGGGCATGGAGCACTTGCGAGAGG





ERBB3
NM_001982
 797
CGGTTATGTC
 798
GAACTGAGAC
 799
CCTCAAAGGTAC
 800
CGGTTATGTCATGCCAGATACACACCTCAAAGGTACTCCCTCC





ATGCCAGATA

CCACTGAAGA

TCCCTCCTCCCG

TCCCGGGAAGGCACCCTTTCTTCAGTGGGTCTCAGTTC





CAC

AAGG

G







ERBB4
NM_005235
 801
TGGCTCTTAA
 802
CAAGGCATAT
 803
TGTCCCACGAAT
 804
TGGCTCTTAATCAGTTTCGTTACCTGCCTCTGGAGAATTTACG





TCAGTTTCGT

CGATCCTCAT

AATGCGTAAATT

CATTATTCGTGGGACAAAACTTTATGAGGATCGATATGCCTTG





TACCT

AAAGT

CTCCAG







ERCC1
NM_001983
 805
GTCCAGGTGG
 806
CGGCCAGGAT
 807
CAGCAGGCCCTC
 808
GTCCAGGTGGATGTGAAAGATCCCCAGCAGGCCCTCAAGGAG





ATGTGAAAGA

ACACATCTTA

AAGGAGCTG

CTGGCTAAGATGTGTATCCTGGCCG





EREG
NM_001432
 809
TGCTAGGGTA
 810
TGGAGACAAG
 811
TAAGCCATGGCT
 812
TGCTAGGGTAAACGAAGGCATAATAAGCCATGGCTGACCTCTG





AACGAAGGCA

TCCTGGCAC

GACCTCTGGAGC

GAGCACCAGGTGCCAGGACTTGTCTCCA





ERG
NM_004449
 813
CCAACACTAG
 814
CCTCCGCCAG
 815
AGCCATATGCCT
 816
CCAACACTAGGCTCCCCACCAGCCATATGCCTTCTCATCTGGG





GCTCCCCA

GTCTTTAGT

TCTCATCTGGGC

CACTTACTACTAAAGACCTGGCGGAGG





ESR1
NM_000125
 817
CGTGGTGCCC
 818
GGCTAGTGGG
 819
CTGGAGATGCTG
 820
CGTGGTGCCCCTCTATGACCTGCTGCTGGAGATGCTGGACGC





CTCTATGAC

CGCATGTAG

GACGCCC

CCACCGCCTACATGCGCCCACTAGCC





ESR2
NM_001437
 821
TGGTCCATCG
 822
TGTTCTAGCG
 823
ATCTGTATGCGG
 824
TGGTCCATCGCCAGTTATCACATCTGTATGCGGAACCTCAAAA





CCAGTTATCA

ATCTTGCTTC

AACCTCAAAAGA

GAGTCCCTGGTGTGAAGCAAGATCGCTAGAACA







ACA

GTCCCT







ETV1
NM_004956
 825
TCAAACAAGA
 826
AACTGCCAGA
 827
ATCGGGAAGGAC
 828
TCAAACAAGAGCCAGGAATGTATCGGGAAGGACCCACATACC





GCCAGGAATG

GCTGAAGTGA

CCACATACCAAC

AACGGCGAGGATCACTTCAGCTCTGGCAGTT





ETV4
NM_001986
 829
TCCAGTGCCT
 830
ACTGTCCAAG
 831
CAGACAAATCGC
 832
TCCAGTGCCTATGACCCCCCCAGACAAATCGCCATCAAGTCCC





ATGACCCC

GGCACCAG

CATCAAGTCCCC

CTGCCCCTGGTGCCCTTGGACAGT





EZH2
NM_004456
 833
TGGAAACAGC
 834
CACCGAACAC
 835
TCCTGACTTCTG
 836
TGGAAACAGCGAAGGATACAGCCTGTGCACATCCTGACTTCTG





GAAGGATACA

TCCCTAGTCC

TGAGCTCATTGC

TGAGCTCATTGCGCGGGACTAGGGAGTGTTCGGTG









G







F2R
NM_001992
 837
AAGGAGCAAA
 838
GCAGGGTTTC
 839
CCCGGGCTCAAC
 840
AAGGAGCAAACCATCCAGGTGCCCGGGCTCAACATCACTACC





CCATCCAGG

ATTGAGCAC

ATCACTACCTGT

TGTCATGATGTGCTCAATGAAACCCTGC





FAAH
NM_001441
 841
GACAGCGTAG
 842
AGCTGAACAT
 843
TGCCCTTCGTGC
 844
GACAGCGTAGTGGTGCATGTGCTGAAGCTGCAGGGTGCCGTG





TGGTGCATGT

GGACTGTGGA

ACACCAATG

CCCTTCGTGCACACCAATGTTCCACAGTCCATGTTCAGCT





FABP5
NM_001444
 845
GCTGATGGCA
 846
CTTTCCTTCC
 847
CCTGATGCTGAA
 848
GCTGATGGCAGAAAAACTCAGACTGTCTGCAACTTTACAGATG





GAAAAACTCA

CATCCCACT

CCAATGCACCAT

GTGCATTGGTTCAGCATCAGGAGTGGGATGGGAAGGAAAG





FADD
NM_003824
 849
GTTTTCGCGA
 850
CTCCGGTGCC
 851
AACGCGCTCTTG
 852
GTTTTCGCGAGATAACGGTCGAAAACGCGCTCTTGTCGATTTC





GATAACGGTC

TGATTCAC

TCGATTTCCTGT

CTGTAGTGAATCAGGCACCGGAG





FAM107A
NM_007177
 853
AAGTCAGGGA
 854
GCTGGCCCTA
 855
AATTGCCACACT
 856
AAGTCAGGGAAAACCTGCGGAGAATTGCCACACTGACCAGCG





AAACCTGCG

CAGCTCTCT

GACCAGCGAAGA

AAGAGAGAGAGCTGTAGGGCCAGC





FAM13C
NM_198215
 857
ATCTTCAAAG
 858
GCTGGATACC
 859
TCCTGACTTTCT
 860
ATCTTCAAAGCGGAGAGCGGGAGGAGCCACGGAGAAAGTCAG





CGGAGAGCG

ACATGCTCTG

CCGTGGCTCCTC

GAGACAGAGCATGTGGTATCCAGC





FAM171B
NM_177454
 861
CCAGGAAGGA
 862
GTGGTCTGCC
 863
TGAAGATTTTGA
 864
CCAGGAAGGAAAAGCACTGTTGAAGATTTTGAAGCTAATACAT





AAAGCACTGT

CCTTCTTTTA

AGCTAATACATC

CCCCCACTAAAAGAAGGGGCAGACCAC









CCCCAC







FAM49B
NM_016623
 865
AGATGCAGAA
 866
GCTGGATTGC
 867
TGGCCAGCTCCT
 868
AGATGCAGAAGGCATCTTGGAGGACTTGCAGTCATACAGAGG





GGCATCTTGG

CTCTCGTATT

CTGTATGACTGC

AGCTGGCCACGAAATACGAGAGGCAATCCAGC





FAM73A
NM_198549
 869
TGAGAAGGTG
 870
GGCCATTAAA
 871
AAGACCTCATGC
 872
TGAGAAGGTGCGCTATTCAAGTACAGAGACTTTAGCTGAAGAC





CGCTATTCAA

AGCTCAGTGC

AGTTACTCATTC

CTCATGCAGTTACTCATTCGCCGCACTGAGCTTTTAATGGCC









GCC







FAP
NM_004460
 873
GTTGGCTCAC
 874
GACAGGACCG
 875
AGCCACTGCAAA
 876
GTTGGCTCACGTGGGTTACTGATGAACGAGTATGTTTGCAGTG





GTGGGTTAC

AAACATTCTG

CATACTCGTTCA

GCTAAAAAGAGTCCAGAATGTTTCGGTCCTGTC









TCA







FAS
NM_000043
 877
GGATTGCTCA
 878
GGCATTAACA
 879
TCTGGACCCTCC
 880
GGATTGCTCAACAACCATGCTGGGCATCTGGACCCTCCTACCT





ACAACCATGC

CTTTTGGACG

TACCTCTGGTTC

CTGGTTCTTACGTCTGTTGCTAGATTATCGTCCAAAAGTGTTA





T

ATAA

TTACGT

ATGCC





FASLG
NM_000639
 881
GCACTTTGGG
 882
GCATGTAAGA
 883
ACAACATTCTCG
 884
GCACTTTGGGATTCTTTCCATTATGATTCTTTGTTACAGGCAC





ATTCTTTCCA

AGACCCTCAC

GTGCCTGTAACA

CGAGAATGTTGTATTCAGTGAGGGTCTTCTTACATGC





TTAT

TGAA

AAGAA







FASN
NM_004104
 885
GCCTCTTCCT
 886
GCTTTGCCCG
 887
TCGCCCACCTAC
 888
GCCTCTTCCTGTTCGACGGCTCGCCCACCTACGTACTGGCCTA





GTTCGACG

GTAGCTCT

GTACTGGCCTAC

CACCCAGAGCTACCGGGCAAAGC





FCGR3A
NM_000569
 889
GTCTCCAGTG
 890
AGGAATGCAG
 891
CCCATGATCTTC
 892
GTCTCCAGTGGAAGGGAAAAGCCCATGATCTTCAAGCAGGGA





GAAGGGAAAA

CTACTCACTG

AAGCAGGGAAGC

AGCCCCAGTGAGTAGCTGCATTCCT







G









FGF10
NM_004465
 893
TCTTCCGTCC
 894
AGAGTTGGTG
 895
ACACCATGTCCT
 896
TCTTCCGTCCCTGTCACCTGCCAAGCCCTTGGTCAGGACATGG





CTGTCACCT

GCCTCTGGT

GACCAAGGGCTT

TGTCACCAGAGGCCACCAACTCT





FGF17
NM_003867
 897
GGTGGCTGTC
 898
TCTAGCCAGG
 899
TTCTCGGATCTC
 900
GGTGGCTGTCCTCAAAATCTGCTTCTCGGATCTCCCTCAGTCT





CTCAAAATCT

AGGAGTTTGG

CCTCAGTCTGCC

GCCCCCAGCCCCCAAACTCCTCCTGGCTAGA





FGF5
NM_004464
 901
GCATCGGTTT
 902
AACATATTGG
 903
CCATTGACTTTG
 904
GCATCGGTTTCCATCTGCAGATCTACCCGGATGGCAAAGTCAA





CCATCTGC

CTTCGTGGGA

CCATCCGGGTAG

TGGATCCCACGAAGCCAATATGTT





FGF6
NM_020996
 905
GGGCCATTAA
 906
CCCGGGACAT
 907
CATCCACCTTGC
 908
GGGCCATTAATTCTGACCACGTGCCTGAGAGGCAAGGTGGAT





TTCTGACCAC

AGTGATGAA

CTCTCAGGCAC

GGCCCTGGGACAGAAACTGTTCATCACTATGTCCCGGG





FGF7
NM_002009
 909
CCAGAGCAAA
 910
TCCCCTCCTT
 911
CAGCCCTGAGCG
 912
CCAGAGCAAATGGCTACAAATGTGAACTGTTCCAGCCCTGAGC





TGGCTACAAA

CCATGTAATC

ACACACAAGAAG

GACACACAAGAAGTTATGATTACATGGAAGGAGGGGA





FGFR2
NM_000141
 913
GAGGGACTGT
 914
GAGTGAGAAT
 915
TCCCAGAGACCA
 916
GAGGGACTGTTGGCATGCAGTGCCCTCCCAGAGACCAACGTT





TGGCATGCA

TCGATCCAAG

ACGTTCAAGCAG

CAAGCAGTTGGTAGAAGACTTGGATCGAATTCTCACTC







TCTTC

TTG







FGFR4
NM_002011
 917
CTGGCTTAAG
 918
ACGAGACTCC
 919
CCTTTCATGGGG
 920
CTGGCTTAAGGATGGACAGGCCTTTCATGGGGAGAACCGCAT





GATGGACAGG

AGTGCTGATG

AGAACCGCATT

TGGAGGCATTCGGCTGCGCCATCAGCACTGGAGTCTCGT





FKBP5
NM_004117
 921
CCCACAGTAG
 922
GGTTCTGGCT
 923
TCTCCCCAGTTC
 924
CCCACAGTAGAGGGGTCTCATGTCTCCCCAGTTCCACAGCAG





AGGGGTCTCA

TTCACGTCTG

CACAGCAGTGTC

TGTCACAGACGTGAAAGCCAGAACC





FLNA
NM_001456
 925
GAACCTGCGG
 926
GAAGACACCC
 927
TACCAGGCCCAT
 928
GAACCTGCGGTGGACACTTCCGGTGTCCAGTGCTATGGGCCT





TGGACACT

TGGCCCTC

AGCACTGGACAC

GGTATTGAGGGCCAGGGTGTCTTC





FLNC
NM_001458
 929
CAGGACAATG
 930
TGATGGTGTA
 931
ATGTGCTGTCAG
 932
CAGGACAATGGTGATGGCTCATGTGCTGTCAGCTACCTGCCCA





GTGATGGCT

CTCGCCAGG

CTACCTGCCCAC

CGGAGCCTGGCGAGTACACCATCA





FLT1
NM_002019
 933
GGCTCCTGAA
 934
TCCCACAGCA
 935
CTACAGCACCAA
 936
GGCTCCTGAATCTATCTTTGACAAAATCTACAGCACCAAGAGC





TCTATCTTTG

ATACTCCGTA

GAGCGACGTGTG

GACGTGTGGTCTTACGGAGTATTGCTGTGGGA





FLT4
NM_002020
 937
ACCAAGAAGC
 938
CCTGGAAGCT
 939
AGCCCGCTGACC
 940
ACCAAGAAGCTGAGGACCTGTGGCTGAGCCCGCTGACCATGG





TGAGGACCTG

GTAGCAGACA

ATGGAAGATCT

AAGATCTTGTCTGCTACAGCTTCCAGG





FN1
NM_002026
 941
GGAAGTGACA
 942
ACACGGTAGC
 943
ACTCTCAGGCGG
 944
GGAAGTGACAGACGTGAAGGTCACCATCATGTGGACACCGCC





GACGTGAAGG

CGGTCACT

TGTCCACATGAT

TGAGAGTGCAGTGACCGGCTACCGTGT





T











FOS
NM_005252
 945
CGAGCCCTTT
 946
GGAGCGGGCT
 947
TCCCAGCATCAT
 948
CGAGCCCTTTGATGACTTCCTGTTCCCAGCATCATCCAGGCCC





GATGACTTCC

GTCTCAGA

CCAGGCCCAG

AGTGGCTCTGAGACAGCCCGCTCC





T











FOXO1
NM_002015
 949
GTAAGCACCA
 950
GGGGCAGAGG
 951
TATGAACCGCCT
 952
GTAAGCACCATGCCCCACACCTCGGGTATGAACCGCCTGACC





TGCCCCAC

CACTTGTA

GACCCAAGTGAA

CAAGTGAAGACACCTGTACAAGTGCCTCTGCCCC





FOXP3
NM_014009
 953
CTGTTTGCTG
 954
GTGGAGGAAC
 955
TGTTTCCATGGC
 956
CTGTTTGCTGTCCGGAGGCACCTGTGGGGTAGCCATGGAAAC





TCCGGAGG

TCTGGGAATG

TACCCCACAGGT

AGCACATTCCCAGAGTTCCTCCAC





FOXQ1
NM_033260
 957
TGTTTTTGTC
 958
TGGAAAGGTT
 959
TGATTTATGTCC
 960
TGTTTTTGTCGCAACTTCCATTGATTTATGTCCCTTCCCTCCC





GCAACTTCCA

CCCTGATGTA

CTTCCCTCCCCC

CCCTAAGTACATCAGGGAACCTTTCCA







CT









FSD1
NM_024333
 961
AGGCCTCCTG
 962
TGTGTGAACC
 963
CGCACCAAACAA
 964
AGGCCTCCTGTCCTTCTACAATGCCCGCACCAAACAAGTGCTG





TCCTTCTACA

TGGTCTTGAA

GTGCTGCACA

CACACTTTCAAGACCAGGTTCACACA







A









FYN
NM_002037
 965
GAAGCGCAGA
 966
CTCCTCAGAC
 967
CTGAAGCACGAC
 968
GAAGCGCAGATCATGAAGAAGCTGAAGCACGACAAGCTGGTC





TCATGAAGAA

ACCACTGCAT

AAGCTGGTCCAG

CAGCTCTATGCAGTGGTGTCTGAGGAG





G6PD
NM_000402
 969
AATCTGCCTG
 970
CGAGATGTTG
 971
CCAGCCTCAGTG
 972
AATCTGCCTGTGGCCTTGCCCGCCAGCCTCAGTGCCACTTGA





TGGCCTTG

CTGGTGACA

CCACTTGACATT

CATTCCTTGTCACCAGCAACATCTCG





GABRG2
NM_198904
 973
CCACTGTCCT
 974
GAGATCCATC
 975
CTCAGCACCATT
 976
CCACTGTCCTGACAATGACCACCCTCAGCACCATTGCCCGGA





GACAATGACC

GCTGTGACAT

GCCCGGAAAT

AATCGCTCCCCAAGGTCTCCTATGTCACAGCGATGGATCTC





GADD45A
NM_001924
 977
GTGCTGGTGA
 978
CCCGGCAAAA
 979
TTCATCTCAATG
 980
GTGCTGGTGACGAATCCACATTCATCTCAATGGAAGGATCCTG





CGAATCCA

ACAAATAAGT

GAAGGATCCTGC

CCTTAAGTCAACTTATTTGTTTTTGCCGGG









C




GADD45B
NM_015675
 981
ACCCTCGACA
 982
TGGGAGTTCA
 983
TGGGAGTTCATG
 984
ACCCTCGACAAGACCACACTTTGGGACTTGGGAGCTGGGGCT





AGACCACACT

TGGGTACAGA

GGTACAGA

GAAGTTGCTCTGTACCCATGAACTCCCA





GDF15
NM_004864
 985
CGCTCCAGAC
 986
ACAGTGGAAG
 987
TGTTAGCCAAAG
 988
CGCTCCAGACCTATGATGACTTGTTAGCCAAAGACTGCCACTG





CTATGATGAC

GACCAGGACT

ACTGCCACTGCA

CATATGAGCAGTCCTGGTCCTTCCACTGT





T











GHR
NM_000163
 989
CCACCTCCCA
 990
GGTGCGTGCC
 991
CGTGCCTCAGCC
 992
CCACCTCCCACAGGTTCAGGCGATTCCCGTGCCTCAGCCTCC





CAGGTTCA

TGTAGTCC

TCCTGAGTAGCT

TGAGTAGCTGGGACTACAGGCACGCACC





GNPTAB
NM_024312
 993
GGATTCACAT
 994
GTTCTTGCAT
 995
CCCTGCTCACAT
 996
GGATTCACATCGCGGAAAGTCCCTGCTCACATGCCTCACATGA





CGCGGAAA

AACAATCCGG

GCCTCACATGAT

TTGACCGGATTGTTATGCAAGAAC







TC









GNRH1
NM_000825
 997
AAGGGCTAAA
 998
CTGGATCTCT
 999
TCCTGTCCTTCA
1000
AAGGGCTAAATCCAGGTGTGACGGTATCTAATGATGTCCTGTC





TCCAGGTGTG

GTGGCTGGT

CTGTCCTTGCCA

CTTCACTGTCCTTGCCATCACCAGCCACAGAGATCCAG





GPM6B
NM_
1001
ATGTGCTTGG
1002
TGTAGAACAT
1003
CGCTGAGAAACC
1004
ATGTGCTTGGAGTGGCCTGGCTGGGTGTGTTTGGTTTCTCAGC



001001994

AGTGGCCT

AAACACGGGC

AAACACACCCAG

GGTGCCCGTGTTTATGTTCTACA







A









GPNMB
NM_
1005
CAGCCTCGCC
1006
TGACAAATAT
1007
CAAACAGTGCCC
1008
CAGCCTCGCCTTTAAGGATGGCAAACAGTGCCCTGATCTCCGT



001005340

TTTTAAGGA

GGCCAAGCAG

TGATCTCCGTTG

TGGCTGCTTGGCCATATTTGTCA





GPR68
NM_003485
1009
CAAGGACCAG
1010
GGTAGGGCAG
1011
CTCAGCACCGTG
1012
CAAGGACCAGATCCAGCGGCTGGTGCTCAGCACCGTGGTCAT





ATCCAGCG

GAAGCAGG

GTCATCTTCCTG

CTTCCTGGCCTGCTTCCTGCCCTACC





GPS1
NM_004127
1013
AGTACAAGCA
1014
GCAGCTCAGG
1015
CCTCCTGCTGGC
1016
AGTACAAGCAGGCTGCCAAGTGCCTCCTGCTGGCTTCCTTTGA





GGCTGCCAAG

GAAGTCACA

TTCCTTTGATCA

TCACTGTGACTTCCCTGAGCTGC





GRB7
NM_005310
1017
CCATCTGCAT
1018
GGCCACCAGG
1019
CTCCCCACCCTT
1020
CCATCTGCATCCATCTTGTTTGGGCTCCCCACCCTTGAGAAGT





CCATCTTGTT

GTATTATCTG

GAGAAGTGCCT

GCCTCAGATAATACCCTGGTGGCC





GREM1
NM_013372
1021
GTGTGGGCAA
1022
GACCTGATTT
1023
TCCACCCTCCCT
1024
GTGTGGGCAAGGACAAGCAGGATAGTGGAGTGAGAAAGGGAG





GGACAAGC

GGCCTCACC

TTCTCACTCCAC

GGTGGAGGGTGAGGCCAAATCAGGTC





GSK3B
NM_002093
1025
GACAAGGACG
1026
TTGTGGCCTG
1027
CCAGGAGTTGCC
1028
GACAAGGACGGCAGCAAGGTGACAACAGTGGTGGCAACTCCT





GCAGCAAG

TCTGGACC

ACCACTGTTGTC

GGGCAGGGTCCAGACAGGCCACAA





GSN
NM_000177
1029
CTTCTGCTAA
1030
GGCTCAAAGC
1031
ACCCAGCCAATC
1032
CTTCTGCTAAGCGGTACATCGAGACGGACCCAGCCAATCGGG





GCGGTACATC

CTTGCTTCAC

GGGATCGGC

ATCGGCGGACGCCCATCACCGTGGTGAAGCAAGGCTTTGAGC





GA





C





GSTM1
NM_000561
1033
AAGCTATGAG
1034
GGCCCAGCTT
1035
TCAGCCACTGGC
1036
AAGCTATGAGGAAAAGAAGTACACGATGGGGGACGCTCCTGA





GAAAAGAAGT

GAATTTTTCA

TTCTGTCATAAT

TTATGACAGAAGCCAGTGGCTGAATGAAAAATTCAAGCTGGGC





ACACGAT



CAGGAG

C





GSTM2
NM_000848
1037
CTGCAGGCAC
1038
CCAAGAAACC
1039
CTGAAGCTCTAC
1040
CTGCAGGCACTCCCTGAAATGCTGAAGCTCTACTCACAGTTTC





TCCCTGAAAT

ATGGCTGCTT

TCACAGTTTCTG

TGGGGAAGCAGCCATGGTTTCTTGG









GG







HDAC1
NM_004964
1041
CAAGTACCAC
1042
GCTTGCTGTA
1043
TTCTTGCGCTCC
1044
CAAGTACCACAGCGATGACTACATTAAATTCTTGCGCTCCATC





AGCGATGACT

CTCCGACATG

ATCCGTCCAGA

CGTCCAGATAACATGTCGGAGTACAGCAAGC





ACATTAA

TT









HDAC9
NM_178423
1045
AACCAGGCAG
1046
CTCTGTCTTC
1047
CCCCCTGAAGCT
1048
AACCAGGCAGTCACCTTGAGGAAGCAGAGGAAGAGCTTCAGG





TCACCTTGAG

CTGCATCGC

CTTCCTCTGCTT

GGGACCAGGCGATGCAGGAAGACAGAG





HGD
NM_000187
1049
CTCAGGTCTG
1050
TTATTGGTGC
1051
CTGAGCAGCTCT
1052
CTCAGGTCTGCCCCTACAATCTCTATGCTGAGCAGCTCTCAGG





CCCCTACAAT

TCCGTGGAC

CAGGATCGGCTT

ATCGGCTTTCACTTGTCCACGGAGCACCAATAA





HIP1
NM_005338
1053
CTCAGAGCCC
1054
GGGTTTCCCT
1055
CGACTCACTGAC
1056
CTCAGAGCCCCACCTGAGCCTGCCGACTCACTGACCGAGGCC





CACCTGAG

GCCATACTG

CGAGGCCTGTAA

TGTAAGCAGTATGGCAGGGAAACCC





HIRIP3
NM_003609
1057
GGATGAGGAA
1058
TCCCTAGCTG
1059
CCATTGCTCCTG
1060
GGATGAGGAAAAGGGGGATTGGAAACCCAGAACCAGGAGCAA





AAGGGGGAT

ACTTTCTCCG

GTTCTGGGTTTC

TGGCCGGAGAAAGTCAGCTAGGGA





HK1
NM_000188
1061
TACGCACAGA
1062
GAGAGAAGTG
1063
TAAGAGTCCGGG
1064
TACGCACAGAGGCAAGCAGCTAAGAGTCCGGGATCCCCAGCC





GGCAAGCA

CTGGAGAGGC

ATCCCCAGCCTA

TACTGCCTCTCCAGCACTTCTCTC





HLA-G
NM_002127
1065
CCATCCCCAT
1066
CCGCAGCTCC
1067
CTGCAAGGACAA
1068
CCTGCGCGGCTACTACAACCAGAGCGAGGCCAGTTCTCACAC





CATGGGTATC

AGTGACTACA

CCAGGCCAGCAA

CCTCCAGTGGATGATTGGCTGCGACCTG





HLF
NM_002126
1069
CACCCTGCAG
1070
GGTACCTAGG
1071
TAAGTGATCTGC
1072
CACCCTGCAGGTGTCTGAGACTAAGTGATCTGCCCTCCAGGT





GTGTCTGAG

AGCAGAAGGT

CCTCCAGGTGGC

GGCGATCACCTTCTGCTCCTAGGTACC







GA









HNF1B
NM_000458
1073
TCCCAGCATC
1074
CGTACCAGGT
1075
CCCCTATGAAGA
1076
TCCCAGCATCTCAACAAGGGCACCCCTATGAAGACCCAGAAG





TCAACAAGG

GTACAGAGCG

CCCAGAAGCGTG

CGTGCCGCTCTGTACACCTGGTACG





HPS1
NM_000195
1077
GCGGAAGCTG
1078
TTCGGATAAG
1079
CAGTCACCAGCC
1080
GCGGAAGCTGTATGTGCTCAAGTACCTGTTTGAAGTGCACTTT





TATGTGCTC

ATGACCGTCC

CAAAGTGCACTT

GGGCTGGTGACTGTGGACGGTCATCTTATCCGAA





HRAS
NM_005343
1081
GGACGAATAC
1082
GCACGTCTCC
1083
ACCACCTGCTTC
1084
GGACGAATACGACCCCACTATAGAGGATTCCTACCGGAAGCA





GACCCCACT

CCATCAAT

CGGTAGGAATCC

GGTGGTCATTGATGGGGAGACGTGC





HSD17B10
NM_004493
1085
CCAGCGAGTT
1086
ATCTCACCAG
1087
TCATGGGCACCT
1088
CCACCAGACAAGACCGATTCGCTGGCCTCCATTTCTTCAACCC





CTTGATGTGA

CCACCAGG

TCAATGTGATCC

AGTGCCTGTCATGAAACTTGTGG





HSD17B2
NM_002153
1089
GCTTTCCAAG
1090
TGCCTGCGAT
1091
AGTTGCTTCCAT
1092
GCTTTCCAAGTGGGGAATTAAAGTTGCTTCCATCCAACCTGGA





TGGGGAATTA

ATTTGTTAGG

CCAACCTGGAGG

GGCTTCCTAACAAATATCGCAGGCA





HSD17B3
NM_000197
1093
GGGACGTCCT
1094
TGGAGAATCT
1095
CTTCATCCTCAC
1096
GGGACGTCCTGGAACAGTTCTTCATCCTCACAGGGCTGCTGG





GGAACAGT

CACGCACTTC

AGGGCTGCTGGT

TGTGCCTGGCCTGCCTGGCGAAGTGCGTGAGATTCTCCA





HSD17B4
NM_000414
1097
CGGGAAGCTT
1098
ACCTCAGGCC
1099
AGGCGGCGTCCT
1100
CGGGAAGCTTCAGAGTACCTTTGTATTTGAGGAAATAGGACGC





CAGAGTACCT

CAATATCCTT

ATTTCCTCAAAT

CGCCTAAAGGATATTGGGCCTGAGGT





T











HSD3B2
NM_000198
1101
GCCTTCCTTT
1102
GGAGTAAATT
1103
ACTTCCAGCAGG
1104
GCCTTCCTTTAACCCTGATGTACTGGATTGGCTTCCTGCTGGA





AACCCTGATG

GGGCTGAGTA

AAGCCAATCCAG

AGTAGTGAGCTTCCTACTCAGCCCAATTTACTCC







GG









HSP90AB1
NM_007355
1105
GCATTGTGAC
1106
GAAGTGCCTG
1107
ATCCGCTCCATA
1108
GCATTGTGACCAGCACCTACGGCTGGACAGCCAATATGGAGC





CAGCACCTAC

GGCTTTCAT

TTGGCTGTCCAG

GGATCATGAAAGCCCAGGCACTTC





HSPA5
NM_005347
1109
GGCTAGTAGA
1110
GGTCTGCCCA
1111
TAATTAGACCTA
1112
GGCTAGTAGAACTGGATCCCAACACCAAACTCTTAATTAGACC





ACTGGATCCC

AATGCTTTTC

GGCCTCAGCTGC

TAGGCCTCAGCTGCACTGCCCGAAAAGCATTTGGGCAGACC





AACA



ACTGCC







HSPA8
NM_006597
1113
CCTCCCTCTG
1114
GCTACATCTA
1115
CTCAGGGCCCAC
1116
CCTCCCTCTGGTGGTGCTTCCTCAGGGCCCACCATTGAAGAG





GTGGTGCTT

CACTTGGTTG

CATTGAAGAGGT

GTTGATTAAGCCAACCAAGTGTAGATGTAGC







GCTTAA

TG







HSPB1
NM_001540
1117
CCGACTGGAG
1118
ATGCTGGCTG
1119
CGCACTTTTCTG
1120
CCGACTGGAGGAGCATAAAAGCGCAGCCGAGCCCAGCGCCC





GAGCATAAA

ACTCTGCTC

AGCAGACGTCCA

CGCACTTTTCTGAGCAGACGTCCAGAGCAGAGTCAGCCAGCA











T





HSPB2
NM_001541
1121
CACCACTCCA
1122
TGGGACCAAA
1123
CACCTTTCCCTT
1124
CACCACTCCAGAGGTAGCAGCATCCTTGGGGGAAGGGAAAGG





GAGGTAGCAG

CCATACATTG

CCCCCAAGGAT

TGCATGGTCCACAATGTATGGTTTGGTCCCA





HSPE1
NM_002157
1125
GCAAGCAACA
1126
CCAACTTTCA
1127
TCTCCACCCTTT
1128
GCAAGCAACAGTAGTCGCTGTTGGATCGGGTTCTAAAGGAAA





GTAGTCGCTG

CGCTAACTGG

CCTTTAGAACCC

GGGTGGAGAGATTCAACCAGTTAGCGTGAAAGTTGG







T

G







HSPG2
NM_005529
1129
GAGTACGTGT
1130
CTCAATGGTG
1131
CAGCTCCGTGCC
1132
GAGTACGTGTGCCGAGTGTTGGGCAGCTCCGTGCCTCTAGAG





GCCGAGTGTT

ACCAGGACA

TCTAGAGGCCT

GCCTCTGTCCTGGTCACCATTGAG





ICAM1
NM_000201
1133
GCAGACAGTG
1134
CTTCTGAGAC
1135
CCGGCGCCCAAC
1136
GCAGACAGTGACCATCTACAGCTTTCCGGCGCCCAACGTGATT





ACCATCTACA

CTCTGGCTTC

GTGATTCT

CTGACGAAGCCAGAGGTCTCAGAAG





GCTT

GT









IER3
NM_003897
1137
GTACCTGGTG
1138
GCGTCTCCGC
1139
TCAAGTTGCCTC
1140
GTACCTGGTGCGCGAGAGCGTATCCCCAACTGGGACTTCCGA





CGCGAGAG

TGTAGTGTT

GGAAGTCCCAGT

GGCAACTTGAACTCAGAACACTACAGCGGAGACGC





IFI30
NM_006332
1141
ATCCCATGAA
1142
GCACCATTCT
1143
AAAATTCCACCC
1144
ATCCCATGAAGCCCAGATACACAAAATTCCACCCCATGATCAA





GCCCAGATAC

TAGTGGAGCA

CATGATCAAGAA

GAATCCTGCTCCACTAAGAATGGTGC









TCC







IFIT1
NM_001548
1145
TGACAACCAA
1146
CAGTCTGCCC
1147
AAGTTGCCCCAG
1148
TGACAACCAAGCAAATGTGAGGAGTCTGGTGACCTGGGGCAA





GCAAATGTGA

ATGTGGTAAT

GTCACCAGACTC

CTTTGCCTGGATGTATTACCACATGGGCAGACTG





IFNG
NM_000619
1149
GCTAAAACAG
1150
CAACCATTAC
1151
TCGACCTCGAAA
1152
GCTAAAACAGGGAAGCGAAAAAGGAGTCAGATGCTGTTTCGA





GGAAGCGAAA

TGGGATGCTC

CAGCATCTGACT

GGTCGAAGAGCATCCCAGTAATGGTTG









CC







IGF1
NM_000618
1153
TCCGGAGCTG
1154
CGGACAGAGC
1155
TGTATTGCGCAC
1156
TCCGGAGCTGTGATCTAAGGAGGCTGGAGATGTATTGCGCAC





TGATCTAAGG

GAGCTGACTT

CCCTCAAGCCTG

CCCTCAAGCCTGCCAAGTCAGCTCGCTCTGTCCG





A











IGF1R
NM_000875
1157
GCATGGTAGC
1158
TTTCCGGTAA
1159
CGCGTCATACCA
1160
GCATGGTAGCCGAAGATTTCACAGTCAAAATCGGAGATTTTGG





CGAAGATTTC

TAGTCTGTCT

AAATCTCCGATT

TATGACGCGAGATATCTATGAGACAGACTATTACCGGAAA





A

CATAGATATC

TTGA







IGF2
NM_000612
1161
CCGTGCTTCC
1162
TGGACTGCTT
1163
TACCCCGTGGGC
1164
CCGTGCTTCCGGACAACTTCCCCAGATACCCCGTGGGCAAGT





GGACAACTT

CCAGGTGTCA

AAGTTCTTCCAA

TCTTCCAATATGACACCTGGAAGCAGTCCA





IGFBP2
NM_000597
1165
GTGGACAGCA
1166
CCTTCATACC
1167
CTTCCGGCCAGC
1168
GTGGACAGCACCATGAACATGTTGGGCGGGGGAGGCAGTGCT





CCATGAACA

CGACTTGAGG

ACTGCCTC

GGCCGGAAGCCCCTCAAGTCGGGTATGAAGG





IGFBP3
NM_000598
1169
ACATCCCAAC
1170
CCACGCCCTT
1171
ACACCACAGAAG
1172
ACATCCCAACGCATGCTCCTGGAGCTCACAGCCTTCTGTGGTG





GCATGCTC

GTTTCAGA

GCTGTGAGCTCC

TCATTTCTGAAACAAGGGCGTGG





IGFBP5
NM_000599
1173
TGGACAAGTA
1174
CGAAGGTGTG
1175
CCCGTCAACGTA
1176
TGGACAAGTACGGGATGAAGCTGCCAGGCATGGAGTACGTTG





CGGGATGAAG

GCACTGAAAG

CTCCATGCCTGG

ACGGGGACTTTCAGTGCCACACCTTCG





CT

T









IGFBP6
NM_002178
1177
TGAACCGCAG
1178
GTCTTGGACA
1179
ATCCAGGCACCT
1180
TGAACCGCAGAGACCAACAGAGGAATCCAGGCACCTCTACCA





AGACCAACAG

CCCGCAGAAT

CTACCACGCCCT

CGCCCTCCCAGCCCAATTCTGCGGGTGTCCAAGAC









C







IL10
NM_000572
1181
CTGACCACGC
1182
CCAAGCCCAG
1183
TTGAGCTGTTTT
1184
CTGACCACGCTTTCTAGCTGTTGAGCTGTTTTCCCTGACCTCC





TTTCTAGCTG

AGACAAGATA

CCCTGACCTCCC

CTCTAATTTATCTTGTCTCTGGGCTTGG







A









IL11
NM_000641
1185
TGGAAGGTTC
1186
TCTTGACCTT
1187
CCTGTGATCAAC
1188
TGGAAGGTTCCACAAGTCACCCTGTGATCAACAGTACCCGTAT





CACAAGTCAC

GCAGCTTTGT

AGTACCCGTATG

GGGACAAAGCTGCAAGGTCAAGA









GG







IL17A
NM_002190
1189
TCAAGCAACA
1190
CAGCTCCTTT
1191
TGGCTTCTGTCT
1192
TCAAGCAACACTCCTAGGGCCTGGCTTCTGTCTGATCAAGGCA





CTCCTAGGGC

CTGGGTTGTG

GATCAAGGCACC

CCACACAACCCAGAAAGGAGCTG





IL1A
NM_000575
1193
GGTCCTTGGT
1194
GGATGGAGCT
1195
TCTCCACCCTGG
1196
GGTCCTTGGTAGAGGGCTACTTTACTGTAACAGGGCCAGGGT





AGAGGGCTAC

TCAGGAGAGA

CCCTGTTACAGT

GGAGAGTTCTCTCCTGAAGCTCCATCC





TT











IL1B
NM_000576
1197
AGCTGAGGAA
1198
GGAAAGAAGG
1199
TGCCCACAGACC
1200
AGCTGAGGAAGATGCTGGTTCCCTGCCCACAGACCTTCCAGG





GATGCTGGTT

TGCTCAGGTC

TTCCAGGAGAAT

AGAATGACCTGAGCACCTTCTTTCC





IL2
NM_000586
1201
ACCTCAACTC
1202
CACTGTTTGT
1203
TGCAACTCCTGT
1204
ACCTCAACTCCTGCCACAATGTACAGGATGCAACTCCTGTCTT





CTGCCACAAT

GACAAGTGCA

CTTGCATTGCAC

GCATTGCACTAAGTCTTGCACTTGTCACAAACAGTG







AG









IL6
NM_000600
1205
CCTGAACCTT
1206
ACCAGGCAAG
1207
CCAGATTGGAAG
1208
CCTGAACCTTCCAAAGATGGCTGAAAAAGATGGATGCTTCCAA





CCAAAGATGG

TCTCCTCATT

CATCCATCTTTT

TCTGGATTCAATGAGGAGACTTGCCTGGT









TCA







IL6R
NM_000565
1209
CCAGCTTATC
1210
CTGGCGTAGA
1211
CCTTTGGCTTCA
1212
CCAGCTTATCTCAGGGGTGTGCGGCCTTTGGCTTCACGGAAG





TCAGGGGTGT

ACCTTCCG

CGGAAGAGCCTT

AGCCTTGCGGAAGGTTCTACGCCAG





IL6ST
NM_002184
1213
GGCCTAATGT
1214
AAAATTGTGC
1215
CATATTGCCCAG
1216
GGCCTAATGTTCCAGATCCTTCAAAGAGTCATATTGCCCAGTG





TCCAGATCCT

CTTGGAGGAG

TGGTCACCTCAC

GTCACCTCACACTCCTCCAAGGCACAATTTT









A







IL8
NM_000584
1217
AAGGAACCAT
1218
ATCAGGAAGG
1219
TGACTTCCAAGC
1220
AAGGAACCATCTCACTGTGTGTAAACATGACTTCCAAGCTGGC





CTCACTGTGT

CTGCCAAGAG

TGGCCGTGGC

CGTGGCTCTCTTGGCAGCCTTCCTGAT





GTAAAC











ILF3
NM_004516
1221
GACACGCCAA
1222
CTCAAGACCC
1223
ACACAAGACTTC
1224
GACACGCCAAGTGGTTCCAGGCCAGAGCCAACGGGCTGAAGT





GTGGTTCC

GGATCACAA

AGCCCGTTGGCT

CTTGTGTCATTGTGATCCGGGTCTTGAG





ILK
NM_
1225
CTCAGGATTT
1226
AGGAGCAGGT
1227
ATGTGCTCCCAG
1228
CTCAGGATTTTCTCGCATCCAAATGTGCTCCCAGTGCTAGGTG



001014794

TCTCGCATCC

GGAGACTGG

TGCTAGGTGCCT

CCTGCCAGTCTCCACCTGCTCCT





IMMT
NM_006839
1229
CTGCCTATGC
1230
GCTTTTCTGG
1231
CAACTGCATGGC
1232
CTGCCTATGCCAGACTCAGAGGAATCGAACAGGCTGTTCAGA





CAGACTCAGA

CTTCCTCTTC

TCTGAACAGCCT

GCCATGCAGTTGCTGAAGAGGAAGCCAGAAAAGC





ING5
NM_032329
1233
CCTACAGCAA
1234
CATCTCGTAG
1235
CCAGCTGCACTT
1236
CCTACAGCAAGTGCAAGGAATACAGTGACGACAAAGTGCAGC





GTGCAAGGAA

GTCTGCATGG

TGTCGTCACTGT

TGGCCATGCAGACCTACGAGATG





INHBA
NM_002192
1237
GTGCCCGAGC
1238
CGGTAGTGGT
1239
ACGTCCGGGTCC
1240
GTGCCCGAGCCATATAGCAGGCACGTCCGGGTCCTCACTGTC





CATATAGCA

TGATGACTGT

TCACTGTCCTTC

CTTCCACTCAACAGTCATCAACCACTACCG







TGA

C







INSL4
NM_002195
1241
CTGTCATATT
1242
CAGATTCCAG
1243
TGAGAAGACATT
1244
CTGTCATATTGCCCCATGCCTGAGAAGACATTCACCACCACCC





GCCCCATGC

CAGCCACC

CACCACCACCCC

CAGGAGGGTGGCTGCTGGAATCTG





ITGA1
NM_181501
1245
GCTTCTTCTG
1246
CCTGTAGATA
1247
TTGCTGGACAGC
1248
GCTTCTTCTGGAGATGTGCTCTATATTGCTGGACAGCCTCGGT





GAGATGTGCT

ATGACCTGGC

CTCGGTACAATC

ACAATCATACAGGCCAGGTCATTATCTACAGG





CT

CT









ITGA3
NM_002204
1249
CCATGATCCT
1250
GAAGCTTTGT
1251
CACTCCAGACCT
1252
CCATGATCCTCACTCTGCTGGTGGACTATACACTCCAGACCTC





CACTCTGCTG

AGCCGGTGAT

CGCTTAGCATGG

GCTTAGCATGGTAAATCACCGGCTACAAAGCTTC





ITGA4
NM_000885
1253
CAACGCTTCA
1254
GTCTGGCCGG
1255
CGATCCTGCATC
1256
CAACGCTTCAGTGATCAATCCCGGGGCGATTTACAGATGCAG





GTGATCAATC

GATTCTTT

TGTAAATCGCCC

GATCGGAAAGAATCCCGGCCAGAC





C











ITGA5
NM_002205
1257
AGGCCAGCCC
1258
GTCTTCTCCA
1259
TCTGAGCCTTGT
1260
AGGCCAGCCCTACATTATCAGAGCAAGAGCCGGATAGAGGAC





TACATTATCA

CAGTCCAGCA

CCTCTATCCGGC

AAGGCTCAGATCTTGCTGGACTGTGGAGAAGAC





ITGA6
NM_000210
1261
CAGTGACAAA
1262
GTTTAGCCTC
1263
TCGCCATCTTTT
1264
CAGTGACAAACAGCCCTTCCAACCCAAGGAATCCCACAAAAGA





CAGCCCTTCC

ATGGGCGTC

GTGGGATTCCTT

TGGCGATGACGCCCATGAGGCTAAAC





ITGA7
NM_002206
1265
GATATGATTG
1266
AGAACTTCCA
1267
CAGCCAGGACCT
1268
GATATGATTGGTCGCTGCTTTGTGCTCAGCCAGGACCTGGCCA





GTCGCTGCTT

TTCCCCACCA

GGCCATCCG

TCCGGGATGAGTTGGATGGTGGGGAATGGAAGTTCT





TG

T









ITGAD
NM_005353
1269
GAGCCTGGTG
1270
ACTGTCAGGA
1271
CAACTGAAAGGC
1272
GAGCCTGGTGGATCCCATCGTCCAACTGAAAGGCCTGACGTT





GATCCCAT

TGCCCGTG

CTGACGTTCACG

CACGGCCACGGGCATCCTGACAGT





ITGB3
NM_000212
1273
ACCGGGAGCC
1274
CCTTAAGCTC
1275
AAATACCTGCAA
1276
ACCGGGGAGCCCTACATGACGAAAATACCTGCAACCGTTACT





CTACATGAC

TTTCACTGAC

CCGTTACTGCCG

GCCGTGACGAGATTGAGTCAGTGAAAGAGCTTAAGG







TCAATCT

TGAC







ITGB4
NM_000213
1277
CAAGGTGCCC
1278
GCGCACACCT
1279
CACCAACCTGTA
1280
CAAGGTGCCCTCAGTGGAGCTCACCAACCTGTACCCGTATTG





TCAGTGGA

TCATCTCAT

CCCGTATTGCGA

CGACTATGAGATGAAGGTGTGCGC





ITGB5
NM_002213
1281
TCGTGAAAGA
1282
GGTGAACATC
1283
TGCTATGTTTCT
1284
TCGTGAAAGATGACCAGGAGGCTGTGCTATGTTTCTACAAAAC





TGACCAGGAG

ATGACGCAGT

ACAAAACCGCCA

CGCCAAGGACTGCGTCATGATGTTCACC









AGG







ITPR1
NM_002222
1285
GAGGAGGTGT
1286
GTAATCCCAT
1287
CCATCCTAACGG
1288
GAGGAGGTGTGGGTGTTCCGCTTCCATCCTAACGGAACGAGC





GGGTGTTCC

GTCCGCGA

AACGAGCTCCCT

TCCCTCTTCGCGGACATGGGATTAC





ITPR3
NM_002224
1289
TTGCCATCGT
1290
ATGGAGCTGG
1291
TCCAGGTCTCGG
1292
TTGCCATCGTGTCAGTGCCCGTGTCTGAGATCCGAGACCTGG





GTCAGTGC

CGTCATTG

ATCTCAGACACG

ACTTTGCCAATGACGCCAGCTCCAT





ITSN1
NM_003024
1293
TAACTGGGAT
1294
CTCTGCCTTA
1295
AGCCCTCTCTCA
1296
TAACTGGGATGCATGGGCAGCCCAGCCCTCTCTCACCGTTCC





GCATGGGC

ACTGGCCG

CCGTTCCAAGTG

AAGTGCCGGCCAGTTAAGGCAGAG





JAG1
NM_000214
1297
TGGCTTACAC
1298
GCATAGCTGT
1299
ACTCGATTTCCC
1300
TGGCTTACACTGGCAATGGTAGTTTCTGTGGTTGGCTGGGAAA





TGGCAATGG

GAGATGCGG

AGCCAACCACAG

TCGAGTGCCGCATCTCACAGCTATGC





JUN
NM_002228
1301
GACTGCAAAG
1302
TAGCCATAAG
1303
CTATGACGATGC
1304
GACTGCAAAGATGGAAACGACCTTCTATGACGATGCCCTCAAC





ATGGAAACGA

GTCCGCTCTC

CCTCAACGCCTC

GCCTCGTTCCTCCCGTCCGAGAGCGGACCTTATGGCTA





JUNB
NM_002229
1305
CTGTCAGCTG
1306
AGGGGGTGTC
1307
CAAGGGACACGC
1308
CTGTCAGCTGCTGCTTGGGGTCAAGGGACACGCCTTCTGAAC





CTGCTTGG

CGTAAAGG

CTTCTGAACGT

GTCCCCTGCCCCTTTACGGACACCCCCT





KCNN2
NM_021614
1309
TGTGCTATTC
1310
GGGCATAGGA
1311
TTATACATTCAC
1312
TGTGCTATTCATCCCATACCTGGGAATTATACATTCACATGGA





ATCCCATACC

GAAGGCAAG

ATGGACGGCCCG

CGGCCCGGCTTGCCTTCTCCTATGCCC





TG











KCTD12
NM_138444
1313
AGCAGTTACT
1314
TGGAGACCTG
1315
ACTCTTAGGCGG
1316
AGCAGTTACTGGCAAGAGGGAGAAAGGACGCTGCCGCCTAAG





GGCAAGAGGG

AGCAGCCT

CAGCGTCCTTTC

AGTGCAAGGCTGCTCAGGTCTCCA





KHDRBS3
NM_006558
1317
CGGGCAAGAA
1318
CTGTAGACGC
1319
CAAGACACAAGG
1320
CGGGCAAGAAGAGTGGACTAACTCAAGACACAAGGCACCTTC





GAGTGGAC

CCTTTGCTGT

CACCTTCAGCGA

AGCGAGGACAGCAAAGGGCGTCTACAG





KIAA0196
NM_014846
1321
CAGACACCAG
1322
AACATTGTGA
1323
TCCCCAGTGTCC
1324
CAGACACCAGCTCTGAGGCCAGTTAATCATCCCCAGTGTCCAG





CTCTGAGGC

GGCGGACC

AGGCACAGAGTA

GCACAGAGTAGTCGGTCCGCCTCACAATGTT





KIAA0247
NM_014734
1325
CCGTGGGACA
1326
GAAGCAAGTC
1327
TCCGCTAGTGAT
1328
CCGTGGGACATGGAGTGTTCCTTCCGCTAGTGATCCTTTGCAC





TGGAGTGT

CGTCTCCAAG

CCTTTGCACCCT

CCTGCTTGGAGACGGACTTGCTTC





KIF4A
NM_012310
1329
AGAGCTGGTC
1330
GCTGGTCTTG
1331
CAGGTCAGCAAA
1332
AGAGCTGGTCTCCTCCAAAATACAGGTCAGCAAACTTGAAAGC





TCCTCCAAAA

CTCTGTTTCA

CTTGAAAGCAGC

AGCCTGAAACAGAGCAAGACCAGC









C







KIT
NM_000222
1333
GAGGCAACTG
1334
GGCACTCGGC
1335
TTACAGCGACAG
1336
GAGGCAACTGCTTATGGCTTAATTAAGTCAGATGCGGCCATGA





CTTATGGCTT

TTGAGCAT

TCATGGCCGCAT

CTGTCGCTGTAAAGATGCTCAAGCCGAGTGCC





AATTA











KLC1
NM_182923
1337
AGTGGCTACG
1338
TGAGCCACAG
1339
CAACACGCAGCA
1340
AGTGGCTACGGGATGAACTGGCCAACACGCAGCAGAAACTGC





GGATGAACTG

ACTGCTCACT

GAAACTGCAGAA

AGAAGAGTGAGCAGTCTGTGGCTCA





KLF6
NM_001300
1341
CACGAGACCG
1342
GCTCTAGGCA
1343
AGTACTCCTCCA
1344
CACGAGACCGGCTACTTCTCGGCGCTGCCGTCTCTGGAGGAG





GCTACTTCTC

GGTCTGTTGC

GAGACGGCAGCG

TACTGGCAACAGACCTGCCTAGAGC





KLK1
NM_002257
1345
AACACAGCCC
1346
CCAGGAGGCT
1347
TCAGTGAGAGCT
1348
AACACAGCCCAGTTTGTTCATGTCAGTGAGAGCTTCCCACACC





AGTTTGTTCA

CATGTTGAAG

TCCCACACCCTG

CTGGCTTCAACATGAGCCTCCTGG





KLK10
NM_002776
1349
GCCCAGAGGC
1350
CAGAGGTTTG
1351
CCTCTTCCTCCC
1352
GCCCAGAGGCTCCATCGTCCATCCTCTTCCTCCCCAGTCGGCT





TCCATCGT

AACAGTGCAG

CAGTCGGCTGA

GAACTCTCCCCTTGTCTGCACTGTTCAAACCTCTG







ACA









KLK11
NM_006853
1353
CACCCCGGCT
1354
CATCTTCACC
1355
CCTCCCCAACAA
1356
CACCCCGGCTTCAACAACAGCCTCCCCAACAAAGACCACCGC





TCAACAAC

AGCATGATGT

AGACCACCGCA

AATGACATCATGCTGGTGAAGATG







CA









KLK14
NM_022046
1357
CCCCTAAAAT
1358
CTCATCCTCT
1359
CAGCACTTCAAG
1360
CCCCTAAAATGTTCCTCCTGCTGACAGCACTTCAAGTCCTGGC





GTTCCTCCTG

TGGCTCTGTG

TCCTGGCTATAG

TATAGCCATGACACAGAGCCAAGAGGATGAG









CCA







KLK2
NM_005551
1361
AGTCTCGGAT
1362
TGTACACAGC
1363
TTGGGAATGCTT
1364
AGTCTCGGATTGTGGGAGGCTGGGAGTGTGAGAAGCATTCCC





TGTGGGAGG

CACCTGCC

CTCACACTCCCA

AACCCTGGCAGGTGGCTGTGTACA





KLK3
NM_001648
1365
CCAAGCTTAC
1366
AGGGTGAGGA
1367
ACCCACATGGTG
1368
CCAAGCTTACCACCTGCACCCGGAGAGCTGTGTCACCATGTG





CACCTGCAC

AGACAACCG

ACACAGCTCTCC

GGTCCCGGTTGTCTTCCTCACCCT





KLRK1
NM_007360
1369
TGAGAGCCAG
1370
ATCCTGGTCC
1371
TGTCTCAAAATG
1372
TGAGAGCCAGGCTTCTTGTATGTCTCAAAATGCCAGCCTTCTG





GCTTCTTGTA

TCTTTGCTGT

CCAGCCTTCTGA

AAAGTATACAGCAAAGAGGACCAGGAT









A







KPNA2
NM_002266
1373
TGATGGTCCA
1374
AAGCTTCACA
1375
ACTCCTGTTTTC
1376
TGATGGTCCAAATGAACGAATTGGCATGGTGGTGAAAACAGGA





AATGAACGAA

AGTTGGGGC

ACCACCATGCCA

GTTGTGCCCCAACTTGTGAAGCTT





KRT1
NM_006121
1377
TGGACAACAA
1378
TATCCTCGTA
1379
CCTCAGCAATGA
1380
TGGACAACAACCGCAGTCTCGACCTGGACAGCATCATTGCTGA





CCGCAGTC

CTGGGCCTTG

TGCTGTCCAGGT

GGTCAAGGCCCAGTACGAGGATA





KRT15
NM_002275
1381
GCCTGGTTCT
1382
CTTGCTGGTC
1383
TGAACAAAGAGG
1384
GCCTGGTTCTTCAGCAAGACTGAGGAGCTGAACAAAGAGGTG





TCAGCAAGAC

TGGATCATTT

TGGCCTCCAACA

GCCTCCAACACAGAAATGATCCAGACCAGCAAG







C









KRT18
NM_000224
1385
AGAGATCGAG
1386
GGCCTTTTAC
1387
TGGTTCTTCTTC
1388
AGAGATCGAGGCTCTCAAGGAGGAGCTGCTCTTCATGAAGAA





GCTCTCAAGG

TTCCTCTTCG

ATGAAGAGCAGC

GAACCACGAAGAGGAAGTAAAAGGCC









TCC







KRT2
NM_000423
1389
CCAGTGACGC
1390
GGGCATGGCT
1391
ACCTAGACAGCA
1392
CCAGTGACGCCTCTGTGTTCTGGGGCGGAATCTGTGCTGTCTA





CTCTGTGTT

AGAAGCAC

CAGATTCCGCCC

GGTTTGTGCTTCTAGCCATGCCC





KRT5
NM_000424
1393
TCAGTGGAGA
1394
TGCCATATCC
1395
CCAGTCAACATC
1396
TCAGTGGAGAAGGAGTTGGACCAGTCAACATCTCTGTTGTCAC





AGGAGTTGGA

AGAGGAAACA

TCTGTTGTCACA

AAGCAGTGTTTCCTCTGGATATGGCA









AGCA







KRT75
NM_004693
1397
TCAAAGTCAG
1398
ACGTCCTTTT
1399
TTCATTCTCAGC
1400
TCAAAGTCAGGTACGAAGATGAAATTAACAAGCGCACAGCTGC





GTACGAAGAT

TCAGGGCTAC

AGCTGTGCGCTT

TGAGAATGAATTTGTAGCCCTGAAAAAGGACGT





GAAATT

AA

GT







KRT76
NM_015848
1401
ATCTCCAGAC
1402
TCAGGGAATT
1403
TCTGGGCTTCAG
1404
ATCTCCAGACTGCTGGTTCCCAGGGAACCCTCCCTACATCTGG





TGCTGGTTCC

AGGGGACAGA

ATCCTGACTCCC

GCTTCAGATCCTGACTCCCTTCTGTCCCCTAATTCCCTGA





KRT8
NM_002273
1405
GGATGAAGCT
1406
CATATAGCTG
1407
CGTCGGTCAGCC
1408
GGATGAAGCTTACATGAACAAGGTAGAGCTGGAGTCTCGCCT





TACATGAACA

CCTGAGGAAG

CTTCCAGGC

GGAAGGGCTGACCGACGAGATCAACTTCCTCAGGCAGCTATA





AGGTAGA

TTGAT



TG





L1CAM
NM_000425
1409
CTTGCTGGCC
1410
TGATTGTCCG
1411
ATCTACGTTGTC
1412
CTTGCTGGCCAATGCCTACATCTACGTTGTCCAGCTGCCAGCC





AATGCCTA

CAGTCAGG

CAGCTGCCAGCC

AAGATCCTGACTGCGGACAATCA





LAG3
NM_002286
1413
GCCTTAGAGC
1414
CGGTTCTTGC
1415
TCTATCTTGCTC
1416
GCCTTAGAGCAAGGGATTCACCCTCCGCAGGCTCAGAGCAAG





AAGGGATTCA

TCCAGCTC

TGAGCCTGCGGA

ATAGAGGAGCTGGAGCAAGAACCG





LAMA3
NM_000227
1417
CCTGTCACTG
1418
TGGGTTACTG
1419
ATTCAGACTGAC
1420
CCTGTCACTGAAGCCTTGGAAGTCCAGGGGCCTGTCAGTCTG





AAGCCTTGG

GTCAGGACAA

AGGCCCCTGGAC

AATGGTTGTCCTGACCAGTAACCCA







C









LAMA4
NM_002290
1421
GATGCACTGC
1422
CAGAGGATAC
1423
CTCTCCATCGAG
1424
GATGCACTGCGGTTAGCAGCGCTCTCCATCGAGGAAGGCAAA





GGTTAGCAG

GCTCAGCACC

GAAGGCAAATCC

TCCGGGGTGCTGAGCGTATCCTCTG





LAMA5
NM_005560
1425
CTCCTGGCCA
1426
ACACAAGGCC
1427
CTGTTCCTGGAG
1428
CTCCTGGCCAACAGCACTGCACTAGAAGAGGCCATGCTCCAG





ACAGCACT

CAGCCTCT

CATGGCCTCTTC

GAACAGCAGAGGCTGGGCCTTGTGT





LAMB1
NM_002291
1429
CAAGGAGACT
1430
CGGCAGAACT
1431
CAAGTGCCTGTA
1432
CAAGGAGACTGGGAGGTGTCTCAAGTGCCTGTACCACACGGA





GGGAGGTGTC

GACAGTGTTC

CCACACGGAAGG

AGGGGAACACTGTCAGTTCTGCCG





LAMB3
NM_000228
1433
ACTGACCAAG
1434
GTCACACTTG
1435
CCACTCGCCATA
1436
ACTGACCAAGCCTGAGACCTACTGCACCCAGTATGGCGAGTG





CCTGAGACCT

CAGCATTTCA

CTGGGTGCAGT

GCAGATGAAATGCTGCAAGTGTGAC





LAMC1
NM_002293
1437
GCCGTGATCT
1438
ACCTGCTTGC
1439
CCTCGGTACTTC
1440
GCCGTGATCTCAGACAGCTACTTTCCTCGGTACTTCATTGCTC





CAGACAGCTA

CCAAGAACT

ATTGCTCCTGCA

CTGCAAAGTTCTTGGGCAAGCAGGT





C











LAMC2
NM_005562
1441
ACTCAAGCGG
1442
ACTCCCTGAA
1443
AGGTCTTATCAG
1444
ACTCAAGCGGAAATTGAAGCAGATAGGTCTTATCAGCACAGTC





AAATTGAAGC

GCCGAGACAC

CACAGTCTCCGC

TCCGCCTCCTGGATTCAGTGTCTCGGCTTCAGGGAGT





A

T

CTCC







LAPTM5
NM_006762
1445
TGCTGGACTT
1446
TGAGATAGGT
1447
TCCTGACCCTCT
1448
TGCTGGACTTCTGCCTGAGCATCCTGACCCTCTGCAGCTCCTA





CTGCCTGAG

GGGCACTTCC

GCAGCTCCTACA

CATGGAAGTGCCCACCTATCTCA





LGALS3
NM_002306
1449
AGCGGAAAAT
1450
CTTGAGGGTT
1451
ACCCAGATAACG
1452
AGCGGAAAATGGCAGACAATTTTTCGCTCCATGATGCGTTATC





GGCAGACAAT

TGGGTTTCCA

CATCATGGAGCG

TGGGTCTGGAAACCCAAACCCTCAAG









A







LIG3
NM_002311
1453
GGAGGTGGAG
1454
ACAGGTGTCA
1455
CTGGACGCTCAG
1456
GGAGGTGGAGAAGGAGCCGGGCCAGAGACGAGCTCTGAGCG





AAGGAGCC

TCAGCGAGG

AGCTCGTCTCTG

TCCAGGCCTCGCTGATGACACCTGT





LIMS1
NM_004987
1457
TGAACAGTAA
1458
TTCTGGGAAC
1459
ACTGAGCGCACA
1460
TGAACAGTAATGGGGAGCTGTACCATGAGCAGTGTTTCGTGTG





TGGGGAGCTG

TGCTGGAAG

CGAAACACTGCT

CGCTCAGTGCTTCCAGCAGTTCCCAGAA





LOX
NM_002317
1461
CCAATGGGAG
1462
CGCTGAGGCT
1463
CAGGCTCAGCAA
1464
CCAATGGGAGAACAACGGGCAGGTGTTCAGCTTGCTGAGCCT





AACAACGG

GGTACTGTG

GCTGAACACCTG

GGGCTCACAGTACCAGCCTCAGCG





LRP1
NM_002332
1465
TTTGGCCCAA
1466
GTCTCGATGC
1467
TCCCGGCTGGGC
1468
TTTGGCCCAATGGGCTAAGCCTGGACATCCCGGCTGGGCGCC





TGGGCTAAG

GGTCGTAGAA

GCCTCTACT

TCTACTGGGTGGATGCCTTCTACGACCGCATCGAGAC







G









LTBP2
NM_000428
1469
GCACACCCAT
1470
GATGGCTGGC
1471
CTTTGCAGCCCT
1472
GCACACCCATCCTTGAGTCTCCTTTGCAGCCCTCAGAACTCCA





CCTTGAGTCT

CACGTAGT

CAGAACTCCAGC

GCCCCACTACGTGGCCAGCCATC





LUM
NM_002345
1473
GGCTCTTTTG
1474
AAAAGCAGCT
1475
CCTGACCTTCAT
1476
GGCTCTTTTGAAGGATTGGTAAACCTGACCTTCATCCATCTCC





AAGGATTGGT

GAAACAGCAT

CCATCTCCAGCA

AGCACAATCGGCTGAAAGAGGATGCTGTTTCAGCTGCTTTT





AA

C









MAGEA4
NM_002362
1477
GCATCTAACA
1478
CAGAGTGAAG
1479
CAGCTTCCCTTG
1480
GCATCTAACAGCCCTGTGCAGCAGCTTCCCTTGCCTCGTGTAA





GCCCTGTGC

AATGGGCCTC

CCTCGTGTAACA

CATGAGGCCCATTCTTCACTCTG





MANF
NM_006010
1481
CAGATGTGAA
1482
AAGGGAATCC
1483
TTCCTGATGATG
1484
CAGATGTGAAGCCTGGAGCTTTCCTGATGATGCTGGCCCTACA





GCCTGGAGC

CCTCATGG

CTGGCCCTACAG

GTACCCCCATGAGGGGATTCCCTT





MAOA
NM_000240
1485
GTGTCAGCCA
1486
CGACTACGTC
1487
CCGCGATACTCG
1488
GTGTCAGCCAAAGCATGGAGAATCAAGAGAAGGCGAGTATCG





AAGCATGGA

GAACATGTGG

CCTTCTCTTGAT

CGGGCCACATGTTCGACGTAGTCG





MAP3K5
NM_005923
1489
AGGACCAAGA
1490
CCTGTGGCCA
1491
CAGCCCAGAGAC
1492
AGGACCAAGAGGCTACGGAAAAGCAGCAGACATCTGGTCTCT





GGCTACGGA

TTTCAATGAT

CAGATGTCTGCT

GGGCTGTACAATCATTGAAATGGCCACAGG





MAP3K7
NM_145333
1493
CAGGCAAGAA
1494
CCTGTACCAG
1495
TGCTGGTCCTTT
1496
CAGGCAAGAACTAGTTGCAGAACTGGACCAGGATGAAAAGGA





CTAGTTGCAG

GCGAGATGTA

TCATCCTGGTCC

CCAGCAAAATACATCTCGCCTGGTACAGG





AA

T









MAP4K4
NM_004834
1497
TCGCCGAGAT
1498
CTGTTGTCTC
1499
AACGTTCCTTGT
1500
TCGCCGAGATTTCCTGAGACTGCAGCAGGAGAACAAGGAACG





TTCCTGAG

CGAAGAGCCT

TCTCCTGCTGCA

TTCCGAGGCTCTTCGGAGACAACAG





MAP7
NM_003980
1501
GAGGAACAGA
1502
CTGCCAACTG
1503
CATGTACAACAA
1504
GAGGAACAGAGGTGTCTGCACTTCCATGTACAACAAACGCTCC





GGTGTCTGCA

GCTTTCCA

ACGCTCCGGGAA

GGGAAATGGAAAGCCAGTTGGCAG





C











MAPKAPK3
NM_004635
1505
AAGCTGCAGA
1506
GTGGGCAATG
1507
ATTGGCACTGCC
1508
AAGCTGCAGAGATAATGCGGGATATTGGCACTGCCATCCAGTT





GATAATGCGG

TTATGGCTG

ATCCAGTTTCTG

TCTGCACAGCCATAACATTGCCCAC





MCM2
NM_004526
1509
GACTTTTGCC
1510
GCCACTAACT
1511
ACAGCTCATTGT
1512
GACTTTTGCCCGCTACCTTTCATTCCGGCGTGACAACAATGAG





CGCTACCTTT

GCTTCAGTAT

TGTCACGCCGGA

CTGTTGCTCTTCATACTGAAGCAGTTAGTGGC





C

GAAGAG









MCM3
NM_002388
1513
GGAGAACAAT
1514
ATCTCCTGGA
1515
TGGCCTTTCTGT
1516
GGAGAACAATCCCCTTGAGACAGAATATGGCCTTTCTGTCTAC





CCCCTTGAGA

TGGTGATGGT

CTACAAGGATCA

AAGGATCACCAGACCATCACCATCCAGGAGAT









CCA







MCM6
NM_005915
1517
TGATGGTCCT
1518
TGGGACAGGA
1519
CAGGTTTCATAC
1520
TGATGGTCCTATGTGTCACATTCATCACAGGTTTCATACCAAC





ATGTGTCACA

AACACACCAA

CAACACAGGCTT

ACAGGCTTCAGCACTTCCTTTGGTGTGTTTCCTGTCCCA





TTCA



CAGCAC







MDK
NM_002391
1521
GGAGCCGACT
1522
GACTTTGGTG
1523
ATCACACGCACC
1524
GGAGCCGACTGCAAGTACAAGTTTGAGAACTGGGGTGCGTGT





GCAAGTACA

CCTGTGCC

CCAGTTCTCAAA

GATGGGGGCACAGGCACCAAAGTC





MDM2
NM_002392
1525
CTACAGGGAC
1526
ATCCAACCAA
1527
CTTACACCAGCA
1528
CTACAGGGACGCCATCGAATCCGGATCTTGATGCTGGTGTAAG





GCCATCGAA

TCACCTGAAT

TCAAGATCCGG

TGAACATTCAGGTGATTGGTTGGAT







GTT









MELK
NM_014791
1529
AGGATCGCCT
1530
TGCACATAAG
1531
CCCGGGTTGTCT
1532
AGGATCGCCTGTCAGAAGAGGAGACCCGGGTTGTCTTCCGTC





GTCAGAAGAG

CAACAGCAGA

TCCGTCAGATAG

AGATAGTATCTGCTGTTGCTTATGTGCA





MET
NM_000245
1533
GACATTTCCA
1534
CTCCGATCGC
1535
TGCCTCTCTGCC
1536
GACATTTCCAGTCCTGCAGTCAATGCCTCTCTGCCCCACCCTT





GTCCTGCAGT

ACACATTTGT

CCACCCTTTGT

TGTTCAGTGTGGCTGGTGCCACGACAAATGTGTGCGATCGGA





CA





G





MGMT
NM_002412
1537
GTGAAATGAA
1538
GACCCTGCTC
1539
CAGCCCTTTGGG
1540
GTGAAATGAAACGCACCACACTGGACAGCCCTTTGGGGAAGC





ACGCACCACA

ACAACCAGAC

GAAGCTGG

TGGAGCTGTCTGGTTGTGAGCAGGGTC





MGST1
NM_020300
1541
ACGGATCTAC
1542
TCCATATCCA
1543
TTTGACACCCCT
1544
ACGGATCTACCACACCATTGCATATTTGACACCCCTTCCCCAG





CACACCATTG

ACAAAAAAAC

TCCCCAGCCA

CCAAATAGAGCTTTGAGTTTTTTTGTTGGATATGGA





C

TCAAAG









MICA
NM_000247
1545
ATGGTGAATG
1546
AAGCCAGAAG
1547
CGAGGCCTCAGA
1548
ATGGTGAATGTCACCCGCAGCGAGGCCTCAGAGGGCAACATT





TCACCCGC

CCCTGCAT

GGGCAACATTAC

ACCGTGACATGCAGGGCTTCTGGCTT





MKI67
NM_002417
1549
GATTGCACCA
1550
TCCAAAGTGC
1551
CCACTCTTCCTT
1552
GATTGCACCAGGGCAGAACAGGGGAGGGTGTTCAAGGAAGAG





GGGCAGAA

CTCTGCTAAG

GAACACCCTCCC

TGGCTCTTAGCAGAGGCACTTTGGA







A









MLXIP
NM_014938
1553
TGCTTAGCTG
1554
CAGCCTACTC
1555
CATGAGATGCCA
1556
TGCTTAGCTGGCATGTGGCCGCATGAGATGCCAGGAGACCCT





GCATGTGG

TCCATGGGC

GGAGACCCTTCC

TCCCTGCCCATGGAGAGTAGGCTG





MMP11
NM_005940
1557
CCTGGAGGCT
1558
TACAATGGCT
1559
ATCCTCCTGAAG
1560
CCTGGAGGCTGCAACATACCTCAATCCTGTCCCAGGCCGGAT





GCAACATACC

TTGGAGGATA

CCCTTTTCGCAG

CCTCCTGAAGCCCTTTTCGCAGCACTGCTATCCTCCAAAGCCA







GCA

C

TTGTA





MMP2
NM_004530
1561
CAGCCAGAAG
1562
AGACACCATC
1563
AAGTCCGAATCT
1564
CAGCCAGAAGCGGAAACTTAAAAAGTCCGAATCTCTGCTCCCT





CGGAAACTTA

ACCTGTGCC

CTGCTCCCTGCA

GCAGGGCACAGGTGATGGTGTCT





MMP7
NM_002423
1565
GGATGGTAGC
1566
GGAATGTCCC
1567
CCTGTATGCTGC
1568
GGATGGTAGCAGTCTAGGGATTAACTTCCTGTATGCTGCAACT





AGTCTAGGGA

ATACCCAAAG

AACTCATGAACT

CATGAACTTGGCCATTCTTTGGGTATGGGACATTCC





TTAACT

AA

TGGC







MMP9
NM_004994
1569
GAGAACCAAT
1570
CACCCGAGTG
1571
ACAGGTATTCCT
1572
GAGAACCAATCTCACCGACAGGCAGCTGGCAGAGGAATACCT





CTCACCGACA

TAACCATAGC

CTGCCAGCTGCC

GTACCGCTATGGTTACACTCGGGTG





MPPED2
NM_001584
1573
CCGACCAACC
1574
AGGGCATTTA
1575
ATTTGACCTTCC
1576
CCGACCAACCCTCCAATTATATTTGACCTTCCAAACCCACAGG





CTCCAATTA

GAGCTTCAGG

AAACCCACAGGG

GTTCCTGAAGCTCTAAATGCCCT







A









MRC1
NM_002438
1577
CTTGACCTCA
1578
GGACTGCGGT
1579
CCAACCGCTGTT
1580
CTTGACCTCAGGACTCTGGATTGGACTTAACAGTCTGAGCTTC





GGACTCTGGA

CACTCCAC

GAAGCTCAGACT

AACAGCGGTTGGCAGTGGAGTGACCGCAGTCC





TT











MRPL13
NM_014078
1581
TCCGGTTCCC
1582
GTGGAAAAAC
1583
CGGCTGGAAATT
1584
TCCGGTTCCCTTCGTTTAGGTCGGCTGGAAATTATGTCCTCCG





TTCGTTTAG

TGCGGAAAAC

ATGTCCTCCGTC

TCGGTTTTCCGCAGTTTTTCCAC





MSH2
NM_000251
1585
GATGCAGAAT
1586
TCTTGGCAAG
1587
CAAGAAGATTTA
1588
GATGCAGAATTGAGGCAGACTTTACAAGAAGATTTACTTCGTC





TGAGGCAGAC

TCGGTTAAGA

CTTCGTCGATTC

GATTCCCAGATCTTAACCGACTTGCCAAGA









CCAGA







MSH3
NM_002439
1589
TGATTACCAT
1590
CTTGTGAAAA
1591
TCCCAATTGTCG
1592
TGATTACCATCATGGCTCAGATTGGCTCCTATGTTCCTGCAGA





CATGGCTCAG

TGCCATCCAC

CTTCTTCTGCAG

AGAAGCGACAATTGGGATTGTGGATGGCATTTTCACAAG





A











MSH6
NM_000179
1593
TCTATTGGGG
1594
CAAATTGCGA
1595
CCGTTACCAGCT
1596
TCTATTGGGGGATTGGTAGGAACCGTTACCAGCTGGAAATTCC





GATTGGTAGG

GTGGTGAAAT

GGAAATTCCTGA

TGAGAATTTCACCACTCGCAATTTG









GA







MTA1
NM_004689
1597
CCGCCCTCAC
1598
GGAATAAGTT
1599
CCCAGTGTCCGC
1600
CCGCCCTCACCTGCAGAGAAACGCGCTCCTTGGCGGACACTG





CTGAAGAGA

AGCCGCGCTT

CAAGGAGCG

GGGGAGGAGAGGAAGAAGCGCGGCTAACTTATTCC







CT









MTPN
NM_145808
1601
GGTGGAAGGA
1602
CAGCAGCAGA
1603
AAGCTGCCCACA
1604
GGTGGAAGGAAACCTCTTCATTATGCAGCAGATTGTGGGCAGC





AACCTCTTCA

AATTCCAGG

ATCTGCTGCATA

TTGAAATCCTGGAATTTCTGCTGCTG





MTSS1
NM_014751
1605
TTCGACAAGT
1606
CTTGGAACAT
1607
CCAAGAAACAGC
1608
TTCGACAAGTCCTCCACCATTCCAAGAAACAGCGACATCAGCC





CCTCCACCAT

CCGTCGGTAG

GACATCAGCCAG

AGTCCTACCGACGGATGTTCCAAG





MUC1
NM_002456
1609
GGCCAGGATC
1610
CTCCACGTCG
1611
CTCTGGCCTTCC
1612
GGCCAGGATCTGTGGTGGTACAATTGACTCTGGCCTTCCGAG





TGTGGTGGTA

TGGACATTGA

GAGAAGGTACC

AAGGTACCATCAATGTCCACGACGTGGAG





MVP
NM_017458
1613
ACGAGAACGA
1614
GCATGTAGGT
1615
CGCACCTTTCCG
1616
ACGAGAACGAGGGCATCTATGTGCAGGATGTCAAGACCGGAA





GGGCATCTAT

GCTTCCAATC

GTCTTGACATCC

AGGTGCGCGCTGTGATTGGAAGCACCTACATGC





GT

AC

T







MYBL2
NM_002466
1617
GCCGAGATCG
1618
CTTTTGATGG
1619
CAGCATTGTCTG
1620
GCCGAGATCGCCAAGATGTTGCCAGGGAGGACAGACAATGCT





CCAAGATG

TAGAGTTCCA

TCCTCCCTGGCA

GTGAAGAATCACTGGAACTCTACCATCAAAAG







GTGATTC









MYBPC1
NM_002465
1621
CAGCAACCAG
1622
CAGCAGTAAG
1623
AAATTCGCAAGC
1624
CAGCAACCAGGGAGTCTGTACCCTGGAAATTCGCAAGCCCAG





GGAGTCTGTA

TGCCTCCATC

CCAGCCCCTAT

CCCCTATGATGGAGGCACTTACTGCTG





MYC
NM_002467
1625
TCCCTCCACT
1626
CGGTTGTTGC
1627
TCTGACACTGTC
1628
TCCCTCCACTCGGAAGGACTATCCTGCTGCCAAGAGGGTCAA





CGGAAGGACT

TGATCTGTCT

CAACTTGACCCT

GTTGGACAGTGTCAGAGTCCTGAGACAGATCAGCAACAACCG





A

CA

CTT







MYLK3
NM_182493
1629
CACCTGACTG
1630
GATGTAGTGC
1631
CACACCCTCACA
1632
CACCTGACTGAGCTGGATGTGGTCCTGTTCACCAGGCAGATCT





AGCTGGATGT

TGGTGCAGGT

GATCTGCCTGGT

GTGAGGGTGTGCATTACCTGCACCAGCACTACATC





MYO6
NM_004999
1633
AAGCAGTTCT
1634
GATGAGCTCG
1635
CAATCCTCAGGG
1636
AAGCAGTTCTGGAGCAGGAGCGCAGGGACCGGGAGCTGGCC





GGAGCAGGAG

GCTTCACTCT

CCAGCTCCC

CTGAGGATTGCCCAGAGTGAAGCCGAGCTCATC





NCAM1
NM_000615
1637
TAGTTCCCAG
1638
CAGCCTTGTT
1639
CTCAGCCTCGTC
1640
TAGTTCCCAGCTGACCATCAAAAAGGTGGATAAGAACGACGAG





CTGACCATCA

CTCAGCAATG

GTTCTTATCCAC

GCTGAGTACATCTGCATTGCTGAGAACAAGGCTG









C







NCAPD3
NM_015261
1641
TCGTTGCTTA
1642
CTCCAGACAG
1643
CTACTGTCCGCA
1644
TCGTTGCTTAGACAAGGCGCCTACTGTCCGCAGCAAGGCACT





GACAAGGCG

TGTGCAAAGC

GCAAGGCACTGT

GTCCAGCTTTGCACACTGTCTGGAG





NCOR1
NM_006311
1645
AACCGTTACA
1646
TCTGGAGAGA
1647
CCAGGCTCAGTC
1648
AACCGTTACAGCCCAGAATCCCAGGCTCAGTCTGTCCATCATC





GCCCAGAATC

CCCTTGAACC

TGTCCATCATCA

AAAGACCAGGTTCAAGGGTCTCTCCAGA





NCOR2
NM_006312
1649
CGTCATCTAC
1650
GAGCACTGGG
1651
CCTCATAGGACA
1652
CGTCATCTACGAAGGCAAGAAGGGCCACGTCTTGTCCTATGA





GAAGGCAAGA

TCACAGACAT

AGACGTGGCCCT

GGGTGGCATGTCTGTGACCCAGTGCTC





NDRG1
NM_006096
1653
AGGGCAACAT
1654
CAGTGCTCCT
1655
CTGCAAGGACAC
1656
AGGGCAACATTCCACAGCTGCCCTGGCTGTGATGAGTGTCCTT





TCCACAGC

ACTCCGGC

TCATCACAGCCA

GCAGGGGCCGGAGTAGGAGCACTG





NDUFS5
NM_004552
1657
AGAAGAGTCA
1658
AGGCCGAACC
1659
TGTCCAAGAAAG
1660
AGAAGAGTCAAGGGCACGAGCATCGGGTAGCCATGCCTTTCT





AGGGCACGAG

TTTTCTGG

GCATGGCTACCC

TGGACATCCAGAAAAGGTTCGGCCT





NEK2
NM_002497
1661
GTGAGGCAGC
1662
TGCCAATGGT
1663
TGCCTTCCCGGG
1664
GTGAGGCAGCGCGACTCTGGCGACTGGCCGGCCATGCCTTCC





GCGACTCT

GTACAACACT

CTGAGGACT

CGGGCTGAGGACTATGAAGTGTTGTACACCATTGGCA







TCA









NETO2
NM_018092
1665
CCAGGGCACC
1666
AACGGTAAAT
1667
AGCCAACCCTTT
1668
CCAGGGCACCATACTGTTTCCAGCAGCCAACCCTTTTCTCCCA





ATACTGTTTC

CAAGGTCTTC

TCTCCCATCACA

TCACAACTACGAAGACCTTGATTTACCGTT







GT









NEXN
NM_144573
1669
AGGAGGAGGA
1670
GAGCTCCTGA
1671
TCATCTTCAGCA
1672
AGGAGGAGGAAGAAGGTAGCATCATGAATGGCTCCACTGCTG





AGAAGGTAGC

TCTGGTTTGC

GTGGAGCCATTC

AAGATGAAGAGCAAACCAGATCAGGAGCTC





A



A







NFAT5
NM_006599
1673
CTGAACCCCT
1674
AGGAAACGAT
1675
CGAGAATCAGTC
1676
CTGAACCCCTCTCCTGGTCACCGAGAATCAGTCCCCGTGGAG





CTCCTGGTC

GGCGAGGT

CCCGTGGAGTTC

TTCCCCCTCCACCTCGCCATCGTTTCCT





NFATC2
NM_173091
1677
CAGTCAAGGT
1678
CTTTGGCTCG
1679
CGGGTTCCTACC
1680
CAGTCAAGGTCAGAGGCTGAGCCCGGGTTCCTACCCCACAGT





CAGAGGCTGA

TGGCATTC

CCACAGTCATTC

CATTCAGCAGCAGAATGCCACGAGCCAAAG





G











NFKB1
NM_003998
1681
CAGACCAAGG
1682
AGCTGCCAGT
1683
AAGCTGTAAACA
1684
CAGACCAAGGAGATGGACCTCAGCGTGGTGCGGCTCATGTTT





AGATGGACCT

GCTATCCG

TGAGCCGCACCA

ACAGCTTTTCTTCCGGATAGCACTGGCAGCT





NFKBIA
NM_020529
1685
CTACTGGACG
1686
CCTTGACCAT
1687
CTCGTCTTTCAT
1688
CTACTGGACGACCGCCACGACAGCGGCCTGGACTCCATGAAA





ACCGCCAC

CTGCTCGTAC

GGAGTCCAGGCC

GACGAGGAGTACGAGCAGATGGTCAAGG







T









NME1
NM_000269
1689
CCAACCCTGC
1690
ATGTATAATG
1691
CCTGGGACCATC
1692
CCAACCCTGCAGACTCCAAGCCTGGGACCATCCGTGGAGACT





AGACTCCAA

TTCCTGCCAA

CGTGGAGACTTC

TCTGCATACAAGTTGGCAGGAACATTATACAT







CTTGTATG

T







NNMT
NM_006169
1693
CCTAGGGCAG
1694
CTAGTCCAGC
1695
CCCTCTCCTCAT
1696
CCTAGGGCAGGGATGGAGAGAGAGTCTGGGCATGAGGAGAG





GGATGGAG

CAAACATCCC

GCCCAGACTCTC

GGTCTCGGGATGTTTGGCTGGACTAG





NOS3
NM_000603
1697
ATCTCCGCCT
1698
TCGGAGCCAT
1699
TTCACTCGCTTC
1700
ATCTCCGCCTCGCTCATGGGCACGGTGATGGCGAAGCGAGTG





CGCTCATG

ACAGGATTGT

GCCATCACCG

AAGGCGACAATCCTGTATGGCTCCGA







C









NOX4
NM_016931
1701
CCTCAACTGC
1702
TGCTTGGAAC
1703
CCGAACACTCTT
1704
CCTCAACTGCAGCCTTATCCTTTTACCCATGTGCCGAACACTC





AGCCTTATCC

CTTCTGTGAT

GGCTTACCTCCG

TTGGCTTACCTCCGAGGATCACAGAAGGTTCCAAGCA





NPBWR1
NM_005285
1705
TCACCAACCT
1706
GATGTTGATG
1707
ATCGCCGACGAG
1708
TCACCAACCTGTTCATCCTCAACCTGGCCATCGCCGACGAGCT





GTTCATCCTC

GGCAGCAC

CTCTTCACG

CTTCACGCTGGTGCTGCCCATCAACATC





NPM1
NM_002520
1709
AATGTTGTCC
1710
CAAGCAAAGG
1711
AACAGGCATTTT
1712
AATGTTGTCCAGGTTCTATTGCCAAGAATGTGTTGTCCAAAAT





AGGTTCTATT

GTGGAGTTC

GGACAACACATT

GCCTGTTTAGTTTTTAAAGATGGAACTCCACCCTTTGCTTG





GC



CTTG







NRG1
NM_013957
1713
CGAGACTCTC
1714
CTTGGCGTGT
1715
ATGACCACCCCG
1716
CGAGACTCTCCTCATAGTGAAAGGTATGTGTCAGCCATGACCA





CTCATAGTGA

GGAAATCTAC

GCTCGTATGTCA

CCCCGGCTCGTATGTCACCTGTAGATTTCCACACGCCAAG





AAGGTAT

AG









NRIP3
NM_020645
1717
CCCACAAGCA
1718
TGCTCAATCT
1719
AGCTTTCTCTAC
1720
CCCACAAGCATGAAGGAGAAAAGCTTTCTCTACCCCGGCATCT





TGAAGGAGA

GGCCCACTA

CCCGGCATCTCA

CAAAGTAGTGGGCCAGATTGAGCA





NRP1
NM_003873
1721
CAGCTCTCTC
1722
CCCAGCAGCT
1723
CAGGATCTACCC
1724
CAGCTCTCTCCACGCGATTCATCAGGATCTACCCCGAGAGAG





CACGCGATTC

CCATTCTGA

CGAGAGAGCCAC

CCACTCATGGCGGACTGGGGCTCAGAATGGAGCTGCTGGG









TCAT







NUP62
NM_153719
1725
AGCCTCTTTG
1726
CTGTGGTCAC
1727
TCATCTGCCACC
1728
AGCCTCTTTGCGTCAATAGCAACTGCTCCAACCTCATCTGCCA





CGTCAATAGC

AGGGGTACAG

ACTGGACTCTCC

CCACTGGACTCTCCCTCTGTACCCCTGTGACCACAG





OAZ1
NM_004152
1729
AGCAAGGACA
1730
GAAGACATGG
1731
CTGCTCCTCAGC
1732
AGCAAGGACAGCTTTGCAGTTCTCCTGGAGTTCGCTGAGGAG





GCTTTGCAGT

TCGGCTCG

GAACTCCAGGAG

CAGCTGCGAGCCGACCATGTCTTC





OCLN
NM_002538
1733
CCCTCCCATC
1734
GACGCGGGAG
1735
CTCCTCCCTCGG
1736
CCCTCCCATCCGAGTTTCAGGTGAATTGGTCACCGAGGGAGG





CGAGTTTC

TGTAGGTG

TGACCAATTCAC

AGGCCGACACACCACACCTACACTCCCGCGTC





ODC1
NM_002539
1737
AGAGATCACC
1738
CGGGCTCAGC
1739
CCAGCGTTGGAC
1740
AGAGATCACCGGCGTAATCAACCCAGCGTTGGACAAATACTTT





GGCGTAATCA

TATGATTCTC

AAATACTTTCCG

CCGTCAGACTCTGGAGTGAGAATCATAGCTGAGCCCG





A

A

TCA







OLFML2B
NM_015441
1741
CATGTTGGAA
1742
CACCAGTTTG
1743
TGGCCTGGATCT
1744
CATGTTGGAAGGAGCGTTCTATGGCCTGGATCTCCTGAAGCTA





GGAGCGTTCT

GTGGTGACTG

CCTGAAGCTACA

CATTCAGTCACCACCAAACTGGTG





OLFML3
NM_020190
1745
TCAGAACTGA
1746
CCAGATAGTC
1747
CAGACGATCCAC
1748
TCAGAACTGAGGCCGACACCATCTCCGGGAGAGTGGATCGTC





GGCCGACAC

TACCTCCCGC

TCTCCCGGAGAT

TGGAGCGGGAGGTAGACTATCTGG







T









OMD
NM_005014
1749
CGCAAACTCA
1750
CAGTCACAGC
1751
TCCGATGCACAT
1752
CGCAAACTCAAGACTATCCCAAATATTCCGATGCACATTCAGC





AGACTATCCC

CTCAATTTCA

TCAGCAACTCTA

AACTCTACCTTCAGTTCAATGAAATTGAGGCTGTGACTG





A

TT

CC







OR51E1
NM_152430
1753
GCATGCTTTC
1754
AGAAGATGGC
1755
TCCTCATCTCCA
1756
GCATGCTTTCAGGCATTGACATCCTCATCTCCACCTCATCCAT





AGGCATTGA

CAGCATTTTG

CCTCATCCATGC

GCCCAAAATGCTGGCCATCTTCT





OR51E2
NM_030774
1757
TATGGTGCCA
1758
GTCCTTGTCA
1759
ACATAGCCAGCA
1760
TATGGTGCCAAAACCAAACAGATCAGAACACGGGTGCTGGCT





AAACCAAACA

CAGCTGATCT

CCCGTGTTCTGA

ATGTTCAAGATCAGCTGTGACAAGGAC







TG









OSM
NM_020530
1761
GTTTCTGAAG
1762
AGGTGTCTGG
1763
CTGAGCTGGCCT
1764
GTTTCTGAAGGGGAGGTCACAGCCTGAGCTGGCCTCCTATGC





GGGAGGTCAC

TTTGGGACA

CCTATGCCTCAT

CTCATCATGTCCCAAACCAGACACCT





PAGE1
NM_003785
1765
CAACCTGACG
1766
CAGATGCTCC
1767
CCAACTCAAAGT
1768
CAACCTGACGAAGTGGAATCACCAACTCAAAGTCAGGATTCTA





AAGTGGAATC

CTCATCCTCT

CAGGATTCTACA

CACCTGCTGAAGAGAGAGAGGATGAGGGAGCATCTG









CCTGC







PAGE4
NM_007003
1769
GAATCTCAGC
1770
GTTCTTCGAT
1771
CCAACTGACAAT
1772
GAATCTCAGCAAGAGGAACCACCAACTGACAATCAGGATATTG





AAGAGGAACC

CGGAGGTGTT

CAGGATATTGAA

AACCTGGACAAGAGAGAGAAGGAACACCTCCGATCGAAGAAC





A



CCTGG







PAK6
NM_020168
1773
CCTCCAGGTC
1774
GTCCCTTCAG
1775
AGTTTCAGGAAG
1776
CCTCCAGGTCACCCACAGCCAGTTTCAGGAAGGCTGCCCCTC





ACCCACAG

GCCAGAACTT

GCTGCCCCTCTC

TCTCCCACTAAGTTCTGGCCTGAAGGGAC





PATE1
NM_138294
1777
TGGTAATCCC
1778
TCCACCTTAT
1779
CAGCACAGTTCT
1780
TGGTAATCCCTGGTTAACCTTCATGGGCTGCCTAAAGAACTGT





TGGTTAACCT

GCCTTTCACA

TTAGGCAGCCCA

GCTGATGTGAAAGGCATAAGGTGGA





TC











PCA3
NR_015342
1781
CGTGATTGTC
1782
AGAAAGGGGA
1783
CTGAGATGCTCC
1784
CGTGATTGTCAGGAGCAAGACCTGAGATGCTCCCTGCCTTCAG





AGGAGCAAGA

GATGCAGAGG

CTGCCTTCAGTG

TGTCCTCTGCATCTCCCCTTTCT





PCDHGB7
NM_018927
1785
CCCAGCGTTG
1786
GAAACGCCAG
1787
ATTCTTAAACAG
1788
CCCAGCGTTGAAGCAGATAAGAAGATTCTTAAACAGCAAGCCC





AAGCAGAT

TCCGTGTT

CAAGCCCCGCC

CGCCCAACACGGACTGGCGTTTC





PCNA
NM_002592
1789
GAAGGTGTTG
1790
GGTTTACACC
1791
ATCCCAGCAGGC
1792
GAAGGTGTTGGAGGCACTCAAGGACCTCATCAACGAGGCCTG





GAGGCACTCA

GCTGGAGCTA

CTCGTTGATGAG

CTGGGATATTAGCTCCAGCGGTGTAAACC





AG

A









PDE9A
NM_
1793
TTCCACAACT
1794
AGACTGCAGA
1795
TACATCATCTGG
1796
TTCCACAACTTCCGGCACTGCTTCTGCGTGGCCCAGATGATGT



001001570

TCCGGCAC

GCCAGACCA

GCCACGCAGAAG

ACAGCATGGTCTGGCTCTGCAGTCT





PDGFRB
NM_002609
1797
CCAGCTCTCC
1798
GGGTGGCTCT
1799
ATCAATGTCCCT
1800
CCAGCTCTCCTTCCAGCTACAGATCAATGTCCCTGTCCGAGTG





TTCCAGCTAC

CACTTAGCTC

GTCCGAGTGCTG

CTGGAGCTAAGTGAGAGCCACCC





PECAM1
NM_000442
1801
TGTATTTCAA
1802
TTAGCCTGAG
1803
TTTATGAACCTG
1804
TGTATTTCAAGACCTCTGTGCACTTATTTATGAACCTGCCCTG





GACCTCTGTG

GAATTGCTGT

CCCTGCTCCCAC

CTCCCACAGAACACAGCAATTCCTCAGGCTAA





CACTT

GTT

A







PEX10
NM_153818
1805
GGAGAAGTTC
1806
ATCTGTGTCC
1807
CTACCTTCGGCA
1808
GGAGAAGTTCCCTCCCCAGAAGCTCATCTACCTTCGGCACTAC





CCTCCCCAG

AGGCCCAC

CTACCGCTGAGC

CGCTGAGCCGGCGCCCGGGTGGGCCTGGACACAGAT





PGD
NM_002631
1809
ATTCCCATGC
1810
CTGGCTGGAA
1811
ACTGCCCTCTCC
1812
ATTCCCATGCCCTGTTTTACCACTGCCCTCTCCTTCTATGACG





CCTGTTTTAC

GCATCTCAT

TTCTATGACGGG

GGTACAGACATGAGATGCTTCCAGCCAG









T







PGF
NM_002632
1813
GTGGTTTTCC
1814
AGCAAGGGAA
1815
ATCTTCTCAGAC
1816
GTGGTTTTCCCTCGGAGCCCCCTGGCTCGGGACGTCTGAGAA





CTCGGAGC

CAGCCTCAT

GTCCCGAGCCAG

GATGCCGGTCATGAGGCTGTTCCCTTGCT





PGK1
NM_000291
1817
AGAGCCAGTT
1818
CTGGGCCTAC
1819
TCTCTGCTGGGC
1820
AGAGCCAGTTGCTGTAGAACTCAAATCTCTGCTGGGCAAGGAT





GCTGTAGAAC

ACAGTCCTTC

AAGGATGTTCTG

GTTCTGTTCTTGAAGGACTGTGTAGGCCCAG





TCAA

A

TTC







PGR
NM_000926
1821
GATAAAGGAG
1822
TCACAAGTCC
1823
TAAATTGCCGTC
1824
GATAAAGGAGCCGCGTGTCACTAAATTGCCGTCGCAGCCGCA





CCGCGTGTCA

GGCACTTGAG

GCAGCCGCA

GCCACTCAAGTGCCGGACTTGTGA





PHTF2
NM_020432
1825
GATATGGCTG
1826
GGTTTGGGTG
1827
ACAATCTGGCAA
1828
GATATGGCTGATGCTGCTCCTGGGAACTGTGCATTGCCAGATT





ATGCTGCTCC

TTCTTGTGGA

TGCACAGTTCCC

GTTTCCACAAGAACACCCAAACC





PIK3C2A
NM_002645
1829
ATACCAATCA
1830
CACACTAGCA
1831
TGTGCTGTGACT
1832
ATACCAATCACCGCACAAACCCAGGCTATTTGTTAAGTCCAGT





CCGCACAAAC

TTTTCTCCGC

GGACTTAACAAA

CACAGCACAAAGAAACATATGCGGAGAAAATGCTAGTGTG





C

ATA

TAGCCT







PIK3CA
NM_006218
1833
GTGATTGAAG
1834
GTCCTGCGTG
1835
TCCTGCTTCTCG
1836
GTGATTGAAGAGCATGCCAATTGGTCTGTATCCCGAGAAGCAG





AGCATGCCAA

GGAATAGC

GGATACAGACCA

GATTTAGCTATTCCCACGCAGGAC





PIK3CG
NM_002649
1837
GGAGAACTCA
1838
TGATGCTTAG
1839
TTCTGGACAATT
1840
GGAGAACTCAATGTCCATCTCCATTCTTCTGGACAATTACTGC





ATGTCCATCT

GCAGGGCT

ACTGCCACCCGA

CACCCGATAGCCCTGCCTAAGCATCA





CC











PIM1
NM_002648
1841
CTGCTCAAGG
1842
GGATCCACTC
1843
TACACTCGGGTC
1844
CTGCTCAAGGACACCGTCTACACGGACTTCGATGGGACCCGA





ACACCGTCTA

TGGAGGGC

CCATCGAAGTCC

GTGTATAGCCCTCCAGAGTGGATCC





PLA2G7
NM_005084
1845
CCTGGCTGTG
1846
TGACCCATGC
1847
TGGCAATACATA
1848
CCTGGCTGTGGTTTATCCTTTTGACTGGCAATACATAAATCCT





GTTTATCCTT

TGATGATTTC

AATCCTGTTGCC

GTTGCCCATATGAAATCATCAGCATGGGTCA









CA




PLAU
NM_002658
1849
GTGGATGTGC
1850
CTGCGGATCC
1851
AAGCCAGGCGTC
1852
GTGGATGTGCCCTGAAGGACAAGCCAGGCGTCTACACGAGAG





CCTGAAGGA

AGGGTAAGAA

TACACGAGAGTC

TCTCACACTTCTTACCCTGGATCCGCAG









TCAC




PLAUR
NM_002659
1853
CCCATGGATG
1854
CCGGTGGCTA
1855
CATTGACTGCCG
1856
CCCATGGATGCTCCTCTGAAGAGACTTTCCTCATTGACTGCCG





CTCCTCTGAA

CCAGACATTG

AGGCCCCATG

AGGCCCCATGAATCAATGTCTGGTAGCCACCGG





PLG
NM_000301
1857
GGCAAAATTT
1858
ATGTATCCAT
1859
TGCCAGGCCTGG
1860
GGCAAAATTTCCAAGACCATGTCTGGACTGGAATGCCAGGCCT





CCAAGACCAT

GAGCGTGTGG

GACTCTCA

GGGACTCTCAGAGCCCACACGCTCATGGATACAT





PLK1
NM_005030
1861
AATGAATACA
1862
TGTCTGAAGC
1863
AACCCCGTGGCC
1864
AATGAATACAGTATTCCCAAGCACATCAACCCCGTGGCCGCCT





GTATTCCCAA

ATCTTCTGGA

GCCTCC

CCCTCATCCAGAAGATGCTTCAGACA





GCACAT

TGA









PLOD2
NM_000935
1865
CAGGGAGGTG
1866
TCTCCCAGGA
1867
TCCAGCCTTTTC
1868
CAGGGAGGTGGTTGCAAATTTCTAAGGTACAATTGCTCTATTG





GTTGCAAAT

TGCATGAAG

GTGGTGACTCAA

AGTCACCACGAAAAGGCTGGAGCTTCATGCATCCTGGGAGA





PLP2
NM_002668
1869
CCTGATCTGC
1870
GCAGCAAGGA
1871
ACACCAGGCTAC
1872
CCTGATCTGCTTCAGTGCCTCCACACCAGGCTACTCCTCCCTG





TTCAGTGCC

TCATCTCAAT

TCCTCCCTGTCG

TCGGTGATTGAGATGATCCTTGCTGC







C









PNLIPRP2
NM_005396
1873
TGGAGAAGGT
1874
CACGGCTTGG
1875
ACCCGTGCCTCC
1876
TGGAGAAGGTGAACTGCATCTGTGTGGACTGGAGGCACGGGT





GAACTGCATC

GTGTACATT

AGTCCACAC

CCCGGGCAATGTACACCCAAGCCGTG





POSTN
NM_006475
1877
GTGGCCCAAT
1878
TCACAGGTGC
1879
TTCTCCATCTGG
1880
GTGGCCCAATTAGGCTTGGCATCTGCTCTGAGGCCAGATGGA





TAGGCTTG

CAGCAAAG

CCTCAGAGCAGA

GAATACACTTTGCTGGCACCTGTGA





PPAP2B
NM_003713
1881
ACAAGCACCA
1882
CACGAAGAAA
1883
ACCAGGGCTCCT
1884
ACAAGCACCATCCCAGTGATGTTCTGGCAGGATTTGCTCAAGG





TCCCAGTGA

ACTATGCAGC

TGAGCAAATCCT

AGCCCTGGTGGCCTGCTGCATAGTTTTCTTCGTG







AG









PPFIA3
NM_003660
1885
CCTGGAGCTC
1886
AGCCACATAG
1887
CACCCACTTTAC
1888
CCTGGAGCTCCGTTACTCTCAGGCACCCACTTTACCTTCTGGT





CGTTACTCTC

GGATCCAGG

CTTCTGGTGCCC

GCCCACCTGGATCCCTATGTGGCT





PPP1R12A
NM_002480
1889
CGGCAAGGGG
1890
TGCCTGGCAT
1891
CCGTTCTTCTTC
1892
CGGCAAGGGGTTGATATAGAAGCAGCTCGAAAGGAAGAAGAA





TTGATATAGA

CTCTAAGCA

CTTTCGAGCTGC

CGGATCATGCTTAGAGATGCCAGGCA





PPP3CA
NM_000944
1893
ATACTCCGAG
1894
GGAAGCCTGT
1895
TACATGCGGTAC
1896
ATACTCCGAGCCCACGAAGCCCAAGATGCAGGGTACCGCATG





CCCACGAA

TGTTTGGC

CCTGCATCTTGG

TACAGGAAAAGCCAAACAACAGGCTTCC





PRIMA1
NM_178013
1897
ATCCTCTTCC
1898
CCCAGCTGAG
1899
TGACGCATCCAG
1900
ATCCTCTTCCCTGAGCCGCTGACGCATCCAGGGCTCTAGTCTG





CTGAGCCG

AGGGAATTTA

GGCTCTAGTCTG

CACATAAATTCCCTCTCAGCTGGG





PRKAR1B
NM_002735
1901
ACAAAACCAT
1902
TGTCATCCAG
1903
AAGGCCATCTCC
1904
ACAAAACCATGACTGCGCTGGCCAAGGCCATCTCCAAGAACG





GACTGCGCT

GTGAGCGA

AAGAACGTGCTC

TGCTCTTCGCTCACCTGGATGACA





PRKAR2B
NM_002736
1905
TGATAATCGT
1906
GCACCAGGAG
1907
CGAACTGGCCTT
1908
TGATAATCGTGGGAGTTTCGGCGAACTGGCCTTAATGTACAAT





GGGAGTTTCG

AGGTAGCAGT

AATGTACAATAC

ACACCCAGAGCAGCTACAATCACTGCTACCTCTCCTGGTGC









ACCCA







PRKCA
NM_002737
1909
CAAGCAATGC
1910
GTAAATCCGC
1911
CAGCCTCTGCGG
1912
CAAGCAATGCGTCATCAATGTCCCCAGCCTCTGCGGAATGGAT





GTCATCAATG

CCCCTCTTCT

AATGGATCACAC

CACACTGAGAAGAGGGGGCGGATTTAC





T



T







PRKCB
NM_002738
1913
GACCCAGCTC
1914
CCCATTCACG
1915
CCAGACCATGGA
1916
GACCCAGCTCCACTCCTGCTTCCAGACCATGGACCGCCTGTA





CACTCCTG

TACTCCATCA

CCGCCTGTACTT

CTTTGTGATGGAGTACGTGAATGGG





PROM1
NM_006017
1917
CTATGACAGG
1918
CTCCAACCAT
1919
ACCCGAGGCTGT
1920
CTATGACAGGCATGCCACCCCGACCACCCGAGGCTGTGTCTC





CATGCCACC

GAGGAAGACG

GTCTCCAACAC

CAACACCGGAGGCGTCTTCCTCATGGTTGGAG





PROS1
NM_000313
1921
GCAGCACAGG
1922
CCCACCTATC
1923
CTCATCCTGACA
1924
GCAGCACAGGAATCTTCTTCTTGGCAGCTGCAGTCTGTCAGGA





AATCTTCTTC

CAACCTAATC

GACTGCAGCTGC

TGAGATATCAGATTAGGTTGGATAGGTGGG





TT

TG









PSCA
NM_005672
1925
ACCGTCATCA
1926
CGTGATGTTC
1927
CCTGTGAGTCAT
1928
ACCGTCATCAGCAAAGGCTGCAGCTTGAACTGCGTGGATGAC





GCAAAGGCT

TTCTTGCCC

CCACGCAGTTCA

TCACAGGACTACTACGTGGGCAAGAAGAACATCACG





PSMD13
NM_002817
1929
GGAGGAGCTC
1930
CGGATCCTGC
1931
CCTGAAGTGTCA
1932
GGAGGAGCTCTACACGAAGAAGTTGTGGCATCAGCTGACACT





TACACGAAGA

ACAAAATCA

GCTGATGCCACA

TCAGGTGCTTGATTTTGTGCAGGATCCG





AG











PTCH1
NM_000264
1933
CCACGACAAA
1934
TACTCGATGG
1935
CCTGAAACAAGG
1936
CCACGACAAAGCCGACTACATGCCTGAAACAAGGCTGAGAAT





GCCGACTAC

GCTCTGCTG

CTGAGAATCCCG

CCCGGCAGCAGAGCCCATCGAGTA





PTEN
NM_000314
1937
TGGCTAAGTG
1938
TGCACATATC
1939
CCTTTCCAGCTT
1940
TGGCTAAGTGAAGATGACAATCATGTTGCAGCAATTCACTGTA





AAGATGACAA

ATTACACCAG

TACAGTGAATTG

AAGCTGGAAAGGGACGAACTGGTGTAATGATATGTGCA





TCATG

TTCGT

CTGCA







PTGER3
NM_000957
1941
TAACTGGGGC
1942
TTGCAGGAAA
1943
CCTTTGCCTTCC
1944
TAACTGGGGCAACCTTTTCTTCGCCTCTGCCTTTGCCTTCCTG





AACCTTTTCT

AGGTGACTGT

TGGGGCTCTT

GGGCTCTTGGCGCTGACAGTCACCTTTTCCTGCAA





PTGS2
NM_000963
1945
GAATCATTCA
1946
CTGTACTGCG
1947
CCTACCACCAGC
1948
GAATCATTCACCAGGCAAATTGCTGGCAGGGTTGCTGGTGGTA





CCAGGCAAAT

GGTGGAACAT

AACCCTGCCA

GGAATGTTCCACCCGCAGTACAG





TG











PTH1R
NM_000316
1949
CGAGGTACAA
1950
GCGTGCCTTT
1951
CCAGTGCCAGTG
1952
CGAGGTACAAGCTGAGATCAAGAAATCTTGGAGCCGCTGGAC





GCTGAGATCA

CGCTTGAA

TCCAGCGGCT

ACTGGCACTGGACTTCAAGCGAAAGGCACGC





AGAA











PTHLH
NM_002820
1953
AGTGACTGGG
1954
AAGCCTGTTA
1955
TGACACCTCCAC
1956
AGTGACTGGGAGTGGGCTAGAAGGGGACCACCTGTCTGACAC





AGTGGGCTAG

CCGTGAATCG

AACGTCGCTGGA

CTCCACAACGTCGCTGGAGCTCGATTCACGGTAACAGGCTT





AA

A









PTK2
NM_005607
1957
GACCGGTCGA
1958
CTGGACATCT
1959
ACCAGGCCCGTC
1960
GACCGGTCGAATGATAAGGTGTACGAGAATGTGACGGGCCTG





ATGATAAGGT

CGATGACAGC

ACATTCTCGTAC

GTGAAAGCTGTCATCGAGATGTCCAG





PTK2B
NM_004103
1961
CAAGCCCAGC
1962
GAACCTGGAA
1963
CTCCGCAAACCA
1964
CAAGCCCAGCCGACCTAAGTACAGACCCCCTCCGCAAACCAA





CGACCTAAG

CTGCAGCTTT

ACCTCCTGGCT

CCTCCTGGCTCCAAAGCTGCAGTTCCAGGTTC







G









PTK6
NM_005975
1965
GTGCAGGAAA
1966
GCACACACGA
1967
AGTGTCTGCGTC
1968
GTGCAGGAAAGGTTCACAAATGTGGAGTGTCTGCGTCCAATAC





GGTTCACAAA

TGGAGTAAGG

CAATACACGCGT

ACGCGTGTGCTCCTCTCCTTACTCCATCGTGTGTGC





PTK7
NM_002821
1969
TCAGAGGACT
1970
CATACACCTC
1971
CGCAAGGTCCCA
1972
TCAGAGGACTCACGGTTCGAGGTCTTCAAGAATGGGACCTTGC





CACGGTTCG

CACGCTGTTG

TTCTTGAAGACC

GCATCAACAGCGTGGAGGTGTATG





PTPN1
NM_002827
1973
AATGAGGAAG
1974
CTTCGATCAC
1975
CTGATCCAGACA
1976
AATGAGGAAGTTTCGGATGGGGCTGATCCAGACAGCCGACCA





TTTCGGATGG

AGCCAGGTAG

GCCGACCAGCT

GCTGCGCTTCTCCTACCTGGCTGTGATCGAAG





PTPRK
NM_002844
1977
TCAAACCCTC
1978
AGCAGCCAGT
1979
CCCCATCGTTGT
1980
TCAAACCCTCCCAGTGCTGGCCCCATCGTTGTACATTGCAGTG





CCAGTGCT

TCGTCCAG

ACATTGCAGTGC

CTGGTGCTGGACGAACTGGCTGCT





PTTG1
NM_004219
1981
GGCTACTCTG
1982
GCTTCAGCCC
1983
CACACGGGTGCC
1984
GGCTACTCTGATCTATGTTGATAAGGAAAATGGAGAACCAGGC





ATCTATGTTG

ATCCTTAGCA

TGGTTCTCCA

ACCCGTGTGGTTGCTAAGGATGGGCTGAAGC





ATAAGGAA











PYCARD
NM_013258
1985
CTTTATAGAC
1986
AGCATCCAGC
1987
ACGTTTGTGACC
1988
CTTTATAGACCAGCACCGGGCTGCGCTTATCGCGAGGGTCAC





CAGCACCGGG

AGCCACTC

CTCGCGATAAGC

AAACGTTGAGTGGCTGCTGGATGCT





RAB27A
NM_004580
1989
TGAGAGATTA
1990
CCGGATGCTT
1991
ACAAATTGCTTC
1992
TGAGAGATTAATGGGCATTGTGTACAAATTGCTTCTCACCATC





ATGGGCATTG

TATTCGTAGG

TCACCATCCCCA

CCCATTAGACCTACGAATAAAGCATCCGG





TG



TT







RAB30
NM_014488
1993
TAAAGGCTGA
1994
CTCCCCAGCA
1995
CCATCAGGGCAG
1996
TAAAGGCTGAGGCACGGAGAAGAAAAGGAATCAGCAACTGCC





GGCACGGA

TCTCATGG

TTGCTGATTCCT

CTGATGGGCCATGAGATGCTGGGGAG





RAB31
NM_006868
1997
CTGAAGGACC
1998
ATGCAAAGCC
1999
CTTCTCAAAGTG
2000
CTGAAGGACCCTACGCTCGGTGGCCTGGCACCTCACTTTGAG





CTACGCTCG

AGTGTGCTC

AGGTGCCAGGCC

AAGAGTGAGCACACTGGCTTTGCAT





RAD21
NM_006265
2001
TAGGGATGGT
2002
TCGCGTACAC
2003
CACTTAAAACGA
2004
TAGGGATGGTATCTGAAACAACAATGGTCACCCTCTTGAGATT





ATCTGAAACA

CTCTGCTC

ATCTCAAGAGGG

CGTTTTAAGTGTAATTCCATAATGAGCAGAGGTGTACGCGA





ACA



TGACCA







RAD51
NM_002875
2005
AGACTACTCG
2006
AGCATCCGCA
2007
CTTTCAGCCAGG
2008
AGACTACTCGGGTCGAGGTGAGCTTTCAGCCAGGCAGATGCA





GGTCGAGGTG

GAAACCTG

CAGATGCACTTG

CTTGGCCAGGTTTCTGCGGATGCT





RAD9A
NM_004584
2009
GCCATCTTCA
2010
CGGTGTCTGA
2011
CTTTGCTGGACG
2012
GCCATCTTCACCATCAAGGACTCTTTGCTGGACGGCCACTTTG





CCATCAAGG

GAGTGTGGC

GCCACTTTGTCT

TCTTGGCCACACTCTCAGACACCG





RAF1
NM_002880
2013
CGTCGTATGC
2014
TGAAGGCGTG
2015
TCCAGGATGCCT
2016
CGTCGTATGCGAGAGTCTGTTTCCAGGATGCCTGTTAGTTCTC





GAGAGTCTGT

AGGTGTAGAA

GTTAGTTCTCAG

AGCACAGATATTCTACACCTCACGCCTTCA









CA







RAGE
NM_014226
2017
ATTAGGGGAC
2018
GGGTGGAGAT
2019
CCGGAGTGTCTA
2020
ATTAGGGGACTTTGGCTCCTGCCGGAGTGTCTATTCCAAGCAG





TTTGGCTCCT

GTATTCCGTG

TTCCAAGCAGCC

CCGTACACGGAATACATCTCCACCC





RALA
NM_005402
2021
TGGTCCTGAA
2022
CCCCATTTCA
2023
TTGTGTTTCTTG
2024
TGGTCCTGAATGTAGCGTGTAAGCTTGTGTTTCTTGGGCAGTC





TGTAGCGTGT

CCTCTTCAAT

GGCAGTCTTTCT

TTTCTTGAAATTGAAGAGGTGAAATGGGG









TGAA







RALBP1
NM_006788
2025
GGTGTCAGAT
2026
TTCGATATTG
2027
TGCTGTCCTGTC
2028
GGTGTCAGATATAAATGTGCAAATGCCTTCTTGCTGTCCTGTC





ATAAATGTGC

CCAGCAGCTA

GGTCTCAGTACG

GGTCTCAGTACGTTCACTTTATAGCTGCTGGCAATATCGAA





AAATGC

TAAA

TTCA







RAP1B
NM_
2029
TGACAGCGTG
2030
CTGAGCCAAG
2031
CACGCATGATGC
2032
TGACAGCGTGAGAGGTACTAGGTTTTGACAAGCTTGCATCATG



001010942

AGAGGTACTA

AACGACTAGC

AAGCTTGTCAAA

CGTGAGTATAAGCTAGTCGTTCTTGGCTCAG





GG

TT









RARB
NM_000965
2033
ATGAACCCTT
2034
GAGCTGGGTG
2035
TGTGCTCTGCTG
2036
ATGAACCCTTGACCCCAAGTTCAAGTGGGAACACAGCAGAGC





GACCCCAAGT

AGATGCTAGG

TGTTCCCACTTG

ACAGTCCTAGCATCTCACCCAGCTC





RASSF1
NM_007182
2037
AGGGCACGTG
2038
AAAGAGTGCA
2039
CACCACCAAGAA
2040
AGGGCACGTGAAGTCATTGAGGCCCTGCTGCGAAAGTTCTTG





AAGTCATTG

AACTTGCGG

CTTTCGCAGCAG

GTGGTGGATGACCCCCGCAAGTTTGCACTCTTT





RB1
NM_000321
2041
CGAAGCCCTT
2042
GGACTCTTCA
2043
CCCTTACGGATT
2044
CGAAGCCCTTACAAGTTTCCTAGTTCACCCTTACGGATTCCTG





ACAAGTTTCC

GGGGTGAAAT

CCTGGAGGGAAC

GAGGGAACATCTATATTTCACCCCTGAAGAGTCC





RECK
NM_021111
2045
GTCGCCGAGT
2046
GTGGGATGAT
2047
TCAAGTGTCCTT
2048
GTCGCCGAGTGTGCTTCTGTCAAGTGTCCTTCGCTCTTGGCAG





GTGCTTCT

GGGTTTGC

CGCTCTTGGCAG

CTGGATGCAAACCCATCATCCCAC





REG4
NM_032044
2049
TGCTAACTCC
2050
TGCTAGGTTT
2051
TCCTCTTCCTTT
2052
TGCTAACTCCTGCACAGCCCCGTCCTCTTCCTTTCTGCTAGCC





TGCACAGCC

CCCCTCTGAA

CTGCTAGCCTGG

TGGCTAAATCTGCTCATTATTTCAGAGGGGAAACCTAGCA









C







RELA
NM_021975
2053
CTGCCGGGAT
2054
CCAGGTTCTG
2055
CTGAGCTCTGCC
2056
CTGCCGGGATGGCTTCTATGAGGCTGAGCTCTGCCCGGACCG





GGCTTCTAT

GAAACTGTGG

CGGACCGCT

CTGCATCCACAGTTTCCAGAACCTGG







AT









RFX1
NM_002918
2057
TCCTCTCCAA
2058
CAGGCCCTGG
2059
TCCAATGGACCA
2060
TCCTCTCCAAGTTCGAGCCCGTGCTCCAATGGACCAAGCACTG





GTTCGAGCC

TACAGCAC

AGCACTGTGACA

TGACAACGTGCTGTACCAGGGCCTG





RGS10
NM_
2061
AGACATCCAC
2062
CCATTTGGCT
2063
AGTTCCAGCAGC
2064
AGACATCCACGACAGCGATGGCAGTTCCAGCAGCAGCCACCA



001005339

GACAGCGAT

GTGCTCTTG

AGCCACCAGAG

GAGCCTCAAGAGCACAGCCAAATGG





RGS7
NM_002924
2065
CAGGCTGCAG
2066
TTTGCTTGTG
2067
TGAAAATGAACT
2068
CAGGCTGCAGAGAGCATTTGCCCGGAAGTGGGAGTTCATTTTC





AGAGCATTT

CTTCTGCTTG

CCCACTTCCGGG

ATGCAAGCAGAAGCACAAGCAAA





RHOA
NM_001664
2069
TGGCATAGCT
2070
TGCCACAGCT
2071
AAATGGGCTCAA
2072
TGGCATAGCTCTGGGGTGGGCAGTTTTTTGAAAATGGGCTCAA





CTGGGGTG

GCATGAAC

CCAGAAAAGCCC

CCAGAAAAGCCCAAGTTCATGCAGCTGTGGCA





RHOB
NM_004040
2073
AAGCATGAAC
2074
CCTCCCCAAG
2075
CTTTCCAACCCC
2076
AAGCATGAACAGGACTTGACCATCTTTCCAACCCCTGGGGAAG





AGGACTTGAC

TCAGTTGC

TGGGGAAGACAT

ACATTTGCAACTGACTTGGGGAGG





C











RHOC
NM_175744
2077
CCCGTTCGGT
2078
GAGCACTCAA
2079
TCCGGTTCGCCA
2080
CCCGTTCGGTCTGAGGAAGGCCGGGACATGGCGAACCGGATC





CTGAGGAA

GGTAGCCAAA

TGTCCCG

AGTGCCTTTGGCTACCTTGAGTGCTC







GG









RLN1
NM_006911
2081
AGCTGAAGGC
2082
TTGGAATCCT
2083
TGAGAGGCAACC
2084
AGCTGAAGGCAGCCCTATCTGAGAGGCAACCATCATTACCAG





AGCCCTATC

TTAATGCAGG

ATCATTACCAGA

AGCTACAGCAGTATGTACCTGCATTAAAGGATTCCAA







T

GC







RND3
NM_005168
2085
TCGGAATTGG
2086
CTGGTTACTC
2087
TTTTAAGCCTGA
2088
TCGGAATTGGACTTGGGAGGCGCGGTGAGGAGTCAGGCTTAA





ACTTGGGAG

CCCTCCAACA

CTCCTCACCGCG

AACTTGTTGGAGGGGAGTAACCAG





RNF114
NM_018683
2089
TGACAGGGGA
2090
GGAAGACAGC
2091
CCAGGTCAGCCC
2092
TGACAGGGGAAGTGGGTCCCCAGGTCAGCCCTTCTCTTCCCT





AGTGGGTC

TTTGGCAAGA

TTCTCTTCCCTT

TTGGGCTCTTGCCAAAGCTGTCTTCC





ROBO2
NM_002942
2093
CTACAAGGCC
2094
CACCAGTGGC
2095
CTGTACCATCCA
2096
CTACAAGGCCCAGCCAACCAAACGCTGGCAGTGGATGGTACA





CAGCCAAC

TTTACATTTC

CTGCCAGCGTTT

GCGTTACTGAAATGTAAAGCCACTGGTG







AG









RRM1
NM_001033
2097
GGGCTACTGG
2098
CTCTCAGCAT
2099
CATTGGAATTGC
2100
GGGCTACTGGCAGCTACATTGCTGGGACTAATGGCAATTCCAA





CAGCTACATT

CGGTACAAGG

CATTAGTCCCAG

TGGCCTTGTACCGATGCTGAGAG









C







RRM2
NM_001034
2101
CAGCGGGATT
2102
ATCTGCGTTG
2103
CCAGCACAGCCA
2104
CAGCGGGATTAAACAGTCCTTTAACCAGCACAGCCAGTTAAAA





AAACAGTCCT

AAGCAGTGAG

GTTAAAAGATGC

GATGCAGCCTCACTGCTTCAACGCAGAT









A







S100P
NM_005980
2105
AGACAAGGAT
2106
GAAGTCCACC
2107
TTGCTCAAGGAC
2108
AGACAAGGATGCCGTGGATAAATTGCTCAAGGACCTGGACGC





GCCGTGGATA

TGGGCATCTC

CTGGACGCCAA

CAATGGAGATGCCCAGGTGGACTTC





A











SAT1
NM_002970
2109
CCTTTTACCA
2110
ACAATGCTGT
2111
TCCAGTGCTCTT
2112
CCTTTTACCACTGCCTGGTTGCAGAAGTGCCGAAAGAGCACTG





CTGCCTGGTT

GTCCTTCCG

TCGGCACTTCTG

GACTCCGGAAGGACACAGCATTGT





SCUBE2
NM_020974
2113
TGACAATCAG
2114
TGTGACTACA
2115
CAGGCCCTCTTC
2116
TGACAATCAGCACACCTGCATTCACCGCTCGGAAGAGGGCCT





CACACCTGCA

GCCGTGATCC

CGAGCGGT

GAGCTGCATGAATAAGGATCACGGCTGTAGTCACA





T

TTA









SDC1
NM_002997
2117
GAAATTGACG
2118
AGGAGCTAAC
2119
CTCTGAGCGCCT
2120
GAAATTGACGAGGGGTGTCTTGGGCAGAGCTGGCTCTGAGCG





AGGGGTGTCT

GGAGAACCTG

CCATCCAAGG

CCTCCATCCAAGGCCAGGTTCTCCGTTAGCTCCT





SDC2
NM_002998
2121
GGATTGAAGT
2122
ACCAGCCACA
2123
AACTCCATCTCC
2124
GGATTGAAGTGGCTGGAAAGAGTGATGCCTGGGGAAGGAGAT





GGCTGGAAAG

GTACCCTCA

TTCCCCAGGCAT

GGAGTTATGAGGGTACTGTGGCTGGT





SDHC
NM_003001
2125
CTTCCCTCGG
2126
TTCCCTCCTG
2127
TTACATCCTCCC
2128
CTTCCCTCGGGTCTCAGGCATTTACATCCTCCCTCTCCCCGCA





GTCTCAGG

GTAAAGGTCA

TCTCCCCGCAAT

ATCTGACCTTTACCAGGAGGGAA





SEC14L1
NM_
2129
AGGGTTCCCA
2130
GCAGGCATGC
2131
CGGGCTTCTACA
2132
AGGGTTCCCATGTGACCAGGTGGCCGGGCTTCTACATCCTGC



001039573

TGTGACCAG

TGTGGAAT

TCCTGCAGTGG

AGTGGAAATTCCACAGCATGCCTGC





SEC23A
NM_006364
2133
CGTGTGCATT
2134
CCCATTACCA
2135
TCCTGGAGATGA
2136
CGTGTGCATTAGATCAGACAGGTCTCCTGGAGATGAAATGCTG





AGATCAGACA

TGTATCCTCC

AATGCTGTCCCA

TCCCAACCTTACTGGAGGATACATGGTAATGGG





GG

AG









SEMA3A
NM_006080
2137
TTGGAATGCA
2138
CTCTTCATTT
2139
TTGCCAATAGAC
2140
TTGGAATGCAGTCCGAAGTCGCAGAGAGCGCTGGTCTATTGG





GTCCGAAGT

CGCCTCTGGA

CAGCGCTCTCTG

CAATTCCAGAGGCGAAATGAAGAG





SEPT9
NM_006640
2141
CAGTGACCAC
2142
CTTCGATGGT
2143
TTGCCAATAGAC
2144
CAGTGACCACGAGTACCAGGTCAACGGCAAGAGGATCCTTGG





GAGTACCAGG

ACCCCACTTG

CAGCGCTCTCTG

GAGGAAGACCAAGTGGGGTACCATCGAAG





SERPINA3
NM_001085
2145
GTGTGGCCCT
2146
CCCTGTGCAT
2147
AGGGAATCGCTG
2148
GTGTGGCCCTGTCTGCTTATCCTTGGAAGGTGACAGCGATTCC





GTCTGCTTA

GTGAGAGCTA

TCACCTTCCAAG

CTGTGTAGCTCTCACATGCACAGGG







C









SERPINB5
NM_002639
2149
CAGATGGCCA
2150
GGCAGCATTA
2151
AGCTGACAACAG
2152
CAGATGGCCACTTTGAGAACATTTTAGCTGACAACAGTGTGAA





CTTTGAGAAC

ACCACAAGGA

TGTGAACGACCA

CGACCAGACCAAAATCCTTGTGGTTAATGCTGCC





ATT

TT

GACC







SESN3
NM_144665
2153
GACCCTGGTT
2154
GAGCTCGGAA
2155
TGCTCTTCTCCT
2156
GACCCTGGTTTTGGGTATGAAGACTTTGCCAGACGAGGAGAA





TTGGGTATGA

TGTTGGCA

CGTCTGGCAAAG

GAGCATTTGCCAACATTCCGAGCTC





SFRP4
NM_003014
2157
TACAGGATGA
2158
GTTGTTAGGG
2159
CCTGGGACAGCC
2160
TACAGGATGAGGCTGGGCATTGCCTGGGACAGCCTATGTAAG





GGCTGGGC

CAAGGGGC

TATGTAAGGCCA

GCCATGTGCCCCTTGCCCTAACAAC





SH3RF2
NM_152550
2161
CCATCACAAC
2162
CACTGGGGTG
2163
AACCGGATGGTC
2164
CCATCACAACAGCCTTGAACACTCTCAACCGGATGGTCCATTC





AGCCTTGAAC

CTGATCTCTA

CATTCTCCTTCA

TCCTTCAGGGCGCCATATGGTAGAGATCAGCACCCCAGTG





SH3YL1
NM_015677
2165
CCTCCAAAGC
2166
CTTTGAGAGC
2167
CACAGCAGTCAT
2168
CCTCCAAAGCCATTGTCAAGACCACAGCAGTCATCTGCACCAG





CATTGTCAAG

CAGAGTTCAG

CTGCACCAGTCC

TCCAGCTGAACTCTGGCTCTCAAAG







C









SHH
NM_000193
2169
GTCCAAGGCA
2170
GAAGCAGCCT
2171
CACCGAGTTCTC
2172
GTCCAAGGCACATATCCACTGCTCGGTGAAAGCAGAGAACTC





CATATCCACT

CCCGATTT

TGCTTTCACCGA

GGTGGCGGCCAAATCGGGAGGCTGCTTC





G











SHMT2
NM_005412
2173
AGCGGGTGCT
2174
ATGGCACTTC
2175
CCATCACTGCCA
2176
AGCGGGTGCTAGAGCTTGTATCCATCACTGCCAACAAGAACAC





AGAGCTTGTA

GGTCTCCA

ACAAGAACACCT

CTGTCCTGGAGACCGAAGTGCCAT









G







SIM2
NM_005069
2177
GATGGTAGGA
2178
CACAAGGAGC
2179
CGCCTCTCCACG
2180
GATGGTAGGAAGGGATGTGCCCGCCTCTCCACGCACTCAGCT





AGGGATGTGC

TGTGAATGAG

CACTCAGCTAT

ATACCTCATTCACAGCTCCTTGTG







G









SIPA1L1
NM_015556
2181
CTAGGACAGC
2182
CATAACCGTA
2183
CGCCACAATGCC
2184
CTAGGACAGCTTGGCTTCCATGTCAACTATGAGGGCATTGTGG





TTGGCTTCCA

GGGCTCCACA

CTCATAGTTGAC

CGGATGTGGAGCCCTACGGTTATG





SKIL
NM_005414
2185
AGAGGCTGAA
2186
CTATCGGCCT
2187
CCAATCTCTGCC
2188
AGAGGCTGAATATGCAGGACAGTTGGCAGAACTGAGGCAGAG





TATGCAGGAC

CAGCATGG

TCAGTTCTGCCA

ATTGGACCATGCTGAGGCCGATAG





A











SLC22A3
NM_021977
2189
ATCGTCAGCG
2190
CAGGATGGCT
2191
CAGCATCCACGC
2192
ATCGTCAGCGAGTTTGACCTTGTCTGTGTCAATGCGTGGATGC





AGTTTGACCT

TGGGTGAG

ATTGACACAGAC

TGGACCTCACCCAAGCCATCCTG





SLC25A21
NM_030631
2193
AAGTGTTTTT
2194
GGCCGATCGA
2195
TCATGGTGCTGC
2196
AAGTGTTTTTCCCCCTTGAGATAATGGATATTTGCTATGCAGC





CCCCCTTGAG

TAGTCTCTCT

ATAGCAAATATC

ACCATGAAGAAGAGAGACTATCGATCGGCC





AT

T

CA







SLC44A1
NM_080546
2197
AGGACCGTAG
2198
ATCCCATCCC
2199
TACCATGGCTGC
2200
AGGACCGTAGCTGCACAGACATACCATGGCTGCTGCTCTTCAT





CTGCACAGAC

AATGCAGA

TGCTCTTCATCC

CCTCTTCTGCATTGGGATGGGAT





SMAD4
NM_005359
2201
GGACATTACT
2202
ACCAATACTC
2203
TGCATTCCAGCC
2204
GGACATTACTGGCCTGTTCACAATGAGCTTGCATTCCAGCCTC





GGCCTGTTCA

AGGAGCAGGA

TCCCATTTCCA

CCATTTCCAATCATCCTGCTCCTGAGTATTGGT





CA

TGA









SMARCC2
NM_003075
2205
TACCGACTGA
2206
GACATCACCC
2207
TATCTTACCTCT
2208
TACCGACTGAACCCCCAAGAGTATCTTACCTCTACCGCCTGCC





ACCCCCAA

GCTAGGTTTC

ACCGCCTGCCGC

GCCGAAACCTAGCGGGTGATGTC





SMARCD1
NM_003076
2209
CCGAGTTAGC
2210
CCTTTGTGCC
2211
CCCACCCTTGCT
2212
CCGAGTTAGCATATCCCAGGCTCGCAGACTCAACACAGCAAG





ATATCCCAGG

CAGCTGTC

GTGTTGAGTCTG

GGTGGGAGACAGCTGGGCACAAAGG





SMO
NM_005631
2213
GGCATCCAGT
2214
CGCGATGTAG
2215
CTTCACAGAGGC
2216
GGCATCCAGTGCCAGAACCCGCTCTTCACAGAGGCTGAGCAC





GCCAGAAC

CTGTGCAT

TGAGCACCAGGA

CAGGACATGCACAGCTACATCGCG





SNAI1
NM_005985
2217
CCCAATCGGA
2218
GTAGGGCTGC
2219
TCTGGATTAGAG
2220
CCCAATCGGAAGCCTAACTACAGCGAGCTGCAGGACTCTAAT





AGCCTAACTA

TGGAAGGTAA

TCCTGCAGCTCG

CCAGAGTTTACCTTCCAGCAGCCCTAC









C




SNRPB2
NM_003092
2221
CGTTTCCTGC
2222
AGGTAGAAGG
2223
CCCACCTAAGGC
2224
CGTTTCCTGCTTTTGGTTCTTACAGTAGTCGGCGTAGGCCTTA





TTTTGGTTCT

CGCACGAA

CTACGCCGACTA

GGTGGGTTCGTGCGCCTTCTACCT





SOD1
NM_000454
2225
TGAAGAGAGG
2226
AATAGACACA
2227
TTTGTCAGCAGT
2228
TGAAGAGAGGCATGTTGGAGACTTGGGCAATGTGACTGCTGA





CATGTTGGAG

TCGGCCACAC

CACATTGCCCAA

CAAAGATGGTGTGGCCGATGTGTCTATT





SORBS1
NM_015385
2229
GCAGATGAGT
2230
AGCGAGTGAA
2231
ATTTCCATTGGC
2232
GCAGATGAGTGGAGGCTTTCTTCCAGTGCTGATGCCAATGGAA





GGAGGCTTTC

GAGGGCTG

ATCAGCACTGGA

ATGCCCAGCCCTCTTCACTCGCT





SOX4
NM_003107
2233
AGATGATCTC
2234
GCGCCCTTCA
2235
CGAGTCCAGCAT
2236
AGATGATCTCGGGAGACTGGCTCGAGTCCAGCATCTCCAACC





GGGAGACTGG

GTAGGTGA

CTCCAACCTGGT

TGGTTTTCACCTACTGAAGGGCGC





SPARC
NM_003118
2237
TCTTCCCTGT
2238
AGCTCGGTGT
2239
TGGACCAGCACC
2240
TCTTCCCTGTACACTGGCAGTTCGGCCAGCTGGACCAGCACC





ACACTGGCAG

GGGAGAGGTA

CCATTGACGG

CCATTGACGGGTACCTCTCCCACACCGAGCT





TTC











SPARCL1
NM_004684
2241
GGCACAGTGC
2242
GATTGAGCTC
2243
ACTTCATCCCAA
2244
GGCACAGTGCAAGTGATGACTACTTCATCCCAAGCCAGGCCTT





AAGTGATGA

TCTCGGCCT

GCCAGGCCTTTC

TCTGGAGGCCGAGAGAGCTCAATC





SPDEF
NM_012391
2245
CCATCCGCCA
2246
GGGTGCACGA
2247
ATCATCCGGAAG
2248
CCATCCGCCAGTATTACAAGAAGGGCATCATCCGGAAGCCAG





GTATTACAAG

ACTGGTAGA

CCAGACATCTCC

ACATCTCCCAGCGCCTCGTCTACCAGTTCGTGCACCC





SPINK1
NM_003122
2249
CTGCCATATG
2250
GTTGAAAACT
2251
ACCACGTCTCTT
2252
CTGCCATATGACCCTTCCAGTCCCAGGCTTCTGAAGAGACGTG





ACCCTTCCAG

GCACCGCAC

CAGAAGCCTGGG

GTAAGTGCGGTGCAGTTTTCAAC





SPINT1
NM_003710
2253
ATTCCCAGCA
2254
AGATGGCTAC
2255
CTGTCGCAGTGT
2256
ATTCCCAGCACAGGCTCTGTGGAGATGGCTGTCGCAGTGTTC





CAGGCTCTGT

CACCACCACA

TCCTGGTCATCT

CTGGTCATCTGCATTGTGGTGGTGGTAGCCATCT







A

GC







SPP1
NM_
2257
TCACACATGG
2258
GTTCAGGTCC
2259
TGAATGGTGCAT
2260
TCACACATGGAAAGCGAGGAGTTGAATGGTGCATACAAGGCC



001040058

AAAGCGAGG

TGGGCAAC

ACAAGGCCATCC

ATCCCCGTTGCCCAGGACCTGAAC





SOLE
NM_003129
2261
ATTTTCGAGG
2262
CCTGAGCAAG
2263
TGGGCAAGAAAA
2264
ATTTTCGAGGCCAAAAAATCATTTTACTGGGCAAGAAAAACAT





CCAAAAAATC

GATATTCACG

ACATCTCATTCC

CTCATTCCTTTGTCGTGAATATCCTTGCTCAGG









TTTG







SRC
NM_005417
2265
TGAGGAGTGG
2266
CTCTCGGGTT
2267
AACCGCTCTGAC
2268
TGAGGAGTGGTATTTTGGCAAGATCACCAGACGGGAGTCAGA





TATTTTGGCA

CTCTGCATTG

TCCCGTCTGGTG

GCGGTTACTGCTCAATGCAGAGAACCCGAGAG





AGA

A









SRD5A1
NM_001047
2269
GGGCTGGAAT
2270
CCATGACTGC
2271
CCTCTCTCGGAG
2272
GGGCTGGAATCTGTCTAGGAGCCCTCTCTCGGAGGCCACAGA





CTGTCTAGGA

ACAATGGCT

GCCACAGAGGCT

GGCTGGGGGTAGCCATTGTGCAGTCATGG





SRD5A2
NM_000348
2273
GTAGGTCTCC
2274
TCCCTGGAAG
2275
AGACACCACTCA
2276
GTAGGTCTCCTGGCGTTCTGCCAGCTGGCCTGGGGATTCTGA





TGGCGTTCTG

GGTAGGAGTA

GAATCCCCAGGC

GTGGTGTCTGCTTAGAGTTTACTCCTACCCTTCCAGGGA







A









ST5
NM_005418
2277
CCTGTCCTGC
2278
CAGCTGCACA
2279
AGTCACGAGCAC
2280
CCTGTCCTGCCAGAGCATGGATGAAGTTTCGCTGGGTGCTCGT





CAGAGCAT

AAACTGGC

CCAGCGAAACTT

GACTGGCCAGTTTTGTGCAGCTG





STAT1
NM_007315
2281
GGGCTCAGCT
2282
ACATGTTCAG
2283
TGGCAGTTTTCT
2284
GGGCTCAGCTTTCAGAAGTGCTGAGTTGGCAGTTTTCTTCTGT





TTCAGAAGTG

CTGGTCCACA

TCTGTCACCAAA

CACCAAAAGAGGTCTCAATGTGGACCAGCTGAACATGT









A







STAT3
NM_003150
2285
TCACATGCCA
2286
CTTGCAGGAA
2287
TCCTGGGAGAGA
2288
TCACATGCCACTTTGGTGTTTCATAATCTCCTGGGAGAGATTG





CTTTGGTGTT

GCGGCTATAC

TTGACCAGCA

ACCAGCAGTATAGCCGCTTCCTGCAAG





STAT5A
NM_003152
2289
GAGGCGCTCA
2290
GCCAGGAACA
2291
CGGTTGCTCTGC
2292
GAGGCGCTCAACATGAAATTCAAGGCCGAAGTGCAGAGCAAC





ACATGAAATT

CGAGGTTCTC

ACTTCGGCCT

CGGGGCCTGACCAAGGAGAACCTCGTGTTCCTGGC





C











STAT5B
NM_012448
2293
CCAGTGGTGG
2294
GCAAAAGCAT
2295
CAGCCAGGACAA
2296
CCAGTGGTGGTGATCGTTCATGGCAGCCAGGACAACAATGCG





TGATCGTTCA

TGTCCCAGAG

CAATGCGACGG

ACGGCCACTGTTCTCTGGGACAATGCTTTTGC







A









STMN1
NM_005563
2297
AATACCCAAC
2298
GGAGACAATG
2299
CACGTTCTCTGC
2300
AATACCCAACGCACAAATGACCGCACGTTCTCTGCCCCGTTTC





GCACAAATGA

CAAACCACAC

CCCGTTTCTTG

TTGCCCCAGTGTGGTTTGCATTGTCTCC





STS
NM_000351
2301
GAAGATCCCT
2302
GGATGATGTT
2303
CTGCGTGGCTCT
2304
GAAGATCCCTTTCCTCCTACTGTTCTTTCTGTGGGAAGCCGAG





TTCCTCCTAC

CGGCCTTGAT

CGGCTTCCCA

AGCCACGCAGCATCAAGGCCGAACATCATCC





TGTTC











SULF1
NM_015170
2305
TGCAGTTGTA
2306
TCTCAAGAAT
2307
TACCGTGCCAGC
2308
TGCAGTTGTAGGGAGTCTGGTTACCGTGCCAGCAGAAGCCAA





GGGAGTCTGG

TGCCGTTGAC

AGAAGCCAAAG

AGAAAGAGTCAACGGCAATTCTTGAGA





SUMO1
NM_003352
2309
GTGAAGCCAC
2310
CCTTCCTTCT
2311
CTGACCAGGAGG
2312
GTGAAGCCACCGTCATCATGTCTGACCAGGAGGCAAAACCTTC





CGTCATCATG

TATCCCCCAA

CAAAACCTTCAA

AACTGAGGACTTGGGGGATAAGAAGGAAGG







GT

CTGA







SVIL
NM_003174
2313
ACTTGCCCAG
2314
GACACCATCC
2315
ACCCCAGGACTG
2316
ACTTGCCCAGCACAAGGAAGACCCCAGGACTGATGTCAAGGC





CACAAGGA

GTGTCACATC

ATGTCAAGGCAT

ATACGATGTGACACGGATGGTGTC





TAF2
NM_003184
2317
GCGCTCCACT
2318
CTTGTGCTCA
2319
AGCCTCCAAACA
2320
GCGCTCCACTCTCAGTCTTTACTAAGGAATCTACAGCCTCCAA





CTCAGTCTTT

TGGTGATGGT

CAGTGACCACCA

ACACAGTGACCACCATCACCACCATCACCATGAGCACAAG





TARP
NM_
2321
GAGCAACACG
2322
GGCACCGTTA
2323
TCTTCATGGTGT
2324
GAGCAACACGATTCTGGGATCCCAGGAGGGGAACACCATGAA



001003799

ATTCTGGGA

ACCAGCTAAA

TCCCCTCCTGG

GACTAACGACACATACATGAAATTTAGCTGGTTAACGGTGCC







T









TBP
NM_003194
2325
GCCCGAAACG
2326
CGTGGCTCTC
2327
TACCGCAGCAAA
2328
GCCCGAAACGCCGAATATAATCCCAAGCGGTTTGCTGCGGTA





CCGAATATA

TTATCCTCAT

CCGCTTGGG

ATCATGAGGATAAGAGAGCCACG







GAT









TFDP1
NM_007111
2329
TGCGAAGTGC
2330
GCCTTCCAGA
2331
CGCACCAGCATG
2332
TGCGAAGTGCTTTTGTTTGTTTGTTTTCGTTTGGTTAAAGCTT





TTTTGTTTGT

CAGTCTCCAT

GCAATAAGCTTT

ATTGCCATGCTGGTGCGGCTATGGAGACTGTCTGGAAGGC





TFF1
NM_003225
2333
GCCCTCCCAG
2334
CGTCGATGGT
2335
TGCTGTTTCGAC
2336
GCCCTCCCAGTGTGCAAATAAGGGCTGCTGTTTCGACGACAC





TGTGCAAAT

ATTAGGATAG

GACACCGTTCG

CGTTCGTGGGGTCCCCTGGTGCTTCTATCCTAATACCATCGAC







AAGCA



G





TFF3
NM_003226
2337
AGGCACTGTT
2338
CATCAGGCTC
2339
CAGAAGCGCTTG
2340
AGGCACTGTTCATCTCAGCTTTTCTGTCCCTTTGCTCCCGGCA





CATCTCAGTT

CAGATATGAA

CCGGGAGCAAAG

AGCGCTTCTGCTGAAAGTTCATATCTGGAGCCTGATG





TTTCT

CTTTC

G







TGFA
NM_003236
2341
GGTGTGCCAC
2342
ACGGAGTTCT
2343
TTGGCCTGTAAT
2344
GGTGTGCCACAGACCTTCCTACTTGGCCTGTAATCACCTGTGC





AGACCTTCCT

TGACAGAGTT

CACCTGTGCAGC

AGCCTTTTGTGGGCCTTCAAAACTCTGTCAAGAACTCCGT







TTGA

CTT







TGFB1I1
NM_
2345
GCTACTTTGA
2346
GGTCACCATC
2347
CAAGATGTGGCT
2348
GCTACTTTGAGCGCTTCTCGCCAAGATGTGGCTTCTGCAACCA



001042454

GCGCTTCTCG

TTGTGTCGG

TCTGCAACCAGC

GCCCATCCGACACAAGATGGTGACC





TGFB2
NM_003238
2349
ACCAGTCCCC
2350
CCTGGTGCTG
2351
TCCTGAGCCCGA
2352
ACCAGTCCCCCAGAAGACTATCCTGAGCCCGAGGAAGTCCCC





CAGAAGACTA

TTGTAGATGG

GGAAGTCCC

CCGGAGGTGATTTCCATCTACAACAGCACCAGG





TGFB3
NM_003239
2353
GGATCGAGCT
2354
GCCACCGATA
2355
CGGCCAGATGAG
2356
GGATCGAGCTCTTCCAGATCCTTCGGCCAGATGAGCACATTGC





CTTCCAGATC

TAGCGCTGTT

CACATTGCC

CAAACAGCGCTATATCGGTGGC





CT











TGFBR2
NM_003242
2357
AACACCAATG
2358
CCTCTTCATC
2359
TTCTGGGCTCCT
2360
AACACCAATGGGTTCCATCTTTCTGGGCTCCTGATTGCTCAAG





GGTTCCATCT

AGGCCAAACT

GATTGCTCAAGC

CACAGTTTGGCCTGATGAAGAGG





THBS2
NM_003247
2361
CAAGACTGGC
2362
CAGCGTAGGT
2363
TGAGTCTGCCAT
2364
CAAGACTGGCTACATCAGAGTCTTAGTGCATGAAGGAAAACAG





TACATCAGAG

TTGGTCATAG

GACCTGTTTTCC

GTCATGGCAGACTCAGGACCTATCTATGACCAAACCTACGCTG





TCTTAGTG

ATAGG

TTCAT







THY1
NM_006288
2365
GGACAAGACC
2366
TTGGAGGCTG
2367
CAAGCTCCCAAG
2368
GGACAAGACCCTCTCAGGCTGTCCCAAGCTCCCAAGAGCTTC





CTCTCAGGCT

TGGGTCAG

AGCTTCCAGAGC

CAGAGCTCTGACCCACAGCCTCCAA





TIAM1
NM_003253
2369
GTCCCTGGCT
2370
GGGCTCCCGA
2371
TGGAGCCCTTCT
2372
GTCCCTGGCTGAAAATGGCCTGGAGCCCTTCTCCCAAGATGG





GAAAATGG

AGTCTTCTA

CCCAAGATGGTA

TACCCTAGAAGACTTCGGGAGCCC





TIMP2
NM_003255
2373
TCACCCTCTG
2374
TGTGGTTCAG
2375
CCCTGGGACACC
2376
TCACCCTCTGTGACTTCATCGTGCCCTGGGACACCCTGAGCAC





TGACTTCATC

GCTCTTCTTC

CTGAGCACCA

CACCCAGAAGAAGAGCCTGAACCACA





GT

TG









TIMP3
NM_000362
2377
CTACCTGCCT
2378
ACCGAAATTG
2379
CCAAGAACGAGT
2380
CTACCTGCCTTGCTTTGTGACTTCCAAGAACGAGTGTCTCTGG





TGCTTTGTGA

GAGAGCATGT

GTCTCTGGACCG

ACCGACATGCTCTCCAATTTCGGT





TK1
NM_003258
2381
GCCGGGAAGA
2382
CAGCGGCACC
2383
CAAATGGCTTCC
2384
GCCGGGAAGACCGTAATTGTGGCTGCACTGGATGGGACCTTC





CCGTAATTGT

AGGTTCAG

TCTGGAAGGTCC

CAGAGGAAGCCATTTGGGGCCATCCTGAACCTGGTGCCGCTG









CA







TMPRSS2
NM_005656
2385
GGACAGTGTG
2386
CTCCCACGAG
2387
AAGCACTGTGCA
2388
GGACAGTGTGCACCTCAAAGACTAAGAAAGCACTGTGCATCAC





CACCTCAAAG

GAAGGTCC

TCACCTTGACCC

CTTGACCCTGGGGACCTTCCTCGTGGGAG





TMPRSS2
DQ204772
2389
GAGGCGGAGG
2390
ACTGGTCCTC
2391
TAAGGCTTCCTG
2392
GAGGCGGAGGCGGAGGGCGAGGGGCGGGGAGCGCCGCCTG


ERG A


GCGAG

ACTCACAACT

CCGCGCTCCA

GAGCGCGGCAGGAAGCCTTATCAGTTGTGAGTGAGGACCAGT





TMPRSS2
DQ204773
2393
GAGGCGGAGG
2394
TTCCTCGGGT
2395
CCTGGAATAACC
2396
GAGGCGGAGGGCGAGGGGCGGGGAGCGCCGCCTGGAGCGC


ERG B


GCGAG

CTCCAAAGAT

TGCCGCGC

GGCAGGTTATTCCAGGATCTTTGGAGACCCGAGGAA





TNF
NM_000594
2397
GGAGAAGGGT
2398
TGCCCAGACT
2399
CGCTGAGATCAA
2400
GGAGAAGGGTGACCGACTCAGCGCTGAGATCAATCGGCCCGA





GACCGACTCA

CGGCAAAG

TCGGCCCGACTA

CTATCTCGACTTTGCCGAGTCTGGGCA





TNFRS
NM_003844
2401
TGCACAGAGG
2402
TCTTCATCTG
2403
CAATGCTTCCAA
2404
TGCACAGAGGGTGTGGGTTACACCAATGCTTCCAACAATTTGT


F10A


GTGTGGGTTA

ATTTACAAGC

CAATTTGTTTGC

TTGCTTGCCTCCCATGTACAGCTTGTAAATCAGATGAAGA





C

TGTACATG

TTGCC







TNFRS
NM_003842
2405
CTCTGAGACA
2406
CCATGAGGCC
2407
CAGACTTGGTGC
2408
CTCTGAGACAGTGCTTCGATGACTTTGCAGACTTGGTGCCCTT


F10B


GTGCTTCGAT

CAACTTCCT

CCTTTGACTCC

TGACTCCTGGGAGCCGCTCATGAGGAAGTTGGGCCTCATGG





GACT











TNFRSF18
NM_148901
2409
CAGAAGCTGC
2410
CACCCACAGG
2411
CCTTCTCCTCTG
2412
CAGAAGCTGCCAGTTCCCCGAGGAAGAGCGGGGCGAGCGAT





CAGTTCCC

TCTCCCAG

CCGATCGCTC

CGGCAGAGGAGAAGGGGCGGCTGGGAGACCTGTGGGTG





TNFSF10
NM_003810
2413
CTTCACAGTG
2414
CATCTGCTTC
2415
AAGTACACGTAA
2416
CTTCACAGTGCTCCTGCAGTCTCTCTGTGTGGCTGTAACTTAC





CTCCTGCAGT

AGCTCGTTGG

GTTACAGCCACA

GTGTACTTTACCAACGAGCTGAAGCAGATG





CT

T

CA







TNFSF11
NM_003701
2417
AACTGCATGT
2418
TGACACCCTC
2419
ACATGACCAGGG
2420
AACTGCATGTGGGCTATGGGAGGGGTTGGTCCCTGGTCATGT





GGGCTATGG

TCCACTTCAG

ACCAACCCCTC

GCCCCTTCGCAGCTGAAGTGGAGAGGGTGTCA





TOP2A
NM_001067
2421
AATCCAAGGG
2422
GTACAGATTT
2423
CATATGGACTTT
2424
AATCCAAGGGGGAGAGTGATGACTTCCATATGGACTTTGACTC





GGAGAGTGAT

TGCCCGAGGA

GACTCAGCTGTG

AGCTGTGGCTCCTCGGGCAAAATCTGTAC









GC







TP53
NM_000546
2425
CTTTGAACCC
2426
CCCGGGACAA
2427
AAGTCCTGGGTG
2428
CTTTGAACCCTTGCTTGCAATAGGTGTGCGTCAGAAGCACCCA





TTGCTTGCAA

AGCAAATG

CTTCTGACGCAC

GGACTTCCATTTGCTTTGTCCCGGG









A







TP63
NM_003722
2429
CCCCAAGCAG
2430
GAATCGCACA
2431
CCCGGGTCTCAC
2432
CCCCAAGCAGTGCCTCTACAGTCAGTGTGGGCTCCAGTGAGA





TGCCTCTACA

GCATCAATAA

TGGAGCCCA

CCCGGGGTGAGCGTGTTATTGATGCTGTGCGATTC







CAC









TPD52
NM_005079
2433
GCCTGTGAGA
2434
ATGTGCTTGG
2435
TCTGCTACCCAC
2436
GCCTGTGAGATTCCTACCTTTGTTCTGCTACCCACTGCCAGAT





TTCCTACCTT

ACCTCGCTT

TGCCAGATGCTG

GCTGCAAGCGAGGTCCAAGCACAT





TG











TPM1
NM_
2437
TCTCTGAGCT
2438
GGCTCTAAGG
2439
TTCTCCAGCTGA
2440
TCTCTGAGCTCTGCATTTGTCTATTCTCCAGCTGACCCTGGTT



001018005

CTGCATTTGT

CAGGATGCTA

CCCTGGTTCTCT

CTCTCTCTTAGCATCCTGCCTTAGAGCC





C



C







TPM2
NM_213674
2441
AGGAGATGCA
2442
CCACCTCTTC
2443
CCAAGCACATCG
2444
AGGAGATGCAGCTGAAGGAGGCCAAGCACATCGCTGAGGATT





GCTGAAGGAG

ATATTTGCGG

CTGAGGATTCAG

CAGACCGCAAATATGAAGAGGTGG





TPP2
NM_003291
2445
TAACCGTGGC
2446
ATGCCAACGC
2447
ATCCTGTTCAGG
2448
TAACCGTGGCATCTACCTCCGAGATCCTGTTCAGGTGGCTGCA





ATCTACCTCC

CATGATCT

TGGCTGCACCTT

CCTTCAGATCATGGCGTTGGCAT





TPX2
NM_012112
2449
TCAGCTGTGA
2450
ACGGTCCTAG
2451
CAGGTCCCATTG
2452
TCAGCTGTGAGCTGCGGATACCGCCCGGCAATGGGACCTGCT





GCTGCGGATA

GTTTGAGGTT

CCGGGCG

CTTAACCTCAAACCTAGGACCGT







AAGA









TRA2A
NM_013293
2453
GCAAATCCAG
2454
CTTCACGAAG
2455
AACTGAGGCCAA
2456
GCAAATCCAGATCCCAACACTTGCCTTGGAGTGTTTGGCCTCA





ATCCCAACAC

ATCCCTCTCT

ACACTCCAAGGC

GTTTGTACACAACAGAGAGGGATCTTCGTGAAG







G









TRAF3IP2
NM_147200
2457
CCTCACAGGA
2458
CTGGGGCTGG
2459
TGGATCTGCCAA
2460
CCTCACAGGAACCGAGCAGGCCTGGATCTGCCAACCATAGAC





ACCGAGCA

GAATCATA

CCATAGACACGG

ACGGGATATGATTCCCAGCCCCAG





TRAM1
NM_014294
2461
CAAGAAAAGC
2462
ATGTCCGCGT
2463
AGTGCTGAGCCA
2464
CAAGAAAAGCACCAAGAGCCCCCCAGTGCTGAGCCACGAATT





ACCAAGAGCC

GATTCTGC

CGAATTCGTCC

CGTCCTGCAGAATCACGCGGACAT





TRAP1
NM_016292
2465
TTACCAGTGG
2466
TGTCCCGGTT
2467
TTCGGCGATTTC
2468
TTACCAGTGGCTTTCAGATGGTTCTGGAGTGTTTGAAATCGCC





CTTTCAGATG

CTAACTCCC

AAACACTCCAGA

GAAGCTTCGGGAGTTAGAACCGGGACA





G











TRIM14
NM_033220
2469
CATTCGCCTT
2470
CAAGGTACCT
2471
AACTGCCAGCTC
2472
CATTCGCCTTAAGGAAAGCATAAACTGCCAGCTCTCAGACCCT





AAGGAAAGCA

GGCTTGGTG

TCAGACCCTTCC

TCCAGCACCAAGCCAGGTACCTTG





TRO
NM_177556
2473
GCAACTGCCA
2474
TGGTGTGGAT
2475
CCACCCAAGGCC
2476
GCAACTGCCACCCATACAGCTACCACCCAAGGCCAAATTACCA





CCCATACAG

ACTGGCTGTC

AAATTACCAATG

ATGAGACAGCCAGTATCCACACCA





TRPC6
NM_004621
2477
CGAGAGCCAG
2478
TAGCCGTAGC
2479
CTTCTCCCAGCT
2480
CGAGAGCCAGGACTATCTGCTCATGGACTCGGAGCTGGGAGA





GACTATCTGC

AAGGCAGC

CCGAGTCCATG

AGACGGCTGCCCGCAAGCCCCGCTGCCTTGCTACGGCTA





TRPV6
NM_018646
2481
CCGTAGTCCC
2482
TCCTCACTGT
2483
ACTTTGGGGAGC
2484
CCGTAGTCCCTGCAACCTCATCTACTTTGGGGAGCACCCTTTG





TGCAACCTC

TCACACAGGC

ACCCTTTGTCCT

TCCTTTGCTGCCTGTGTGAACAGTGAGGA





TSTA3
NM_003313
2485
CAATTTGGAC
2486
CACCTCAAAG
2487
AACGTGCACATG
2488
CAATTTGGACTTCTGGAGGAAAAACGTGCACATGAACGACAAC





TTCTGGAGGA

GCCGAGTG

AACGACAACGTC

GTCCTGCACTCGGCCTTTGAGGTG





A











TUBB2A
NM_001069
2489
CGAGGACGAG
2490
ACCATGCTTG
2491
TCTCAGATCAAT
2492
CGAGGACGAGGCTTAAAAACTTCTCAGATCAATCGTGCATCCT





GCTTAAAAAC

AGGACAACAG

CGTGCATCCTTA

TAGTGAACTTCTGTTGTCCTCAAGCATGGT









GTGAA







TYMP
NM_001953
2493
CTATATGCAG
2494
CCACGAGTTT
2495
ACAGCCTGCCAC
2496
CTATATGCAGCCAGAGATGTGACAGCCACCGTGGACAGCCTG





CCAGAGATGT

CTTACTGAGA

TCATCACAGCC

CCACTCATCACAGCCTCCATTCTCAGTAAGAAACTCGTGG





GACA

ATGG









TYMS
NM_001071
2497
GCCTCGGTGT
2498
CGTGATGTGC
2499
CATCGCCAGCTA
2500
GCCTCGGTGTGCCTTTCAACATCGCCAGCTACGCCCTGCTCAC





GCCTTTCA

GCAATCATG

CGCCCTGCTC

GTACATGATTGCGCACATCACG





UAP1
NM_003115
2501
CTGGAGACGG
2502
GCCAAGCTTT
2503
TACCTGTAAACC
2504
CTGGAGACGGTCGTAGCTGCGGTCGCGCCGAGAAAGGTTTAC





TCGTAGCTG

GTAGAAATAG

TTTCTCGGCGCG

AGGTACATACATTACACCCCTATTTCTACAAAGCTTGGC







GG









UBE2C
NM_007019
2505
TGTCTGGCGA
2506
ATGGTCCCTA
2507
TCTGCCTTCCCT
2508
TGTCTGGCGATAAAGGGATTTCTGCCTTCCCTGAATCAGACAA





TAAAGGGATT

CCCATTTGAA

GAATCAGACAAC

CCTTTTCAAATGGGTAGGGACCAT









C







UBE2G1
NM_003342
2509
TGACACTGAA
2510
AAGCAGAGAG
2511
TTGTCCCACCAG
2512
TGACACTGAACGAGGTGGCTTTTGTCCCACCAGTGCCTCATCA





CGAGGTGGC

GAATCGCCT

TGCCTCATCAGT

GTGTGAGGCGATTCCTCTCTGCTT





UBE2T
NM_014176
2513
TGTTCTCAAA
2514
AGAGGTCAAC
2515
AGGTGCTTGGAG
2516
TGTTCTCAAATTGCCACCAAAAGGTGCTTGGAGACCATCCCTC





TTGCCACCAA

ACAGTTGCGA

ACCATCCCTCAA

AACATCGCAACTGTGTTGACCTCT





UGDH
NM_003359
2517
GAAACTCCAG
2518
CTCTGGGAAC
2519
TATACAGCACAC
2520
GAAACTCCAGAGGGCCAGAGAGCTGTGCAGGCCCTGTGTGCT





AGGGCCAGA

CCAGTGCTC

AGGGCCTGCACA

GTATATGAGCACTGGGTTCCCAGAG





UGT2B15
NM_001076
2521
AAGCCTGAAG
2522
CCTCCATTTA
2523
AAAGATGGGACT
2524
AAGCCTGAAGTGGAATGACTGAAAGATGGGACTCCTCCTTTAT





TGGAATGACT

AAACCCTCCA

CCTCCTTTATTT

TTCAGCATGGAGGGTTTTAAATGGAGG





G



CAGCA







UGT2B17
NM_001077
2525
TTGAGTTTGT
2526
TCCAGGTGAG
2527
ACCCGAAGGTGC
2528
TTGAGTTTGTCATGCGCCATAAAGGAGCCAAGCACCTTCGGGT





CATGCGCC

GTTGTGGG

TTGGCTCCTTTA

CGCAGCCCACAACCTCACCTGGA





UHRF1
NM_013282
2529
CTACAGGGGC
2530
GGTGTCATTC
2531
CGGCCATACCCT
2532
CTACAGGGGCAAACAGATGGAGGACGGCCATACCCTCTTCGA





AAACAGATGG

AGGCGGAC

CTTCGACTACGA

CTACGAGGTCCGCCTGAATGACACC





UTP23
NM_032334
2533
GATTGCACAA
2534
GGAAAGCAGA
2535
TCGAAATTGTCC
2536
GATTGCACAAAAATGCCAAGTTCGAAATTGTCCTCATTTCAAG





AAATGCCAAG

CATTCTGATC

TCATTTCAAGAA

AATGCAGTGAGTGGATCAGAATGTCTGCTTTCC







C

TGCA







VCAM1
NM_001078
2537
TGGCTTCAGG
2538
TGCTGTCGTG
2539
CAGGCACACACA
2540
TGGCTTCAGGAGCTGAATACCCTCCCAGGCACACACAGGTGG





AGCTGAATAC

ATGAGAAAAT

GGTGGGACACAA

GACACAAATAAGGGTTTTGGAACCACTATTTTCTCATCACGAC





C

AGTG

AT

AGCA





VCL
NM_003373
2541
GATACCACAA
2542
TCCCTGTTAG
2543
AGTGGCAGCCAC
2544
GATACCACAACTCCCATCAAGCTGTTGGCAGTGGCAGCCACG





CTCCCATCAA

GCGCATCAG

GGCGCC

GCGCCTCCTGATGCGCCTAACAGGGA





GCT











VCPIP1
NM_025054
2545
TTTCTCCCAG
2546
TGAATAGGGA
2547
TGGTCCATCCTC
2548
TTTCTCCCAGTACCATTCGTGATGGTCCATCCTCTGCACCTGC





TACCATTCGT

GCCTTGGTAG

TGCACCTGCTAC

TACACCTACCAAGGCTCCCTATTCA





G

G









VDR
NM_000376
2549
CCTCTCCTTC
2550
TCATTGCCAA
2551
CAGCATGAAGCT
2552
CCTCTCCTTCCAGCCTGAGTGCAGCATGAAGCTAACGCCCCTT





CAGCCTGAGT

ACACTTCGAG

AACGCCCCTTGT

GTGCTCGAAGTGTTTGGCAATGA





VEGFA
NM_003376
2553
CTGCTGTCTT
2554
GCAGCCTGGG
2555
TTGCCTTGCTGC
2556
CTGCTGTCTTGGGTGCATTGGAGCCTTGCCTTGCTGCTCTACC





GGGTGCATTG

ACCACTTG

TCTACCTCCACC

TCCACCATGCCAAGTGGTCCCAGGCTGC









A







VEGFB
NM_003377
2557
TGACGATGGC
2558
GGTACCGGAT
2559
CTGGGCAGCACC
2560
TGACGATGGCCTGGAGTGTGTGCCCACTGGGCAGCACCAAGT





CTGGAGTGT

CATGAGGATC

AAGTCCGGA

CCGGATGCAGATCCTCATGATCCGGTACC







TG









VEGFC
NM_005429
2561
CCTCAGCAAG
2562
AAGTGTGATT
2563
CCTCTCTCTCAA
2564
CCTCAGCAAGACGTTATTTGAAATTACAGTGCCTCTCTCTCAA





ACGTTATTTG

GGCAAAACTG

GGCCCCAAACCA

GGCCCCAAACCAGTAACAATCAGTTTTGCCAATCACACTT





AAATT

ATTG

GT







VIM
NM_003380
2565
TGCCCTTAAA
2566
GCTTCAACGG
2567
ATTTCACGCATC
2568
TGCCCTTAAAGGAACCAATGAGTCCCTGGAACGCCAGATGCG





GGAACCAATG

CAAAGTTCTC

TGGCGTTCCA

TGAAATGGAAGAGAACTTTGCCGTTGAAGC





A

TT









VTI1B
NM_006370
2569
ACGTTATGCA
2570
CCGATGGAGT
2571
CGAAACCCCATG
2572
ACGTTATGCACCCCTGTCTTTCCGAAACCCCATGATGTCTAAG





CCCCTGTCTT

TTAGCAAGGT

ATGTCTAAGCTT

CTTCGAAACTACCGGAAGGACCTTGCTAAACTCCATCGG









CG







WDR19
NM_025132
2573
GAGTGGCCCA
2574
GATGCTTGAG
2575
CCCCTCGACGTA
2576
GAGTGGCCCAGATGTCCATAAGAATGGGAGACATACGTCGAG





GATGTCCATA

GGCTTGGTT

TGTCTCCCATTC

GGGTTAACCAAGCCCTCAAGCATC





WFDC1
NM_021197
2577
ACCCCTGCTC
2578
ATACCTTCGG
2579
CTATGAGTGCCA
2580
ACCCCTGCTCTGTCCCTCGGGCTATGAGTGCCACATCCTGAG





TGTCCCTC

CCACGTCAC

CATCCTGAGCCC

CCCAGGTGACGTGGCCGAAGGTAT





WISP1
NM_003882
2581
AGAGGCATCC
2582
CAAACTCCAC
2583
CGGGCTGCATCA
2584
AGAGGCATCCATGAACTTCACACTTGCGGGCTGCATCAGCACA





ATGAACTTCA

AGTACTTGGG

GCACACGC

CGCTCCTATCAACCCAAGTACTGTGGAGTTTG





CA

TTGA









WNT5A
NM_003392
2585
GTATCAGGAC
2586
TGTCGGAATT
2587
TTGATGCCTGTC
2588
GTATCAGGACCACATGCAGTACATCGGAGAAGGCGCGAAGAC





CACATGCAGT

GATACTGGCA

TTCGCGCCTTCT

AGGCATCAAAGAATGCCAGTATCAATTCCGACA





ACATC

TT









WWOX
NM_016373
2589
ATCGCAGCTG
2590
AGCTCCCTGT
2591
CTGCTGTTTACC
2592
ATCGCAGCTGGTGGGTGTACACACTGCTGTTTACCTTGGCGAG





GTGGGTGTAC

TGCATGGACT

TTGGCGAGGCCT

GCCTTTCACCAAGTCCATGCAACAGGGAGCT







T

TTC







XIAP
NM_001167
2593
GCAGTTGGAA
2594
TGCGTGGCAC
2595
TCCCCAAATTGC
2596
GCAGTTGGAAGACACAGGAAAGTATCCCCAAATTGCAGATTTA





GACACAGGAA

TATTTTCAAG

AGATTTATCAAC

TCAACGGCTTTTATCTTGAAAATAGTGCCACGCA





AGT

A

GGC







XRCC5
NM_021141
2597
AGCCCACTTC
2598
AGCAGGATTC
2599
TCTGGCTGAAGG
2600
AGCCCACTTCAGCGTCTCCAGTCTGGCTGAAGGCAGTGTCAC





AGCGTCTC

ACACTTCCAA

CAGTGTCACCTC

CTCTGTTGGAAGTGTGAATCCTGCT







C









YY1
NM_003403
2601
ACCCGGGCAA
2602
GACCGAGAAC
2603
TTGATCTGCACC
2604
ACCCGGGCAACAAGAAGTGGGAGCAGAAGCAGGTGCAGATCA





CAAGAAGT

TCGCCCTC

TGCTTCTGCTCC

AGACCCTGGAGGGCGAGTTCTCGGTC





ZFHX3
NM_006885
2605
CTGTGGAGCC
2606
GGAGCAGGGT
2607
ACCTGGCCCAAC
2608
CTGTGGAGCCTCTGCCTGCGGACCTGGCCCAACTCTACCAGC





TCTGCCTG

TGGATTGAG

TCTACCAGCATC

ATCAGCTCAATCCAACCCTGCTCC





ZFP36
NM_003407
2609
CATTAACCCA
2610
CCCCCACCAT
2611
CAGGTCCCCAAG
2612
CATTAACCCACTCCCCTGACCTCACGCTGGGGCAGGTCCCCA





CTCCCCTGA

CATGAATACT

TGTGCAAGCTC

AGTGTGCAAGCTCAGTATTCATGATGGTGGGGG





ZMYND8
NM_183047
2613
GGTCTGGGCC
2614
TGCCCGTCTT
2615
CTTTTGCAGGCC
2616
GGTCTGGGCCAAACTGAAGGGGTTTCCATTCTGGCCTGCAAAA





AAACTGAAG

TATCCCTTAG

AGAATGGAAACC

GCTCTAAGGGATAAAGACGGGCA





ZNF3
NM_017715
2617
CGAAGGGACT
2618
GCAGGAGGTC
2619
AGGAGGTTCCAC
2620
CGAAGGGACTCTGCTCCAGTGAACTGGCGAGTGTGGAACCTC





CTGCTCCA

CTCAGAAGG

ACTCGCCAGTTC

CTGACACCTTCTGAGGACCTCCTGC





ZNF827
NM_178835
2621
TGCCTGAGGA
2622
GAGGTGGCGG
2623
CCCGCCTTCAGA
2624
TGCCTGAGGACCCTCTACCGCCCCCGCCTTCAGAGAAGAAAC





CCCTCTACC

AGTGACTTT

GAAGAAACCAGA

CAGAAAAAGTCACTCCGCCACCTC





ZWINT
NM_007057
2625
TAGAGGCCAT
2626
TCCGTTTCCT
2627
ACCAAGGCCCTG
2628
TAGAGGCCATCAAAATTGGCCTCACCAAGGCCCTGACTCAGAT





CAAAATTGGC

CTGGGCTT

ACTCAGATGGAG

GGAGGAAGCCCAGAGGAAACGGA




















TABLE B









SEQ





ID



microRNA
Sequence
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 the expression of RNA transcripts of genes in a human prostate cancer patient, comprising: obtaining a prostate tumor tissue sample from a human prostate cancer patient;extracting RNA from the tissue sample;reverse transcribing RNA transcripts of a group of genes comprising each of: BGN, COL1A1, SFRP4, FLNC, GSN, GSTM2, TPM2, AZGP1, KLK2, FAM13C, SRD5A2, and TPX2, and at least one reference gene, to produce cDNAs from the RNA transcripts, wherein a 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; andamplifying the cDNAs to produce amplicons from the cDNAs for determination of expression levels of the RNA transcripts.
  • 22. The method of claim 21, wherein the at least one reference gene consists of from 1 to 6 reference genes.
  • 23. 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.
  • 24. The method of claim 21, wherein the at least one reference gene is selected from the group consisting of AAMP, ARF1, ATP5E, CLTC, EEF1A1, GPS1, GPX1, and PGK1.
  • 25. The method of claim 21, wherein the tissue sample has a positive TMPRSS2 fusion status.
  • 26. The method of claim 21, wherein the tissue sample has a negative TMPRSS2 fusion status.
  • 27. The method of claim 21, wherein the patient has early-stage prostate cancer.
  • 28. The method of claim 21, wherein the tissue sample comprises prostate tumor tissue with the primary Gleason pattern for the patient's prostate tumor.
  • 29. The method of claim 21, wherein the tissue sample comprises prostate tumor tissue with the highest Gleason pattern for the patient's prostate tumor.
  • 30. The method of claim 21, wherein the tissue sample comprises non-tumor prostate tissue.
  • 31. 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. 14/887,605, filed Oct. 20, 2015, 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 (2)
Number Date Country
Parent 14887605 Oct 2015 US
Child 16282540 US
Parent 13190391 Jul 2011 US
Child 14887605 US