Method for using gene expression to determine prognosis of prostate cancer

Information

  • Patent Grant
  • 10260104
  • Patent Number
    10,260,104
  • Date Filed
    Tuesday, October 20, 2015
    8 years ago
  • Date Issued
    Tuesday, April 16, 2019
    5 years ago
Abstract
The present disclosure includes 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 the patient, and likelihood that the patient will have a recurrence of prostate cancer, or to classify the tumor by likelihood of clinical outcome or TMPRSS2 fusion status.
Description
TECHNICAL FIELD

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


INTRODUCTION

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


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


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


SUMMARY

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


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


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


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


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





BRIEF DESCRIPTION OF THE DRAWING


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





DEFINITIONS

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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


“Moderately stringent conditions” may be identified as described by Sambrook et al., Molecular Cloning: A Laboratory Manual, New York: Cold Spring Harbor Press, 1989, and include the use of washing solution and hybridization conditions (e.g., temperature, ionic strength and % SDS) less stringent that those described above. An example of moderately stringent conditions is overnight incubation at 37° C. in a solution comprising: 20% formamide, 5×SSC (150 mM NaCl, 15 mM trisodium citrate), 50 mM sodium phosphate (pH 7.6), 5×Denhardt's solution, 10% dextran sulfate, and 20 mg/ml denatured sheared salmon sperm DNA, followed by washing the filters in 1×SSC at about 37-500 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 MasterPure™ Complete DNA and RNA Purification Kit (EPICENTRE®, Madison, Wis.), and Paraffin Block RNA Isolation Kit (Ambion, Inc.). Total RNA from tissue samples can be isolated using RNA Stat-60 (Tel-Test). RNA prepared from tumor can be isolated, for example, by cesium chloride density gradient centrifugation.


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










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)










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


CDS 2


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


Official
Primary Pattern
Highest Pattern
Primary Pattern
Highest Pattern















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


















AKR1C3
1.304
0.022
1.312
0.013






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


AQP2
1.184
0.027
1.276
<.001






ASAP2


1.442
0.006






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


ATP5E
1.414
0.013
1.538
<.001






BAG5


1.263
0.044






BAX


1.332
0.026
1.327
0.012
1.438
0.002


BGN
1.947
<.001
2.061
<.001
1.339
0.017




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


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


BMPR1B
1.401
0.013


1.325
0.016




BRCA2






1.259
0.007


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


CADPS




1.387
0.009
1.294
0.027


CCNB1




1.296
0.016
1.376
0.002


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


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


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


CDC6
1.400
0.003
1.290
0.030
1.403
0.002
1.276
0.019


CDH7
1.403
0.003
1.413
0.002






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


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


CDKN3
1.384
<.001
1.255
0.024
1.285
0.003
1.216
0.028


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


CKS2
1.390
0.007
1.418
0.005
1.291
0.018




CLTC


1.368
0.045






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


COL1A2


1.462
0.001






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


COL4A1
1.490
0.002
1.613
<.001






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


CRISP3
1.425
0.001
1.467
<.001
1.242
0.045




CTHRC1
1.505
0.002
2.025
<.001
1.425
0.003
1.369
0.005


CTNND2




1.412
0.003




CXCR4
1.312
0.023
1.355
0.008






DDIT4
1.543
<.001
1.763
<.001






DYNLL1
1.290
0.039




1.201
0.004


EIF3H




1.428
0.012




ENY2
1.361
0.014


1.392
0.008
1.371
0.001


EZH2


1.311
0.010






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


FADD


1.292
0.018






FAM171B


1.285
0.036






FAP
1.455
0.004
1.560
0.001
1.298
0.022
1.274
0.038


FASN
1.263
0.035








FCGR3A


1.654
<.001
1.253
0.033
1.350
0.007


FGF5
1.219
0.030








GNPTAB
1.388
0.007
1.503
0.003
1.355
0.005
1.434
0.002


GPR68


1.361
0.008






GREM1
1.470
0.003
1.716
<.001
1.421
0.003
1.316
0.017


HDAC1




1.290
0.025




HDAC9


1.395
0.012






HRAS
1.424
0.006
1.447
0.020






HSD17B4
1.342
0.019
1.282
0.026
1.569
<.001
1.390
0.002


HSPA8
1.290
0.034








IGFBP3
1.333
0.022
1.442
0.003
1.253
0.040
1.323
0.005


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


JAG1
1.359
0.006
1.367
0.005
1.259
0.024




KCNN2
1.361
0.011
1.413
0.005
1.312
0.017
1.281
0.030


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


KIAA0196






1.249
0.037


KIF4A
1.212
0.016


1.149
0.040
1.278
0.003


KLK14
1.167
0.023




1.180
0.007


KPNA2


1.425
0.009
1.353
0.005
1.305
0.019


KRT75






1.164
0.028


LAMA3




1.327
0.011




LAMB1


1.347
0.019






LAMC1
1.555
0.001
1.310
0.030


1.349
0.014


LIMS1






1.275
0.022


LOX




1.358
0.003
1.410
<.001


LTBP2
1.396
0.009
1.656
<.001
1.278
0.022




LUM


1.315
0.021






MANF




1.660
<.001
1.323
0.011


MCM2




1.345
0.011
1.387
0.014


MCM6
1.307
0.023
1.352
0.008


1.244
0.039


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


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


MRPL13






1.260
0.025


MSH2


1.295
0.027






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


MYO6


1.301
0.033






NETO2
1.412
0.004
1.302
0.027
1.298
0.009




NFKB1




1.236
0.050




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


NPM1




1.287
0.036




NRIP3


1.219
0.031


1.218
0.018


NRP1


1.482
0.002


1.245
0.041


OLFML2B


1.362
0.015






OR51E1




1.531
<.001
1.488
0.003


PAK6


1.269
0.033






PATE1
1.308
<.001
1.332
<.001
1.164
0.044




PCNA






1.278
0.020


PEX10
1.436
0.005
1.393
0.009






PGD
1.298
0.048


1.579
<.001




PGK1


1.274
0.023


1.262
0.009


PLA2G7




1.315
0.011
1.346
0.005


PLAU




1.319
0.010




PLK1
1.309
0.021
1.563
<.001
1.410
0.002
1.372
0.003


PLOD2


1.284
0.019
1.272
0.014
1.332
0.005


POSTN
1.599
<.001
1.514
0.002
1.391
0.005




PPP3CA




1.402
0.007
1.316
0.018


PSMD13
1.278
0.040
1.297
0.033
1.279
0.017
1.373
0.004


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


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


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


RAF1




1.503
0.002




RALA
1.521
0.004
1.403
0.007
1.563
<.001
1.229
0.040


RALBP1




1.277
0.033




RGS7
1.154
0.015
1.266
0.010






RRM1
1.570
0.001
1.602
<.001






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


SAT1
1.482
0.016
1.403
0.030






SDC1




1.340
0.018
1.396
0.018


SEC14L1


1.260
0.048


1.360
0.002


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


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


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


SKIL




1.327
0.008




SLC25A21




1.398
0.001
1.285
0.018


SOX4




1.286
0.020
1.280
0.030


SPARC
1.539
<.001
1.842
<.001


1.269
0.026


SPP1


1.322
0.022






SQLE


1.359
0.020
1.270
0.036




STMN1
1.402
0.007
1.446
0.005
1.279
0.031




SULF1


1.587
<.001






TAF2






1.273
0.027


TFDP1


1.328
0.021
1.400
0.005
1.416
0.001


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


THY1
1.362
0.020
1.662
<.001






TK1


1.251
0.011
1.377
<.001
1.401
<.001


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


TPD52
1.324
0.011


1.366
0.002
1.351
0.005


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


UAP1




1.244
0.044




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


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


UGT2B15


1.295
0.001


1.275
0.002


UGT2B17






1.294
0.025


UHRF1
1.454
<.001
1.531
<.001
1.257
0.029




VCPIP1
1.390
0.009
1.414
0.004
1.294
0.021
1.283
0.021


WNT5A


1.274
0.038
1.298
0.020




XIAP




1.464
0.006




ZMYND8


1.277
0.048






ZWINT
1.259
0.047
















TABLE 4B







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


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


positively associated with good prognosis)












cRFI
cRFI
bRFI
bRFI


Official
Primary Pattern
Highest Pattern
Primary Pattern
Highest Pattern















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


















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


ABCA5
0.755
<.001
0.695
<.001


0.800
0.006


ABCB1
0.777
0.026








ABCG2
0.788
0.033
0.784
0.040
0.803
0.018
0.750
0.004


ABHD2


0.734
0.011






ACE


0.782
0.048






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


ADH5
0.625
<.001
0.637
<.001
0.753
0.026




AKAP1
0.764
0.006
0.800
0.005
0.837
0.046




AKR1C1
0.773
0.033


0.802
0.032




AKT1


0.714
0.005






AKT3
0.811
0.015
0.809
0.021






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


AMPD3




0.793
0.024




ANPEP
0.584
<.001
0.493
<.001






ANXA2
0.753
0.013
0.781
0.036
0.762
0.008
0.795
0.032


APRT


0.758
0.026
0.780
0.044
0.746
0.008


ATXN1
0.673
0.001
0.776
0.029
0.809
0.031
0.812
0.043


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


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


BAD


0.765
0.023






BCL2
0.788
0.033
0.778
0.036






BDKRB1
0.728
0.039








BIK


0.712
0.005






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


BTG3




0.847
0.034




BTRC
0.688
0.001
0.713
0.003






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


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


CASP1
0.769
0.014
0.799
0.028
0.799
0.010
0.815
0.018


CAV1
0.736
0.011
0.711
0.005
0.675
<.001
0.743
0.006


CAV2


0.636
0.010
0.648
0.012
0.685
0.012


CCL2
0.759
0.029
0.764
0.024






CCNH
0.689
<.001
0.700
<.001






CD164
0.664
<.001
0.651
<.001






CD1A




0.687
0.004




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


CD82
0.771
0.009
0.748
0.004






CDC25B
0.755
0.006


0.817
0.025




CDK14
0.845
0.043








CDK2






0.819
0.032


CDK3
0.733
0.005


0.772
0.006
0.838
0.017


CDKN1A


0.766
0.041






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


CHN1
0.788
0.036








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


CSF1
0.626
<.001
0.709
0.003






CSK




0.837
0.029




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


Official
Primary Pattern
Highest Pattern
Primary Pattern
Highest Pattern















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


















AKR1C3
1.315
0.018
1.283
0.024






ALOX12






1.198
0.024


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


AQP2
1.209
<.001
1.302
<.001






ASAP2


1.582
<.001
1.333
0.011
1.307
0.019


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


ATP5E
1.309
0.042
1.369
0.012






BAG5


1.291
0.044






BAX




1.298
0.025
1.420
0.004


BGN
1.746
<.001
1.755
<.001






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


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


BRCA2






1.184
0.037


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


CACNA1D


1.313
0.029






CADPS




1.358
0.007
1.267
0.022


CASP3




1.251
0.037




CCNB1




1.261
0.033
1.318
0.005


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


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


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


CDC6
1.340
0.011
1.265
0.046
1.367
0.002
1.272
0.025


CDH7
1.402
0.003
1.409
0.002






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


CDKN2C
1.411
<.001
1.604
<.001
1.220
0.033




CDKN3
1.296
0.004


1.226
0.015




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


CKS2
1.419
0.008
1.374
0.022
1.380
0.004




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


COL1A2


1.373
0.010






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


COL4A1
1.475
0.002
1.513
0.002






COL8A1
1.506
0.001
1.691
<.001






CRISP3
1.406
0.004
1.471
<.001






CTHRC1
1.426
0.009
1.793
<.001
1.311
0.019




CTNND2




1.462
<.001




DDIT4
1.478
0.003
1.783
<.001


1.236
0.039


DYNLL1
1.431
0.002




1.193
0.004


EIF3H




1.372
0.027




ENY2




1.325
0.023
1.270
0.017


ERG
1.303
0.041








EZH2


1.254
0.049






F2R
1.540
0.002
1.448
0.006
1.286
0.023




FADD
1.235
0.041
1.404
<.001






FAP
1.386
0.015
1.440
0.008
1.253
0.048




FASN
1.303
0.028








FCGR3A


1.439
0.011


1.262
0.045


FGF5
1.289
0.006








GNPTAB
1.290
0.033
1.369
0.022
1.285
0.018
1.355
0.008


GPR68


1.396
0.005






GREM1
1.341
0.022
1.502
0.003
1.366
0.006




HDAC1




1.329
0.016




HDAC9


1.378
0.012






HRAS
1.465
0.006








HSD17B4




1.442
<.001
1.245
0.028


IGFBP3


1.366
0.019


1.302
0.011


INHBA
2.000
<.001
2.336
<.001


1.486
0.002


JAG1
1.251
0.039








KCNN2
1.347
0.020
1.524
<.001
1.312
0.023
1.346
0.011


KHDRBS3


1.500
0.001
1.426
0.001
1.267
0.032


KIAA0196






1.272
0.028


KIF4A
1.199
0.022




1.262
0.004


KPNA2




1.252
0.016




LAMA3




1.332
0.004
1.356
0.010


LAMB1


1.317
0.028






LAMC1
1.516
0.003
1.302
0.040


1.397
0.007


LIMS1






1.261
0.027


LOX




1.265
0.016
1.372
0.001


LTBP2


1.477
0.002






LUM


1.321
0.020






MANF




1.647
<.001
1.284
0.027


MCM2




1.372
0.003
1.302
0.032


MCM3


1.269
0.047






MCM6


1.276
0.033


1.245
0.037


MELK


1.294
0.005
1.394
<.001




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



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)










Primary Pattern
Highest Pattern











Official Symbol
HR
p-value
HR
p-value














ANLN
1.42
0.012
1.36
0.004


AQP2
1.25
0.033




ASPN
2.48
<.001
1.65
<.001


BGN
2.04
<.001
1.45
0.007


BIRC5
1.59
<.001
1.37
0.005


BMP6
1.95
<.001
1.43
0.012


BMPR1B
1.93
0.002




BUB1
1.51
<.001
1.35
<.001


CCNE2
1.48
0.007




CD276
1.93
<.001
1.79
<.001


CDC20
1.49
0.004
1.47
<.001


CDC6
1.52
0.009
1.34
0.022


CDKN2B
1.54
0.008
1.55
0.003


CDKN2C
1.55
0.003
1.57
<.001


CDKN3
1.34
0.026




CENPF
1.63
0.002
1.33
0.018


CKS2
1.50
0.026
1.43
0.009


CLTC


1.46
0.014


COL1A1
1.98
<.001
1.50
0.002


COL3A1
2.03
<.001
1.42
0.007


COL4A1
1.81
0.002




COL8A1
1.63
0.004
1.60
0.001


CRISP3


1.31
0.016


CTHRC1
1.67
0.006
1.48
0.005


DDIT4
1.49
0.037




ENY2


1.29
0.039


EZH2


1.35
0.016


F2R
1.46
0.034
1.46
0.007


FAP
1.66
0.006
1.38
0.012


FGF5


1.46
0.001


GNPTAB
1.49
0.013




HSD17B4
1.34
0.039
1.44
0.002


INHBA
2.92
<.001
2.19
<.001


JAG1
1.38
0.042




KCNN2
1.71
0.002
1.73
<.001


KHDRBS3


1.46
0.015


KLK14
1.28
0.034




KPNA2
1.63
0.016




LAMC1
1.41
0.044




LOX


1.29
0.036


LTBP2
1.57
0.017




MELK
1.38
0.029




MMP11
1.69
0.002
1.42
0.004


MYBL2
1.78
<.001
1.49
<.001


NETO2
2.01
<.001
1.43
0.007


NME1


1.38
0.017


PATE1
1.43
<.001
1.24
0.005


PEX10
1.46
0.030




PGD
1.77
0.002




POSTN
1.49
0.037
1.34
0.026


PPFIA3
1.51
0.012




PPP3CA
1.46
0.033
1.34
0.020


PTK6
1.69
<.001
1.56
<.001


PTTG1
1.35
0.028




RAD51
1.32
0.048




RALBP1


1.29
0.042


RGS7
1.18
0.012
1.32
0.009


RRM1
1.57
0.016
1.32
0.041


RRM2
1.30
0.039




SAT1
1.61
0.007




SESN3
1.76
<.001
1.36
0.020


SFRP4
1.55
0.016
1.48
0.002


SHMT2
2.23
<.001
1.59
<.001


SPARC
1.54
0.014




SQLE
1.86
0.003




STMN1
2.14
<.001




THBS2
1.79
<.001
1.43
0.009


TK1
1.30
0.026




TOP2A
2.03
<.001
1.47
0.003


TPD52
1.63
0.003




TPX2
2.11
<.001
1.63
<.001


TRAP1
1.46
0.023




UBE2C
1.57
<.001
1.58
<.001


UBE2G1
1.56
0.008




UBE2T
1.75
<.001




UGT2B15
1.31
0.036
1.33
0.004


UHRF1
1.46
0.007




UTP23
1.52
0.017


















TABLE 7B







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


fusion negative in the primary Gleason pattern or highest Gleason pattern


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


with good prognosis)










Primary Pattern
Highest Pattern











Official Symbol
HR
p-value
HR
p-value














AAMP
0.56
<.001
0.65
0.001


ABCA5
0.64
<.001
0.71
<.001


ABCB1
0.62
0.004




ABCC3


0.74
0.031


ABCG2


0.78
0.050


ABHD2
0.71
0.035




ACOX2
0.54
<.001
0.71
0.007


ADH5
0.49
<.001
0.61
<.001


AKAP1
0.77
0.031
0.76
0.013


AKR1C1
0.65
0.006
0.78
0.044


AKT1


0.72
0.020


AKT3
0.75
<.001




ALDH1A2
0.53
<.001
0.60
<.001


AMPD3
0.62
<.001
0.78
0.028


ANPEP
0.54
<.001
0.61
<.001


ANXA2
0.63
0.008
0.74
0.016


ARHGAP29
0.67
0.005
0.77
0.016


ARHGDIB
0.64
0.013




ATP5J
0.57
0.050




ATXN1
0.61
0.004
0.77
0.043


AXIN2
0.51
<.001
0.62
<.001


AZGP1
0.61
<.001
0.64
<.001


BCL2
0.64
0.004
0.75
0.029


BIN1
0.52
<.001
0.74
0.010


BTG3
0.75
0.032
0.75
0.010


BTRC
0.69
0.011




C7
0.51
<.001
0.67
<.001


CADM1
0.49
<.001
0.76
0.034


CASP1
0.71
0.010
0.74
0.007


CAV1


0.73
0.015


CCL5
0.67
0.018
0.67
0.003


CCNH
0.63
<.001
0.75
0.004


CCR1


0.77
0.032


CD164
0.52
<.001
0.63
<.001


CD44
0.53
<.001
0.74
0.014


CDH10
0.69
0.040




CDH18
0.40
0.011




CDK14
0.75
0.013




CDK2


0.81
0.031


CDK3
0.73
0.022




CDKN1A
0.68
0.038




CDKN1C
0.62
0.003
0.72
0.005


COL6A1
0.54
<.001
0.70
0.004


COL6A3
0.64
0.004




CSF1
0.56
<.001
0.78
0.047


CSRP1
0.40
<.001
0.66
0.002


CTGF
0.66
0.015
0.74
0.027


CTNNB1
0.69
0.043




CTSB
0.60
0.002
0.71
0.011


CTSS
0.67
0.013




CXCL12
0.56
<.001
0.77
0.026


CYP3A5
0.43
<.001
0.63
<.001


CYR61
0.43
<.001
0.58
<.001


DAG1
0.72
0.012




DARC
0.66
0.016




DDR2
0.65
0.007




DES
0.52
<.001
0.74
0.018


DHRS9
0.54
0.007




DICER1
0.70
0.044




DLC1


0.75
0.021


DLGAP1
0.55
<.001
0.72
0.005


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


PRIMAL
0.51
<.001
0.68
0.004


PRKCA
0.55
<.001
0.74
0.009


PRKCB
0.55
<.001




PROM1


0.67
0.042


PROS 1
0.73
0.036




PTCH1
0.69
0.024
0.72
0.010


PTEN
0.54
<.001
0.64
<.001


PTGS 2
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)










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


INHB A
2.03
<.001
2.64
<.001


JAG1
1.41
0.027
1.50
0.008


KCTD12


1.51
0.017


KHDRBS3
1.48
0.029
1.54
0.014


KPNA2


1.46
0.050


LAMA3
1.35
0.040




LAMC1
1.77
0.012




LTBP2


1.82
<.001


LUM
1.51
0.021
1.53
0.009


MELK
1.38
0.020
1.49
0.001


MKI67


1.37
0.014


MMP11
1.73
<.001
1.69
<.001


MRPL13


1.30
0.046


MYBL2
1.56
<.001
1.72
<.001


MYLK3


1.17
0.007


NOX4
1.58
0.005
1.96
<.001


NRIP3


1.30
0.040


NRP1


1.53
0.021


OLFML2B


1.54
0.024


OSM
1.43
0.018




PATE1
1.20
<.001
1.33
<.001


PCNA


1.64
0.003


PEX10
1.41
0.041
1.64
0.003


PIK3CA
1.38
0.037




PLK1
1.52
0.009
1.67
0.002


PLOD2


1.65
0.002


POSTN
1.79
<.001
2.06
<.001


PTK6
1.67
0.002
2.38
<.001


PTTG1
1.56
0.002
1.54
0.003


RAD21
1.61
0.036
1.53
0.005


RAD51


1.33
0.009


RALA
1.95
0.004
1.60
0.007


REG4


1.43
0.042


ROBO2
1.46
0.024




RRM1


1.44
0.033


RRM2
1.50
0.003
1.48
<.001


SAT1
1.42
0.009
1.43
0.012


SEC14L1


1.64
0.002


SFRP4
2.07
<.001
2.40
<.001


SHMT2
1.52
0.030
1.60
0.001


SLC44A1


1.42
0.039


SPARC
1.93
<.001
2.21
<.001


SULF1
1.63
0.006
2.04
<.001


THBS2
1.95
<.001
2.26
<.001


THY1
1.69
0.016
1.95
0.002


TK1


1.43
0.003


TOP2A
1.57
0.002
2.11
<.001


TPX2
1.84
<.001
2.27
<.001


UBE2C
1.41
0.011
1.44
0.006


UBE2T
1.63
0.001




UHRF1
1.51
0.007
1.69
<.001


WISP1
1.47
0.045




WNT5A
1.35
0.027
1.63
0.001


ZWINT
1.36
0.045
















TABLE 8B







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


fusion positive in the primary Gleason pattern or highest Gleason pattern


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


with good prognosis)










Primary Pattern
Highest Pattern











Official Symbol
HR
p-value
HR
p-value














AAMP
0.57
0.007
0.58
<.001


ABCA5


0.80
0.044


ACE
0.65
0.023
0.55
<.001


ACOX2


0.55
<.001


ADH5


0.68
0.022


AKAP1


0.81
0.043


ALDH1A2
0.72
0.036
0.43
<.001


ANPEP
0.66
0.022
0.46
<.001


APRT


0.73
0.040


AXIN2


0.60
<.001


AZGP1
0.57
<.001
0.65
<.001


BCL2


0.69
0.035


BIK
0.71
0.045




BIN1
0.71
0.004
0.71
0.009


BTRC
0.66
0.003
0.58
<.001


C7


0.64
0.006


CADM1
0.61
<.001
0.47
<.001


CCL2


0.73
0.042


CCNH
0.69
0.022




CD44
0.56
<.001
0.58
<.001


CD82


0.72
0.033


CDC25B
0.74
0.028




CDH1
0.75
0.030
0.72
0.010


CDH19


0.56
0.015


CDK3


0.78
0.045


CDKN1C
0.74
0.045
0.70
0.014


CSF1


0.72
0.037


CTSB


0.69
0.048


CTSL2


0.58
0.005


CYP3A5
0.51
<.001
0.30
<.001


DHX9
0.89
0.006
0.87
0.012


DLC1


0.64
0.023


DLGAP1
0.69
0.010
0.49
<.001


DPP4
0.64
<.001
0.56
<.001


DPT


0.63
0.003


EGR1


0.69
0.035


EGR3


0.68
0.025


EIF2S3
0.70
0.021




EIF5
0.71
0.030




ELK4
0.71
0.041
0.60
0.003


EPHA2
0.72
0.036
0.66
0.011


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









Official Symbol
p-value
Odds Ratio












ABCC8
<.001
1.86


ALDH18A1
0.005
1.49


ALKBH3
0.043
1.30


ALOX5
<.001
1.66


AMPD3
<.001
3.92


APEX1
<.001
2.00


ARHGDIB
<.001
1.87


ASAP2
0.019
1.48


ATXN1
0.013
1.41


BMPR1B
<.001
2.37


CACNA1D
<.001
9.01


CADPS
0.015
1.39


CD276
0.003
2.25


CDH1
0.016
1.37


CDH7
<.001
2.22


CDK7
0.025
1.43


COL9A2
<.001
2.58


CRISP3
<.001
2.60


CTNND1
0.033
1.48


ECE1
<.001
2.22


EIF5
0.023
1.34


EPHB4
0.005
1.51


ERG
<.001
14.5


FAM171B
0.047
1.32


FAM73A
0.008
1.45


FASN
0.004
1.50


GNPTAB
<.001
1.60


GPS1
0.006
1.45


GRB7
0.023
1.38


HDAC1
<.001
4.95


HGD
<.001
1.64


HIP1
<.001
1.90


HNF1B
<.001
3.55


HSPA8
0.041
1.32


IGF1R
0.001
1.73


ILF3
<.001
1.91


IMMT
0.025
1.36


ITPR1
<.001
2.72


ITPR3
<.001
5.91


JAG1
0.007
1.42


KCNN2
<.001
2.80


KHDRBS3
<.001
2.63


KIAA0247
0.019
1.38


KLK11
<.001
1.98


LAMC1
0.008
1.56


LAMC2
<.001
3.30


LOX
0.009
1.41


LRP1
0.044
1.30


MAP3K5
<.001
2.06


MAP7
<.001
2.74


MSH2
0.005
1.59


MSH3
0.006
1.45


MUC1
0.012
1.42


MYO6
<.001
3.79


NCOR2
0.001
1.62


NDRG1
<.001
6.77


NETO2
<.001
2.63


ODC1
<.001
1.98


OR51E1
<.001
2.24


PDE9A
<.001
2.21


PEX10
<.001
3.41


PGK1
0.022
1.33


PLA2G7
<.001
5.51


PPP3CA
0.047
1.38


PSCA
0.013
1.43


PSMD13
0.004
1.51


PTCH1
0.022
1.38


PTK2
0.014
1.38


PTK6
<.001
2.29


PTK7
<.001
2.45


PTPRK
<.001
1.80


RAB30
0.001
1.60


REG4
0.018
1.58


RELA
0.001
1.62


RFX1
0.020
1.43


RGS10
<.001
1.71


SCUBE2
0.009
1.48


SEPT9
<.001
3.91


SH3RF2
0.004
1.48


SH3YL1
<.001
1.87


SHH
<.001
2.45


SIM2
<.001
1.74


SIPA1L1
0.021
1.35


SLC22A3
<.001
1.63


SLC44A1
<.001
1.65


SPINT1
0.017
1.39


TFDP1
0.005
1.75


TMPRSS2ERGA
0.002
14E5


TMPRSS2ERGB
<.001
1.97


TRIM14
<.001
1.65


TSTA3
0.018
1.38


UAP1
0.046
1.39


UBE2G1
0.001
1.66


UGDH
<.001
2.22


XRCC5
<.001
1.66


ZMYND8
<.001
2.19
















TABLE 9B







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


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


expression is negatively associated with TMPRSS fusion positivity)









Official Symbol
p-value
Odds Ratio












ABCC4
0.045
0.77


ABHD2
<.001
0.38


ACTR2
0.027
0.73


ADAMTS1
0.024
0.58


ADH5
<.001
0.58


AGTR2
0.016
0.64


AKAP1
0.013
0.70


AKT2
0.015
0.71


ALCAM
<.001
0.45


ALDH1A2
0.004
0.70


ANPEP
<.001
0.43


ANXA2
0.010
0.71


APC
0.036
0.73


APOC1
0.002
0.56


APOE
<.001
0.44


ARF1
0.041
0.77


ATM
0.036
0.74


AURKB
<.001
0.62


AZGP1
<.001
0.54


BBC3
0.030
0.74


BCL2
0.012
0.70


BIN1
0.021
0.74


BTG1
0.004
0.67


BTG3
0.003
0.63


C7
0.023
0.74


CADM1
0.007
0.69


CASP1
0.011
0.70


CAV1
0.011
0.71


CCND1
0.019
0.72


CCR1
0.022
0.73


CD44
<.001
0.57


CD68
<.001
0.54


CD82
0.002
0.66


CDH5
0.007
0.66


CDKN1A
<.001
0.60


CDKN2B
<.001
0.54


CDKN2C
0.012
0.72


CDKN3
0.037
0.77


CHN1
0.038
0.75


CKS2
<.001
0.48


COL11A1
0.017
0.72


COL1A1
<.001
0.59


COL1A2
0.001
0.62


COL3A1
0.027
0.73


COL4A1
0.043
0.76


COL5A1
0.039
0.74


COL5A2
0.026
0.73


COL6A1
0.008
0.66


COL6A3
<.001
0.59


COL8A1
0.022
0.74


CSF1
0.011
0.70


CTNNB1
0.021
0.69


CTSB
<.001
0.62


CTSD
0.036
0.68


CTSK
0.007
0.70


CTSS
0.002
0.64


CXCL12
<.001
0.48


CXCR4
0.005
0.68


CXCR7
0.046
0.76


CYR61
0.004
0.65


DAP
0.002
0.64


DARC
0.021
0.73


DDR2
0.021
0.73


DHRS9
<.001
0.52


DIAPH1
<.001
0.56


DICER1
0.029
0.75


DLC1
0.013
0.72


DLGAP1
<.001
0.60


DLL4
<.001
0.57


DPT
0.006
0.68


DUSP1
0.012
0.68


DUSP6
0.001
0.62


DVL1
0.037
0.75


EFNB2
<.001
0.32


EGR1
0.003
0.65


ELK4
<.001
0.60


ERBB2
<.001
0.61


ERBB3
0.045
0.76


ESR2
0.010
0.70


ETV1
0.042
0.74


FABP5
<.001
0.21


FAM13C
0.006
0.67


FCGR3A
0.018
0.72


FGF17
0.009
0.71


FGF6
0.011
0.70


FGF7
0.003
0.63


FN1
0.006
0.69


FOS
0.035
0.74


FOXP3
0.010
0.71


GABRG2
0.029
0.74


GADD45B
0.003
0.63


GDF15
<.001
0.54


GPM6B
0.004
0.67


GPNMB
0.001
0.62


GSN
0.009
0.69


HLA-G
0.050
0.74


HLF
0.018
0.74


HPS1
<.001
0.48


HSD17B3
0.003
0.60


HSD17B4
<.001
0.56


HSPB1
<.001
0.38


HSPB2
0.002
0.62


IFI30
0.049
0.75


IFNG
0.006
0.64


IGF1
0.016
0.73


IGF2
0.001
0.57


IGFBP2
<.001
0.51


IGFBP3
<.001
0.59


IGFBP6
<.001
0.57


IL10
<.001
0.62


IL17A
0.012
0.63


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)










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)










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)









Official Symbol
HR
p-value












AKR1C3
1.476
0.016


ANLN
1.517
0.006


APOC1
1.285
0.016


APOE
1.490
0.024


ASPN
3.055
<.001


ATP5E
1.788
0.012


AURKB
1.439
0.008


BGN
2.640
<.001


BIRC5
1.611
<.001


BMP6
1.490
0.021


BRCA1
1.418
0.036


CCNB1
1.497
0.021


CD276
1.668
0.005


CDC20
1.730
<.001


CDH11
1.565
0.017


CDH7
1.553
0.007


CDKN2B
1.751
0.003


CDKN2C
1.993
0.013


CDKN3
1.404
0.008


CENPF
2.031
<.001


CHAF1A
1.376
0.011


CKS2
1.499
0.031


COL1A1
2.574
<.001


COL1A2
1.607
0.011


COL3A1
2.382
<.001


COL4A1
1.970
<.001


COL5A2
1.938
0.002


COL8A1
2.245
<.001


CTHRC1
2.085
<.001


CXCR4
1.783
0.007


DDIT4
1.535
0.030


DYNLL1
1.719
0.001


F2R
2.169
<.001


FAM171B
1.430
0.044


FAP
1.993
0.002


FCGR3A
2.099
<.001


FN1
1.537
0.024


GPR68
1.520
0.018


GREM1
1.942
<.001


IFI30
1.482
0.048


IGFBP3
1.513
0.027


INHBA
3.060
<.001


KIF4A
1.355
0.001


KLK14
1.187
0.004


LAPTM5
1.613
0.006


LTBP2
2.018
<.001


MMP11
1.869
<.001


MYBL2
1.737
0.013


NEK2
1.445
0.028


NOX4
2.049
<.001


OLFML2B
1.497
0.023


PLK1
1.603
0.006


POSTN
2.585
<.001


PPFIA3
1.502
0.012


PTK6
1.527
0.009


PTTG1
1.382
0.029


RAD51
1.304
0.031


RGS7
1.251
<.001


RRM2
1.515
<.001


SAT1
1.607
0.004


SDC1
1.710
0.007


SESN3
1.399
0.045


SFRP4
2.384
<.001


SHMT2
1.949
0.003


SPARC
2.249
<.001


STMN1
1.748
0.021


SULF1
1.803
0.004


THBS2
2.576
<.001


THY1
1.908
0.001


TK1
1.394
0.004


TOP2A
2.119
<.001


TPX2
2.074
0.042


UBE2C
1.598
<.001


UGT2B15
1.363
0.016


UHRF1
1.642
0.001


ZWINT
1.570
0.010
















TABLE 12B







Genes significantly (p < 0.05) associated with prostate cancer specific


survival (PCSS) in the Primary Gleason Pattern HR < 1.0 (Increased


expression is positively associated with good prognosis)









Official Symbol
HR
p-value












AAMP
0.649
0.040


ABCA5
0.777
0.015


ABCG2
0.715
0.037


ACOX2
0.673
0.016


ADH5
0.522
<.001


ALDH1A2
0.561
<.001


AMACR
0.693
0.029


AMPD3
0.750
0.049


ANPEP
0.531
<.001


ATXN1
0.640
0.011


AXIN2
0.657
0.002


AZGP1
0.617
<.001


BDKRB1
0.553
0.032


BIN1
0.658
<.001


BTRC
0.716
0.011


C7
0.531
<.001


CADM1
0.646
0.015


CASP7
0.538
0.029


CCNH
0.674
0.001


CD164
0.606
<.001


CD44
0.687
0.016


CDK3
0.733
0.039


CHN1
0.653
0.014


COL6A1
0.681
0.015


CSF1
0.675
0.019


CSRP1
0.711
0.007


CXCL12
0.650
0.015


CYP3A5
0.507
<.001


CYR61
0.569
0.007


DLGAP1
0.654
0.004


DNM3
0.692
0.010


DPP4
0.544
<.001


DPT
0.543
<.001


DUSP1
0.660
0.050


DUSP6
0.699
0.033


EGR1
0.490
<.001


EGR3
0.561
<.001


EIF5
0.720
0.035


ERBB3
0.739
0.042


FAAH
0.636
0.010


FAM107A
0.541
<.001


FAM13C
0.526
<.001


FAS
0.689
0.030


FGF10
0.657
0.024


FKBP5
0.699
0.040


FLNC
0.742
0.036


FOS
0.556
0.005


FOXQ1
0.666
0.007


GADD45B
0.554
0.002


GDF15
0.659
0.009


GHR
0.683
0.027


GPM6B
0.666
0.005


GSN
0.646
0.006


GSTM1
0.672
0.006


GSTM2
0.514
<.001


HGD
0.771
0.039


HIRIP3
0.730
0.013


HK1
0.778
0.048


HLF
0.581
<.001


HNF1B
0.643
0.013


HSD17B10
0.742
0.029


IER3
0.717
0.049


IGF1
0.612
<.001


IGFBP6
0.578
0.003


IL2
0.528
0.010


IL6ST
0.574
<.001


IL8
0.540
0.001


ING5
0.688
0.015


ITGA6
0.710
0.005


ITGA7
0.676
0.033


JUN
0.506
0.001


KIT
0.628
0.047


KLK1
0.523
0.002


KLK2
0.581
<.001


KLK3
0.676
<.001


KRT15
0.684
0.005


KRT18
0.536
<.001


KRT5
0.673
0.004


KRT8
0.613
0.006


LAMB3
0.740
0.027


LGALS3
0.678
0.007


MGST1
0.640
0.002


MPPED2
0.629
<.001


MTSS1
0.705
0.041


MYBPC1
0.534
<.001


NCAPD3
0.519
<.001


NFAT5
0.536
<.001


NRG1
0.467
0.007


OLFML3
0.646
0.001


OMD
0.630
0.006


OR51E2
0.762
0.017


PAGE4
0.518
<.001


PCA3
0.581
<.001


PGF
0.705
0.038


PPAP2B
0.568
<.001


PPP1R12A
0.694
0.017


PRIMA1
0.678
0.014


PRKCA
0.632
0.001


PRKCB
0.692
0.028


PROM1
0.393
0.017


PTEN
0.689
0.002


PTGS2
0.611
0.004


PTH1R
0.629
0.031


RAB27A
0.721
0.046


RND3
0.678
0.029


RNF114
0.714
0.035


SDHC
0.590
<.001


SERPINA3
0.710
0.050


SH3RF2
0.570
0.005


SLC22A3
0.517
<.001


SMAD4
0.528
<.001


SMO
0.751
0.026


SRC
0.667
0.004


SRD5A2
0.488
<.001


STAT5B
0.700
0.040


SVIL
0.694
0.024


TFF3
0.701
0.045


TGFB1I1
0.670
0.029


TGFB2
0.646
0.010


TNFRSF10B
0.685
0.014


TNFSF10
0.532
<.001


TPM2
0.623
0.005


TRO
0.767
0.049


TUBB2A
0.613
0.003


VEGFB
0.780
0.034


ZFP36
0.576
0.001


ZNF827
0.644
0.014









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


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









TABLE 13A







Genes significantly (p < 0.05) associated with upgrading/upstaging


in the Primary Gleason Pattern (PGP) and Highest Gleason Pattern


(HGP) OR > 1.0 (Increased expression is positively associated


with higher risk of upgrading/upstaging (poor prognosis))










PGP
HGP











Gene
OR
p-value
OR
p-value














ALCAM
1.52
0.0179
1.50
0.0184


ANLN
1.36
0.0451
.
.


APOE
1.42
0.0278
1.50
0.0140


ASPN
1.60
0.0027
2.06
0.0001


AURKA
1.47
0.0108
.
.


AURKB
.
.
1.52
0.0070


BAX
.
.
1.48
0.0095


BGN
1.58
0.0095
1.73
0.0034


BIRC5
1.38
0.0415
.
.


BMP6
1.51
0.0091
1.59
0.0071


BUB1
1.38
0.0471
1.59
0.0068


CACNA1D
1.36
0.0474
1.52
0.0078


CASP7
.
.
1.32
0.0450


CCNE2
1.54
0.0042
.
.


CD276
.
.
1.44
0.0265


CDC20
1.35
0.0445
1.39
0.0225


CDKN2B
.
.
1.36
0.0415


CENPF
1.43
0.0172
1.48
0.0102


CLTC
1.59
0.0031
1.57
0.0038


COL1A1
1.58
0.0045
1.75
0.0008


COL3A1
1.45
0.0143
1.47
0.0131


COL8A1
1.40
0.0292
1.43
0.0258


CRISP3
.
.
1.40
0.0256


CTHRC1
.
.
1.56
0.0092


DBN1
1.43
0.0323
1.45
0.0163


DIAPH1
1.51
0.0088
1.58
0.0025


DICER1
.
.
1.40
0.0293


DIO2
.
.
1.49
0.0097


DVL1
.
.
1.53
0.0160


F2R
1.46
0.0346
1.63
0.0024


FAP
1.47
0.0136
1.74
0.0005


FCGR3A
.
.
1.42
0.0221


HPN
.
.
1.36
0.0468


HSD17B4
.
.
1.47
0.0151


HSPA8
1.65
0.0060
1.58
0.0074


IL11
1.50
0.0100
1.48
0.0113


IL1B
1.41
0.0359
.
.


INHBA
1.56
0.0064
1.71
0.0042


KHDRBS3
1.43
0.0219
1.59
0.0045


KIF4A
.
.
1.50
0.0209


KPNA2
1.40
0.0366
.
.


KRT2
.
.
1.37
0.0456


KRT75
.
.
1.44
0.0389


MANF
.
.
1.39
0.0429


MELK
1.74
0.0016
.
.


MKI67
1.35
0.0408
.
.


MMP11
.
.
1.56
0.0057


NOX4
1.49
0.0105
1.49
0.0138


PLAUR
1.44
0.0185
.
.


PLK1
.
.
1.41
0.0246


PTK6
.
.
1.36
0.0391


RAD51
.
.
1.39
0.0300


RAF1
.
.
1.58
0.0036


RRM2
1.57
0.0080
.
.


SESN3
1.33
0.0465
.
.


SFRP4
2.33
<0.0001
2.51
0.0015


SKIL
1.44
0.0288
1.40
0.0368


SOX4
1.50
0.0087
1.59
0.0022


SPINK1
1.52
0.0058
.
.


SPP1
.
.
1.42
0.0224


THBS2
.
.
1.36
0.0461


TK1
.
.
1.38
0.0283


TOP2A
1.85
0.0001
1.66
0.0011


TPD52
1.78
0.0003
1.64
0.0041


TPX2
1.70
0.0010
.
.


UBE2G1
1.38
0.0491
.
.


UBE2T
1.37
0.0425
1.46
0.0162


UHRF1
.
.
1.43
0.0164


VCPIP1
.
.
1.37
0.0458
















TABLE 13B







Genes significantly (p < 0.05) associated with upgrading/upstaging


in the Primary Gleason Pattern (PGP) and Highest Gleason Pattern (HGP)


OR < 1.0 (Increased expression is negatively associated with higher


risk of upgrading/upstaging (good prognosis))










PGP
HGP











Gene
OR
p-value
OR
p-value














ABCC3
.
.
0.70
0.0216


ABCC8
0.66
0.0121
.
.


ABCG2
0.67
0.0208
0.61
0.0071


ACE
.
.
0.73
0.0442


ACOX2
0.46
0.0000
0.49
0.0001


ADH5
0.69
0.0284
0.59
0.0047


AIG1
.
.
0.60
0.0045


AKR1C1
.
.
0.66
0.0095


ALDH1A2
0.36
<0.0001
0.36
<0.0001


ALKBH3
0.70
0.0281
0.61
0.0056


ANPEP
.
.
0.68
0.0109


ANXA2
0.73
0.0411
0.66
0.0080


APC
.
.
0.68
0.0223


ATXN1
.
.
0.70
0.0188


AXIN2
0.60
0.0072
0.68
0.0204


AZGP1
0.66
0.0089
0.57
0.0028


BCL2
.
.
0.71
0.0182


BIN1
0.55
0.0005
.
.


BTRC
0.69
0.0397
0.70
0.0251


C7
0.53
0.0002
0.51
<0.0001


CADM1
0.57
0.0012
0.60
0.0032


CASP1
0.64
0.0035
0.72
0.0210


CAV1
0.64
0.0097
0.59
0.0032


CAV2
.
.
0.58
0.0107


CD164
.
.
0.69
0.0260


CD82
0.67
0.0157
0.69
0.0167


CDH1
0.61
0.0012
0.70
0.0210


CDK14
0.70
0.0354
.
.


CDK3
.
.
0.72
0.0267


CDKN1C
0.61
0.0036
0.56
0.0003


CHN1
0.71
0.0214
.
.


COL6A1
0.62
0.0125
0.60
0.0050


COL6A3
0.65
0.0080
0.68
0.0181


CSRP1
0.43
0.0001
0.40
0.0002


CTSB
0.66
0.0042
0.67
0.0051


CTSD
0.64
0.0355
.
.


CTSK
0.69
0.0171
.
.


CTSL1
0.72
0.0402
.
.


CUL1
0.61
0.0024
0.70
0.0120


CXCL12
0.69
0.0287
0.63
0.0053


CYP3A5
0.68
0.0099
0.62
0.0026


DDR2
0.68
0.0324
0.62
0.0050


DES
0.54
0.0013
0.46
0.0002


DHX9
0.67
0.0164
.
.


DLGAP1
.
.
0.66
0.0086


DPP4
0.69
0.0438
0.69
0.0132


DPT
0.59
0.0034
0.51
0.0005


DUSP1
.
.
0.67
0.0214


EDN1
.
.
0.66
0.0073


EDNRA
0.66
0.0148
0.54
0.0005


EIF2C2
.
.
0.65
0.0087


ELK4
0.55
0.0003
0.58
0.0013


ENPP2
0.65
0.0128
0.59
0.0007


EPHA3
0.71
0.0397
0.73
0.0455


EPHB2
0.60
0.0014
.
.


EPHB4
0.73
0.0418
.
.


EPHX3
.
.
0.71
0.0419


ERCC1
0.71
0.0325
.
.


FAM107A
0.56
0.0008
0.55
0.0011


FAM13C
0.68
0.0276
0.55
0.0001


FAS
0.72
0.0404
.
.


FBN1
0.72
0.0395
.
.


FBXW7
0.69
0.0417
.
.


FGF10
0.59
0.0024
0.51
0.0001


FGF7
0.51
0.0002
0.56
0.0007


FGFR2
0.54
0.0004
0.47
<0.0001


FLNA
0.58
0.0036
0.50
0.0002


FLNC
0.45
0.0001
0.40
<0.0001


FLT4
0.61
0.0045
.
.


FOXO1
0.55
0.0005
0.53
0.0005


FOXP3
0.71
0.0275
0.72
0.0354


GHR
0.59
0.0074
0.53
0.0001


GNRH1
0.72
0.0386
.
.


GPM6B
0.59
0.0024
0.52
0.0002


GSN
0.65
0.0107
0.65
0.0098


GSTM1
0.44
<0.0001
0.43
<0.0001


GSTM2
0.42
<0.0001
0.39
<0.0001


HLF
0.46
<0.0001
0.47
0.0001


HPS1
0.64
0.0069
0.69
0.0134


HSPA5
0.68
0.0113
.
.


HSPB2
0.61
0.0061
0.55
0.0004


HSPG2
0.70
0.0359
.
.


ID3
.
.
0.70
0.0245


IGF1
0.45
<0.0001
0.50
0.0005


IGF2
0.67
0.0200
0.68
0.0152


IGFBP2
0.59
0.0017
0.69
0.0250


IGFBP6
0.49
<0.0001
0.64
0.0092


IL6ST
0.56
0.0009
0.60
0.0012


ILK
0.51
0.0010
0.49
0.0004


ITGA1
0.58
0.0020
0.58
0.0016


ITGA3
0.71
0.0286
0.70
0.0221


ITGA5
.
.
0.69
0.0183


ITGA7
0.56
0.0035
0.42
<0.0001


ITGB1
0.63
0.0095
0.68
0.0267


ITGB3
0.62
0.0043
0.62
0.0040


ITPR1
0.62
0.0032
.
.


JUN
0.73
0.0490
0.68
0.0152


KIT
0.55
0.0003
0.57
0.0005


KLC1
.
.
0.70
0.0248


KLK1
.
.
0.60
0.0059


KRT15
0.58
0.0009
0.45
<0.0001


KRT5
0.70
0.0262
0.59
0.0008


LAMA4
0.56
0.0359
0.68
0.0498


LAMB3
.
.
0.60
0.0017


LGALS3
0.58
0.0007
0.56
0.0012


LRP1
0.69
0.0176
.
.


MAP3K7
0.70
0.0233
0.73
0.0392


MCM3
0.72
0.0320
.
.


MMP2
0.66
0.0045
0.60
0.0009


MMP7
0.61
0.0015
0.65
0.0032


MMP9
0.64
0.0057
0.72
0.0399


MPPED2
0.72
0.0392
0.63
0.0042


MTA1
.
.
0.68
0.0095


MTSS1
0.58
0.0007
0.71
0.0442


MVP
0.57
0.0003
0.70
0.0152


MYBPC1
.
.
0.70
0.0359


NCAM1
0.63
0.0104
0.64
0.0080


NCAPD3
0.67
0.0145
0.64
0.0128


NEXN
0.54
0.0004
0.55
0.0003


NFAT5
0.72
0.0320
0.70
0.0177


NUDT6
0.66
0.0102
.
.


OLFML3
0.56
0.0035
0.51
0.0011


OMD
0.61
0.0011
0.73
0.0357


PAGE4
0.42
<0.0001
0.36
<0.0001


PAK6
0.72
0.0335
.
.


PCDHGB7
0.70
0.0262
0.55
0.0004


PGF
0.72
0.0358
0.71
0.0270


PLP2
0.66
0.0088
0.63
0.0041


PPAP2B
0.44
<0.0001
0.50
0.0001


PPP1R12A
0.45
0.0001
0.40
<0.0001


PRIMA1
.
.
0.63
0.0102


PRKAR2B
0.71
0.0226
.
.


PRKCA
0.34
<0.0001
0.42
<0.0001


PRKCB
0.66
0.0120
0.49
<0.0001


PROM1
0.61
0.0030
.
.


PTEN
0.59
0.0008
0.55
0.0001


PTGER3
0.67
0.0293
.
.


PTH1R
0.69
0.0259
0.71
0.0327


PTK2
0.75
0.0461
.
.


PTK2B
0.70
0.0244
0.74
0.0388


PYCARD
0.73
0.0339
0.67
0.0100


RAD9A
0.64
0.0124
.
.


RARB
0.67
0.0088
0.65
0.0116


RGS10
0.70
0.0219
.
.


RHOB
.
.
0.72
0.0475


RND3
.
.
0.67
0.0231


SDHC
0.72
0.0443
.
.


SEC23A
0.66
0.0101
0.53
0.0003


SEMA3A
0.51
0.0001
0.69
0.0222


SH3RF2
0.55
0.0002
0.54
0.0002


SLC22A3
0.48
0.0001
0.50
0.0058


SMAD4
0.49
0.0001
0.50
0.0003


SMARCC2
0.59
0.0028
0.65
0.0052


SMO
0.60
0.0048
0.52
<0.0001


SORBS1
0.56
0.0024
0.48
0.0002


SPARCL1
0.43
0.0001
0.50
0.0001


SRD5A2
0.26
<0.0001
0.31
<0.0001


ST5
0.63
0.0103
0.52
0.0006


STAT5A
0.60
0.0015
0.61
0.0037


STAT5B
0.54
0.0005
0.57
0.0008


SUMO1
0.65
0.0066
0.66
0.0320


SVIL
0.52
0.0067
0.46
0.0003


TGFB1I1
0.44
0.0001
0.43
0.0000


TGFB2
0.55
0.0007
0.58
0.0016


TGFB3
0.57
0.0010
0.53
0.0005


TIMP1
0.72
0.0224
.
.


TIMP2
0.68
0.0198
0.69
0.0206


TIMP3
0.67
0.0105
0.64
0.0065


TMPRSS2
.
.
0.72
0.0366


TNFRSF10A
0.71
0.0181
.
.


TNFSF10
0.71
0.0284
.
.


TOP2B
0.73
0.0432
.
.


TP63
0.62
0.0014
0.50
<0.0001


TPM1
0.54
0.0007
0.52
0.0002


TPM2
0.41
<0.0001
0.40
<0.0001


TPP2
0.65
0.0122
.
.


TRA2A
0.72
0.0318
.
.


TRAF3IP2
0.62
0.0064
0.59
0.0053


TRO
0.57
0.0003
0.51
0.0001


VCL
0.52
0.0005
0.52
0.0004


VIM
0.65
0.0072
0.65
0.0045


WDR19
0.66
0.0097
.
.


WFDC1
0.58
0.0023
0.60
0.0026


ZFHX3
0.69
0.0144
0.62
0.0046


ZNF827
0.62
0.0030
0.53
0.0001









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

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


Patients and Samples


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









TABLE 14







Number of Patients and Events in Analysis Set













Deaths Due to



Patients
Clinical Recurrences
Prostate Cancer













Primary Gleason
416
106
36


Pattern Tumor Tissue





Highest Gleason
405
102
36


Pattern Tumor Tissue





Normal Adjacent
364
81
29


Tissue












Assay Method


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


Statistical Analysis


Using univariate proportional hazards regression (Cox 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






Total Number of
Number of Pairs Predictive of



MicroRNA-
Clinical Recurrence at


Tier
Gene Pairs
False 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





Official
Accession
SEQ

SEQ

SEQ

SEQ



Symbol:
Number:
ID NO
Forward Primer Sequence:
ID NO
Reverse Primer Sequence:
ID NO
Probe Sequence:
ID NO
Amplicon Sequence:







AAMP
NM_001087
   1
GTGTGGCAGGTGGACACTAA
   2
CTCCATCCACTCCAGGTCTC
   3
CGCTTCAAAGGACCA
   4
GTGTGGCAGGTGGACACTAAGGAGGAGGTCTG









GACCTCCTC

GTCCTTTGAAGCGGGAGACCTGGAGTGGATGG











AG





ABCA5
NM_172232
   5
GGTATGGATCCCAAAGCCA
   6
CAGCCCGCTTTCTGTTTTTA
   7
CACATGTGGCGAGCA
   8
GGTATGGATCCCAAAGCCAAACAGCACATGTG









ATTCGAACT

GCGAGCAATTCGAACTGCATTTAAAAACAGAA











AGCGGGCT





ABCB1
NM_000927
   9
AAACACCACTGGAGCATTGA
  10
CAAGCCTGGAACCTATAGCC
  11
CAAGCCTGGAACCTA
  12
AAACACCATGGAGCATTGACTACCAGGCTCGC









TAGCC

CAATGATGCTGCTCAAGTTAAAGGGGCTATAG











GTTCCAG





ABCC1
NM_004996
  13
TCATGGTGCCCGTCAATG
  14
CGATTGTCTTTGCTCTTCATGTG
  15
ACCTGATACGTCTTG
  16
TCATGGTGCCCGTCAATGCTGTGATGGCGATG









GTCTTCATCGCCAT

AAGACCAAGACGTATCAGGTGGCCCACATGAA











GAGCAAAG





ABCC3
NM_003786
  17
TCATCCTGGCGATCTACTTCCT
  18
CCGTTGAGTGGAATCAGCAA
  19
TCTGTCCTGGCTGGA
  20
TCATCCTGGCGATCTACTTCCTCTGGCAGAAC









GTCGCTTTCAT

CTAGGTCCCTCTGTCCTGGCTGGAGTCGCTTT











CATGGTCTTGCTGATTCCACTCAACGG





ABCC4
NM_005845
  21
AGCGCCTGGAATCTACAACT
  22
AGAGCCCCTGGAGAGAAGAT
  23
CGGAGTCCAGTGTTT
  24
AGCGCCTGGAATCTACAACTCGGAGTCCAGTG









TCCCACTTA

TTTTCCCACTTATCATCTTCTCTCCAGGGGCT











CT





ABCC8
NM_000352
  25
CGTCTGTCACTGTGGAGTGG
  26
TGATCCGGTTTAGCAGGC
  27
AGTCTCTTGGCCACC
  28
CGTCTGTCACTGTGGAGTGGACAGGGCTGAAG









TTCAGCCCT

GTGGCCAAGAGACTGCACCGCAGCCTGCTAAA











CCGGATCA





ABCG2
NM_004827
  29
GGTCTCAACGCCATCCTG
  30
CTTGGATCTTTCCTTGCAGC
  31
ACGAAGATTTGCCTC
  32
GGTCTCAACGCCATCCTGGGACCCACAGGTGG









CACCTGTGG

AGGCAAATCTTCGTTATTAGATGTCTTAGCTG











CAAGGAAAG





ABHD2
NM_007011
  33
GTAGTGGGTCTGCATGGATGT
  34
TGAGGGTTGGCACTCAGG
  35
CAGGTGGTCTCCTTT
  36
GTAGTGGGTCTGCATGGATGTTTCAGGGATCA









GATCCCTGA

AAGGAGCCACCTGGGCGCCTGAGTGCCAACCC











TCA





ACE
NM_000789
  37
CCGCTGTACGAGGATTTCA
  38
CCGTGTCTGTGAAGCCGT
  39
TGCCCTCAGCAATGA
  40
CCGCTGTACGAGGATTTCACTGCCCTCAGCAA









AGCCTACAA

TGAAGCCTACAAGCAGGACGGCTTCACAGACA











CGG





ACOX2
NM_003500
  41
ATGGAGGTGCCCAGAACAC
  42
ACTCCGGGTAACTGTGGATG
  43
TGCTCTCAACTTTCC
  44
ATGGAGGTGCCCAGAACACTGCACTCCGCAGG









TGCGGAGTG

AAAGTTGAGAGCATCATCCACAGTTACCCGGA











GT





ACTR2
NM_005722
  45
ATCCGCATTGAAGACCCA
  46
ATCCGCTAGAACTGCACCAC
  47
CCCGCAGAAAGCACA
  48
ATCCGCATTGAAGACCCACCCCGCAGAAAGCA









TGGTATTCC

CATGGTATTCCTGGGTGGTGCAGTTCTAGCGG











AT





ADAM15
NM_003815
  49
GGCGGGATGTGGT
  50
ATTTCTGGGCCTCCG
  51
TCAGCCACAATCACC
  52
GGCGGGATGTGGTAACAGAGACCAAGACTGTG









AACTC

GAGT





ADAMTS1
NM_006988
  53
GGACAGGTGCAAGCTCATCTG
  54
ATCTACAACCTTGGGCTGCAA
  55
CAAGCCAAAGGCATT
  56
GGACAGGTGCAAGCTCATCTGCCAAGCCAAAG









GGCTACTTCTTCG

GCATTGGCTACTTCTTCGTTTTGCAGCCCAAG











GTTGTAGAT





ADH5
NM_000671
  57
ATGCTGTCATCATT
  58
CTGCTTCCTTTCCCTT
  59
TGTCTGCCCATTATC
  60
ATGCTGTCATCATTGTCACGGTTTGTCTGCCC









TTCAT

ATTAT





AFAP1
NM_198595
  61
GATGTCCATCCTT
  62
CAACCCTGATGCCTG
  63
CCTCCAGTGCTGTGT
  64
GATGTCCATCCTTGAAACAGCCTCTTCTGGGA









TCCCA

ACACA





AGTR1
NM_000685
  65
AGCATTGATCGAT
  66
CTACAAGCATTGTGC
  67
ATTGTTCACCCAATG
  68
AGCATTGATCGATACCTGGCTATTGTTCACCC









AAGTC

AATGA





AGTR2
NM_000686
  69
ACTGGCATAGGAA
  70
ATTGACTGGGTCTCTT
  71
CCACCCAGACCCCAT
  72
ACTGGCATAGGAAATGGTATCCAGAATGGAAT









GTAGC

TTTG





AIG1
NM_016108
  73
CGACGGTTCTGCC
  74
TGCTCCTGCTGGGAT
  75
AATCGAGATGAGGAC
  76
CGACGGTTCTGCCCTTTATATTAATCGAGATG









ATCGC

AGGAC





AKAP1
NM_003488
  77
TGTGGTTGGAGAT
  78
GTCTACCCACTGGGC
  79
CTCCACCAGGGACCG
  80
TGTGGTTGGAGATGAAGTGGTGTTGATAAACC









GTTTA

GGTC





AKR1C1
BC040210
  81
GTGTGTGAAGCTG
  82
CTCTGCAGGCGCATA
  83
CCAAATCCCAGGACA
  84
GTGTGTGAAGCTGAATGATGGTCACTTCATGC









GGCAT

CTGTC





AKR1C3
NM_003739
  85
GCTTTGCCTGATGTCTACCAGAA
  86
GTCCAGTCACCGGCATAGAGA
  87
TGCGTCACCATCCAC
  88
GCTTTGCCTGATGTCTACCAGAAGCCCTGTGT









ACACAGGG

GTGGATGGTGACGCAGAGGACGTCTCTATGCC











GGTGACTGG





AKT1
NM_005163
  89
CGCTTCTATGGCG
  90
TCCCGGTACACCACG
  91
CAGCCCTGGACTACC
  92
CGCTTCTATGGCGCTGAGATTGTGTCAGCCCT









TGCAC

GGACT





AKT2
NM_001626
  93
TCCTGCCACCCTTC
  94
GGCGGTAAATTCATC
  95
CAGGTCACGTCCGAG
  96
TCCTGCCACCCTTCAAACCTCAGGTCACGTCC









GTCGA

GAGGT





AKT3
NM_005465
  97
TTGTCTCTGCCTTGGACTATCTAC
  98
CCAGCATTAGATTCTCCAACTTGA
  99
TCACGGTACACAATC
 100
TTGTCTCTGCCTTGGACTATCTACATTCCGGA





A



TTTCCGGA

AAGATTGTGTACCGTGATCTCAAGTTGGAGAA











TCTAATGCTG





ALCAM
NM_001627
 101
GAGGAATATGGAA
 102
GTGGCGGAGATCAAG
 103
CCAGTTCCTGCCGTC
 104
GAGGAATATGGAATCCAAGGGGGCCAGTTCCT









TGCTC

GCCG





ALDH18A1
NM_002860
 105
GATGCAGCTGGAACCCAA
 106
CTCCAGCTCAGTGGGGAA
 107
CCTGAAACTTGCATC
 108
GATGCAGCTGGAACCCAAGCTGCAGCAGGAGA









TCCTGCTGC

TGCAAGTTTCAGGATGTTCCCCACTGAGCTGG











AG





ALDH1A
NM_170696
 109
CACGTCTGTCCCT
 110
GACCGTGGCTCAACT
 111
TCTCTGTAGGGCCCA
 112
CACGTCTGTCCCTCTCTGCTTTCTCTGTAGGG









GCTCT

CCCAG





ALKBH3
NM_139178
 113
TCGCTTAGTCTGC
 114
TCTGAGCCCCAGTTTT
 115
TAAACAGGGCAGTCA
 116
TCGCTTAGTCTGCACCTCAACCGTGCGGAAAG









CTTTC

TGACT





ALOX12
NM_000697
 117
AGTTCCTCAATGG
 118
AGCACTAGCCTGGAG
 119
CATGCTGTTGAGACG
 120
AGTTCCTCAATGGTGCCAACCCCATGCTGTTG









CTCGA

AGACG





ALOX5
NM_000698
 121
GAGCTGCAGGACT
 122
GAAGCCTGAGGACTT
 123
CCGCATGCCGTACAC
 124
GAGCTGCAGGACTTCGTGAACGATGTCTACGT









GTAGA

GTAC





AMACR
NM_203382
 125
GTCTCTGGGCTGTCAGCTTT
 126
TGGGTATAAGATCCAGAACTTGC
 127
TCCATGTGTTTGATT
 128
GTCTCTGGGCTGTCAGCTTTCCTTTCTCCATG









TCTCCTCAGGC

TGTTTGATTTCTCCTCAGGCTGGTAGCAAGTT











CTGGATCTTA





AMPD3
NM_000480
 129
TGGTTCATCCAGCACAAGG
 130
CATAAATCCGGGGCACCT
 131
TACTCTCCCAAGCAT
 132
TGGTTCATCCAGCACAAGGTCTACTCTCCCAA









GCGCTGGATC

CATGCGCTGGATCATCCAGGTGCCCCGGATTT











ATG





ANGPT2
NM_001147
 133
CCGTGAAAGCTGC
 134
TTGCAGTGGGAAGAA
 135
AAGCTGACACAGCCC
 136
CCGTGAAAGCTGCTCTGTAAAAGCTGACACAG









TCCCA

CCCT





ANLN
NM_018685
 137
TGAAAGTCCAAAA
 138
CAGAACCAAGGCTAT
 139
CCAAAGAACTCGTGT
 140
TGAAAGTCCAAAACCAGGAAAATTCCAAAGAA









CCCTC

CTCG





ANPEP
NM_001150
 141
CCACCTTGGACCAAAGTAAAGC
 142
TCTCAGCGTCACCTGGTAGGA
 143
CTCCCCAACACGCTG
 144
CCACCTTGGACCAAAGTAAAGCGTGGAATCGT









AAACCCG

TACCGCCTCCCCAACACGCTGAAACCCGATTC











CTACCGGG





ANAX2
NM_004039
 145
CAAGACACTAAGGGCGACTACCA
 146
CGTGTCGGGCTTCAGTCAT
 147
CCACCACACAGGTAC
 148
CAAGACACTAAGGGCGACTACCAGAAAGCGCT









AGCAGCGCT

GCTGTACCTGTGTGGTGGAGATGACTGAAGCC











CGACACG





APC
NM_000038
 149
GGACAGCAGGAAT
 150
ACCCACTCGATTTGTT
 151
CATTGGCTCCCCGTG
 152
GGACAGCAGGAATGTGTTTCTCCATACAGGT









ACCTG

CACGG





APEX1
NM_001641
 153
GATGAAGCCTTTC
 154
AGGTCTCCACACAGC
 155
CTTTCGGGAAGCCAG
 156
GATGAAGCCTTTCGCAAGTTCCTGAAGGGCC









GCCCT

TGGCTT





APOC1
NM_001645
 157
CCAGCCTGATAAA
 158
CACTCTGAATCCTTGC
 159
AGGACAGGACCTCCC
 160
CCAGCCTGATAAAGGTCCTGCGGGCAGGACA









AACCA

GGACC





APOE
NM_000041
 161
GCCTCAAGAGCTGGTTCG
 162
CCTGCACCTTCTCCACCA
 163
ACTGGCGCTGCATGT
 164
GCCTCAAGAGCTGGTTCGAGCCCCTGGTGGA









CTTCCAC

AGACATGCAGCGCCAGTGGGCCGGGCTGGTG











GAGAAGGTGC





APRT
NM_000485
 165
GAGGTCCTGGAGT
 166
AGGTGCCAGCTTCTC
 167
CCTTAAGCGAGGTCA
 168
GAGGTCCTGGAGTGCGTGAGCCTGGTGGAGC









GCTCC

TGACC





AQP2
NM_000486
 169
GTGTGGGTGCCAG
 170
CCCTTCAGCCCTCTCA
 171
CTCCTTCCCTTCCCC
 172
GTGTGGGTGCCAGTCCTCCTCAGGAGAAGGG









TTCTCC

GAAGG





AR
NM_000044
 173
CGACTTCACCGCA
 174
TGACACAAGTGGGAC
 175
ACCATGCCGCCAGGG
 176
CGACTTCACCGCACCTGATGTGTGGTACCCT









TACCA

GGCGG





ARF1
NM_001658
 177
CAGTAGAGATCCC
 178
ACAAGCACATGGCTA
 179
CTTGTCCTTGGGTCA
 180
CAGTAGAGATCCCCGCAACTCGCTTGTCCTT









CCCTG

GGGTCA





ARHGAP29
NM_004815
 181
CACGGTCTCGTGGTGAAGT
 182
CAGTTGCTTGCCCAGGAC
 183
ATGCCAGACCCAGAC
 184
CACGGTCTCGTGGTGAAGTCAATGCCAGACC









AAAGCATCA

CAGACAAAGCATCAGCTTGTCCTGGGCAAGC











AACTG





ARHGDI
NM_001175
 185
TGGTCCCTAGAAC
 186
TGATGGAGGATCAGA
 187
TAAAACCGGGCTTTC
 188
TGGTCCCTAGAACAAGAGGCTTAAAACCGGG









ACCCA

CTTTC





ASAP2
NM_003887
 189
CGGCCCATCAGCT
 190
CTCTGGCCAAAGATA
 191
CTGGGCTCCAACCAG
 192
CGGCCCATCAGCTTCTACCAGCTGGGCTCCA









CTTCA

ACCAG





ASPN
NM_017680
 193
TGGACTAATCTGT
 194
AAACACCCTTCAACA
 195
AGTATCACCCAGGGT
 196
TGGACTAATCTGTGGGAGCAGTTTATTCCAG









GCAGC

TATCAC





ATM
NM_000051
 197
TGCTTTCTACACAT
 198
GTTGTGGATCGGCTC
 199
CCAGCTGTCTTCGAC
 200
TGCTTTCTACACATGTTCAGGGATTTTTCAC









ACTTC

CAGCTG





ATP5E
NM_006886
 201
CCGCTTTCGCTAC
 202
TGGGAGTATCGGATG
 203
TCCAGCCTGTCTCCA
 204
CCGCTTTCGCTACAGCATGGTGGCCTACTGG









GTAGG

AGACA





ATP5J
NM_001003703
 205
GTCGACCGACTGAAACGG
 206
CTCTACTTCCGGCCCTGG
 207
CTACCCGCCATCGCA
 208
GTCGACCGACTGAAACGGCGGCCCATAATGC









ATGCATTAT

ATTGCGATGGCGGGTAGGCGTGTGGGGGCGG











AGCCAGGGCC





ATXN1
NM_000332
 209
GATCGACTCCAGC
 210
GAACTGTATCACGGC
 211
CGGGCTATGGCTGTC
 212
GATCGACTCCAGCACCGTAGAGAGGATTGAA









TTCAA

GACAG





AURKA
NM_003600
 213
CATCTTCCAGGAG
 214
TCCGACCTTCAATCAT
 215
CTCTGTGGCACCCTG
 216
CATCTTCCAGGAGGACCACTCTCTGTGGCAC









GACTA

CCTGGA





AURKB
NM_004217
 217
AGCTGCAGAAGAG
 218
GCATCTGCCAACTCC
 219
TGACGAGCAGCGAAC
 220
AGCTGCAGAAGAGCTGCACATTTGACGAGCA









AGCC

GCGAA





AXIN2
NM_004655
 221
GGCTATGTCTTTG
 222
ATCCGTCAGCGCATC
 223
ACCAGCGCCAACGAC
 224
GGCTATGTCTTTGCACCAGCCACCAGCGCCA









AGTG

ACGAC





AZGP1
NM_001185
 225
GAGGCCAGCTAGG
 226
CAGGAAGGGCAGCTA
 227
TCTGAGATCCCACAT
 228
GAGGCCAGCTAGGAAGCAAGGGTTGGAGGCA









TGCCT

ATGTG





BAD
NM_032989
 229
GGGTCAGGGGCCT
 230
CTGCTCACTCGGCTC
 231
TGGGCCCAGAGCATG
 232
GGGTCAGGGGCCTCGAGATCGGGCTTGGGCC









TTCCA

CAGAG





BAG5
NM_001015049
 233
ACTCCTGCAATGAACCCTGT
 234
ACAAACAGCTCCCCACGA
 235
ACACCGGATTTAGCT
 236
ACTCCTGCAATGAACCCTGTTGACACCGGAT









CTTGTCGGC

TTAGCTCTTGTCGGCCTTCGTGGGGAGCTGT











TTGT





BAK1
NM_001188
 237
CCATTCCCACCATT
 238
GGGAACATAGACCCA
 239
ACACCCCAGACGTCC
 240
CCATTCCCACCATTCTACCTGAGGCCAGGAC









TGGCC

GTCTGG





BAX
NM_004324
 241
CCGCCGTGGACAC
 242
TTGCCGTCAGAAAAC
 243
TGCCACTCGGAAAAA
 244
CCGCCGTGGACACAGACTCCCCCCGAGAGGT









GACCT

CTTTTT





BBC3
NM_014417
 245
CCTGGAGGGTCCTGTACAAT
 246
CTAATTGGGCTCCATCTCG
 247
CATCATGGGACTCCT
 248
CCTGGAGGGTCCTGTACAATCTCATCATGGG









GCCCTTACC

ACTCCTGCCCTTACCCAGGGGCCACAGAGCC











CCCGAGATGGA





BCL2
NM_000633
 249
CAGATGGACCTAGTACCCACTGAG
 250
CCTATGATTTAAGGGCATTTTTCC
 251
TTCCACGCCGAAGGA
 252
CAGATGGACCTAGTACCCACTGAGATTTCCA





A



CAGCGAT

CGCCGAAGGACAGCGATGGGAAAAATGCCCT











TAAATCATAG





BDKRB1
NM_000710
 253
GTGGCAGAAATCT
 254
GAAGGGCAAGCCCAA
 255
ACCTGGCAGCCTCTG
 256
GTGGCAGAAATCTACCTGGCCAACCTGGCAG









ACTCTG

CCTCT





BGN
NM_001711
 257
GAGCTCCGCAAGG
 258
CTTGTTGTTCACCAGG
 259
CAAGGGTCTCCAGCA
 260
GAGCTCCGCAAGGATGACTTCAAGGGTCTCC









CCTCT

AGCAC





BIK
NM_001197
 261
ATTCCTATGGCTCTGCAATTGTC
 262
GGCAGGAGTGAATGGCTCTTC
 263
CCGGTTAACTGTGGC
 264
ATTCCTATGGCTCTGCAATTGTCACCGGTTA









CTGTGCCC

ACTGTGGCCTGTGCCCAGGAAGAGCCATTCA











CTCCTGCC





BIN1
NM_004305
 265
CCTGCAAAAGGGAACAAGAG
 266
CGTGGTTGACTCTGATCTCG
 267
CTTCGCCTCCAGATG
 268
CCTGCAAAAGGGAACAAGAGCCCTTCGCCTC









GCTCCC

CAGATGGCTCCCCTGCCGCCACCCCCGAGAT











CAGAGTCAAC





BIRC5
NM_001012271
 269
TTCAGGTGGATGAGGAGACA
 270
CACACAGCAGTGGCAAAAG
 271
TCTGCCAGACGCTTC
 272
TTCAGGTGGATGAGGAGACAGAATAGAGTGA









CTATCACTCTATTC

TAGGAAGCGTCTGGCAGATACTCCTTTTGCC











ACTGCTGTGTG





BMP6
NM_001718
 273
GTGCAGACCTTGG
 274
CTTAGTTGGCGCACA
 275
TGAACCCCGAGTATG
 276
GTGCAGACCTTGGTTCACCTTATGAACCCCG









TCCCC

AGTATG





BMPR1B
NM_001203
 277
ACCACTTTGGCCA
 278
GCGGTGTTTGTACCC
 279
ATTCACATTACCATA
 280
ACCACTTTGGCCATCCCTGCATTTGGGGCCG









GCGGC

CTATGG





BRCA1
NM_007294
 281
TCAGGGGGCTAGA
 282
CCATTCCAGTTGATCT
 283
CTATGGGCCCTTCAC
 284
TCAGGGGGCTAGAAATCTGTTGCTATGGGCC









CAACA

CTTCAC





BRCA2
NM_000059
 285
AGTTCGTGCTTTG
 286
AAGGTAAGCTGGGTC
 287
CATTCTTCACTGCTT
 288
AGTTCGTGCTTTGCAAGATGGTGCAGAGCTT









CATAA

TATGAA





BTG1
NM_001731
 289
GAGGTCCGAGCGA
 290
AGTTATTTTCGAGAC
 291
CGCTCGTCTCTTCCT
 292
GAGGTCCGAGCGATGTGACCAGGCCGCCATC









CTCTC

GCTCG





BTG3
NM_006806
 293
CCATATCGCCCAA
 294
CCAGTGATTCCGGTC
 295
CATGGGTACCTCCTC
 296
CCATATCGCCCAATTCCAGTGACATGGGTAC









CTGGA

CTCCTC





BTRC
NM_033637
 297
GTTGGGACACAGT
 298
TGAAGCAGTCAGTTG
 299
CAGTCGGCCCAGGAC
 300
GTTGGGACACAGTTGGTCTGCAGTCGGCCCA









GGTCT

GGACG





BUB1
NM_004336
 301
CCGAGGTTAATCC
 302
AAGACATGGCGCTCT
 303
TGCTGGGAGCCTACA
 304
CCGAGGTTAATCCAGCACGTATGGGGCCAAG









CTTGG

TGTAG





C7
NM_000587
 305
ATGTCTGAGTGTG
 306
AGGCCTTATGCTGGT
 307
ATGCTCTGCCCTCTG
 308
ATGTCTGAGTGTGAGGCGGGCGCTCTGAGAT









CATCT

GCAGA





CACNA1D
NM_000720
 309
AGGACCCAGCTCCATGTG
 310
CCTACATTCCGTGCCATTG
 311
CAGTACACTGGCGTC
 312
AGGACCCAGCTCCATGTGCGTTCTCAGGGAA









CATTCCCTG

TGGACGCCAGTGTACTGCCAATGGCACGGAA











TGTAGG





CADM1
NM_014333
 313
CCACCACCATCCT
 314
GATCCACTGCCCTGA
 315
TCTTCACCTGCTCGG
 316
CCACCACCATCCTTACCATCATCACAGATTC









GAATC

CCGAGC





CADPS
NM_003716
 317
CAGCAAGGAGACT
 318
GGTCCTCTTCTCCACG
 319
CTCCTGGATGGCCAA
 320
CAGCAAGGAGACTGTGCTGAGCTCCTGGATG









ATTTG

GCCAA





CASP1
NM_001223
 321
AACTGGAGCTGAG
 322
CATCTACGCTGTACC
 323
TCACAGGCATGACAA
 324
AACTGGAGCTGAGGTTGACATCACAGGCATG









TGCTG

ACAAT





CASP3
NM_032991
 325
TGAGCCTGAGCAG
 326
CCTTCCTGCGTGGTCC
 327
TCAGCCTGTTCCATG
 328
TGAGCCTGAGCAGAGACATGACTCAGCCTGT









AAGGC

TCCAT





CASP7
NM_033338
 329
GCAGCGCCGAGAC
 330
AGTCTCTCTCCGTCGC
 331
CTTTCGCTAAAGGGG
 332
GCAGCGCCGAGACTTTTAGTTTCGCTTTCGC









CCCCA

TAAAGG





CAV1
NM_001753
 333
GTGGCTCAACATT
 334
CAATGGCCTCCATTTT
 335
ATTTCAGCTGATCAG
 336
GTGGCTCAACATTGTGTTCCCATTTCAGCTG









TGGGC

ATCAGT





CAV2
NM_198212
 337
CTTCCCTGGGACG
 338
CTCCTGGTCACCCTTC
 339
CCCGTACTGTCATGC
 340
CTTCCCTGGGACGACTTGCCAGCTCTGAGGC









CTCAG

ATGAC





CCL2
NM_002982
 341
CGCTCAGCCAGATGCAATC
 342
GCACTGAGATCTTCCTATTGGTGA
 343
TGCCCCAGTCACCTG
 344
CGCTCAGCCAGATGCAATCAATGCCCCAGTC







A

CTGTTA

ACCTGCTGTTATAACTTCACCAATAGGAAGA











TCTCAGTGC





CCL5
NM_002985
 345
AGGTTCTGAGCTC
 346
ATGCTGACTTCCTTCC
 347
ACAGAGCCCTGGCAA
 348
AGGTTCTGAGCTCTGGCTTTGCCTTGGCTTT









AGCC

GCCAGG





CCNB1
NM_031996
 349
TTCAGGTTGTTGCAGGAGAC
 350
CATCTTCTTGGGCACACAAT
 351
TGTCTCCATTATTGA
 352
TTCAGGTTGTTGCAGGAGACCATGTACATGA









TCGGTTCATGCA

CTGTCTCCATTATTGATCGGTTCATGCAGAA











TAATTGTGTGCC





CCND1
NM_001758
 353
GCATGTTCGTGGC
 354
CGGTGTAGATGCACA
 355
AAGGAGACCATCCCC
 356
GCATGTTCGTGGCCTCTAAGATGAAGGAGAC









CTGAC

CATCC





CCNE2
NM_057749
 357
ATGCTGTGGCTCCTTCCTAACT
 358
ACCCAAATTGTGATATACAAAAAG
 359
TACCAAGCAACCTAC
 360
ATGCTGTGGCTCCTTCCTAACTGGGGCTTTC







GTT

ATGTCAAGAAAGCCC

TTGACATGTAGGTTGCTTGGTAATAACCTTT











TTGTATATCACA





CCNH
NM_001239
 361
GAGATCTTCGGTG
 362
CTGCAGACGAGAACC
 363
CATCAGCGTCCTGGC
 364
GAGATCTTCGGTGGGGGTACGGGTGTTTTAC









GTAAA

GCCAG





CCR1
NM_001295
 365
TCCAAGACCCAAT
 366
TCGTAGGCTTTCGTG
 367
ACTCACCACACCTGC
 368
TCCAAGACCCAATGGGAATTCACTCACCACA









AGCCT

CCTGC





CD164
NM_006016
 369
CAACCTGTGCGAA
 370
ACACCCAAGACCAGG
 371
CCTCCAATGAAACTG
 372
CAACCTGTGCGAAAGTCTACCTTTGATGCAG









GCTGC

CCAGTT





CD1A
NM_001763
 373
GGAGTGGAAGGAACTGGAAA
 374
TCATGGGCGTATCTACGAAT
 375
CGCACCATTCGGTCA
 376
GGAGTGGAAGGAACTGGAAACATTATTCCGT









TTTGAGG

ATACGCACCATTCGGTCATTTGAGGGAATTC











GTAGATACGCC





CD276
NM_001024736
 377
CCAAAGGATGCGATACACAG
 378
GGATGACTTGGGAATCATGTC
 379
CCACTGTGCAGCCTT
 380
CCAAAGGATGCGATACACAGACCACTGTGCA









ATTTCTCCAATG

GCCTTATTTCTCCAATGGACATGATTCCCAA











GTCATCC





CD44
NM_000610
 381
GGCACCACTGCTT
 382
GATGCTCATGGTGAA
 383
ACTGGAACCCAGAAG
 384
GGCACCACTGCTTATGAAGGAAACTGGAACC









CACA

CAGAA





CD68
NM_001251
 385
TGGTTCCCAGCCC
 386
CTCCTCCACCCTGGGT
 387
CTCCAAGCCCAGATT
 388
TGGTTCCCAGCCCTGTGTCCACCTCCAAGCC









CAGAT

CAGATT





CD82
NM_002231
 389
GTGCAGGCTCAGGTGAAGTG
 390
GACCTCAGGGCGATTCATGA
 391
TCAGCTTCTACAACT
 392
GTGCAGGCTCAGGTGAAGTGCTGCGGCTGGG









GGACAGACAACGCTG

TCAGCTTCTACAACTGGACAGACAACGCTGA











GCTCATGAAT





CDC20
NM_001255
 393
TGGATTGGAGTTC
 394
GCTTGCACTCCACAG
 395
ACTGGCCGTGGCACT
 396
TGGATTGGAGTTCTGGGAATGTACTGGCCGT









GGACA

GGCAC





CDC25B
NM_021873
 397
GCTGCAGGACCAG
 398
TAGGGCAGCTGGCTT
 399
CTGCTACCTCCCTTG
 400
GCTGCAGGACCAGTGAGGGGCCTGCGCCAGT









CCTTT

CCTGC





CDC6
NM_001254
 401
GCAACACTCCCCA
 402
TGAGGGGGACCATTC
 403
TTGTTCTCCACCAAA
 404
GCAACACTCCCCATTTACCTCCTTGTTCTCC









GCAAG

ACCAAA





CDH1
NM_004360
 405
TGAGTGTCCCCCGGTATCTTC
 406
CAGCCGCTTTCAGATTTTCAT
 407
TGCCAATCCCGATGA
 408
TGAGTGTCCCCCGGTATCTTCCCCGCCCTGC









AATTGGAAATTT

CAATCCCGATGAAATTGGAAATTTTATTGAT











GAAAATCTGAAA





CDH10
NM_006727
 409
TGTGGTGCAAGTC
 410
TGTAAATGACTCTGG
 411
ATGCCGATGACCCTT
 412
TGTGGTGCAAGTCACAGCTACAGATGCCGAT









CATAT

GACCC





CDH11
NM_001797
 413
GTCGGCAGAAGCA
 414
CTACTCATGGGCGGG
 415
CCTTCTGCCCATAGT
 416
GTCGGCAGAAGCAGGACTTGTACCTTCTGCC









GATCA

CATAG





CDH19
NM_021153
 417
AGTACCATAATGC
 418
AGACTGCCTGTATAG
 419
ACTCGGAAAACCACA
 420
AGTACCATAATGCGGGAACGCAAGACTCGGA









AGCG

AAACC





CDH5
NM_001795
 421
ACAGGAGACGTGT
 422
CAGCAGTGAGGTGGT
 423
TATTCTCCCGGTCCA
 424
ACAGGAGACGTGTTCGCCATTGAGAGGCTGG









GCCTC

ACCGG





CDH7
NM_033646
 425
GTTTGACATGGCT
 426
AGTCACATCCCTCCG
 427
ACCTCAACGTCATCC
 428
GTTTGACATGGCTGCACTGAGAAACCTCAAC









GAGAC

GTCATC





CDK14
NM_012395
 429
GCAAGGTAAATGG
 430
GATAGCTGTGAAAGG
 431
CTTCCTGCAGCCTGA
 432
GCAAGGTAAATGGGAAGTTGGTAGCTCTGAA









TCACC

GGTGA





CDK2
NM_001798
 433
AATGCTGCACTACGACCCTA
 434
TTGGTCACATCCTGGAAGAA
 435
CCTTGGCCGAAATCC
 436
AATGCTGCACTACGACCCTAACAAGCGGATT









GCTTGT

TCGGCCAAGGCAGCCCTGGCTCACCCTTTCT











TCCAGGATGTG





CDK3
NM_001258
 437
CCAGGAAGGGACT
 438
GTTGCATGAGCAGGT
 439
CTCTGGCTCCAGATT
 440
CCAGGAAGGGACTGGAAGAGATTGTGCCCAA









GGGCA

TCTGG





CDK7
NM_001799
 441
GTCTCGGGCAAAG
 442
CTCTGGCCTTGTAAA
 443
CCTCCCCAAGGAAGT
 444
GTCTCGGGCAAAGCGTTATGAGAAGCTGGAC









CCAGC

TTCCT





CDKN1A
NM_000389
 445
TGGAGACTCTCAG
 446
GGCGTTTGGAGTGGT
 447
CGGCGGCAGACCAGC
 448
TGGAGACTCTCAGGGTCGAAAACGGCGGCAG









ATGA

ACCAG





CDKN1C
NM_000076
 449
CGGCGATCAAGAA
 450
CAGGCGCTGATCTCT
 451
CGGGCCTCTGATCTC
 452
CGGCGATCAAGAAGCTGTCCGGGCCTCTGAT









CGATT

CTCCG





CDKN2B
NM_004936
 453
GACGCTGCAGAGC
 454
GCGGGAATCTCTCCT
 455
CACAGGATGCTGGCC
 456
GACGCTGCAGAGCACCTTTGCACAGGATGCT









TTTGC

GGCCT





CDKN2C
NM_001262
 457
GAGCACTGGGCAA
 458
CAAAGGCGAACGGGA
 459
CCTGTAACTTGAGGG
 460
GAGCACTGGGCAATCGTTACGACCTGTAACT









CCACC

TGAGG





CDKN3
NM_005192
 461
TGGATCTCTACCA
 462
ATGTCAGGAGTCCCT
 463
ATCACCCATCATCAT
 464
TGGATCTCTACCAGCAATGTGGAATTATCAC









CCAAT

CCATCA





CDS2
NM_003818
 465
GGGCTTCTTTGCT
 466
ACAGGGCAGACAAAG
 467
CCCGGACATCACATA
 468
GGGCTTCTTTGCTACTGTGGTGTTTGGCCTT









GGACA

CTGCTG





CENPF
NM_016343
 469
CTCCCGTCAACAG
 470
GGGTGAGTCTGGCCT
 471
ACACTGGACCAGGAG
 472
CTCCCGTCAACAGCGTTCTTTCCAAACACTG









TGCAT

GACCAG





CHAF1A
NM_005483
 473
GAACTCAGTGTAT
 474
GCTCTGTAGCACCTG
 475
TGCACGTACCAGCAC
 476
GAACTCAGTGTATGAGAAGCGGCCTGACTTC









ATCCT

AGGAT





CHN1
NM_001822
 477
TTACGACGCTCGT
 478
TCTCCCTGATGCACAT
 479
CCACCATTGGCCGCT
 480
TTACGACGCTCGTGAAAGCACATACCACTAA









TAGTG

GCGGC





CHRAC1
NM_017444
 481
TCTCGCTGCCTCTA
 482
CCTGGTTGATGCTGG
 483
ATCCGGGTCATCATG
 484
TCTCGCTGCCTCTATCCCGCATCCGGGTCAT









AAGAG

CATGAA





CKS2
NM_001827
 485
GGCTGGACGTGGT
 486
CGCTGCAGAAAATGA
 487
CTGCGCCCGCTCTTC
 488
GGCTGGACGTGGTTTTGTCTGCTGCGCCCGC









GCG

TCTTCG





CLDN3
NM_001306
 489
ACCAACTGCGTGC
 490
GGCGAGAAGGAACAG
 491
CAAGGCCAAGATCAC
 492
ACCAACTGCGTGCAGGACGACACGGCCAAGG









CATCG

CCAAG





CLTC
NM_004859
 493
ACCGTATGGACAG
 494
TGACTACAGGATCAG
 495
TCTCACATGCTGTAC
 496
ACCGTATGGACAGCCACAGCCTGGCTTTGGG









CCAAA

TACAG





COL11A
NM_001854
 497
GCCCAAGAGGGGA
 498
GGACCTGGGTCTCCA
 499
CTGCTCGACCTTTGG
 500
GCCCAAGAGGGGAAGATGGCCCTGAAGGACC









GTCCT

CAAAG





COL1A1
NM_000088
 501
GTGGCCATCCAGC
 502
CAGTGGTAGGTGATG
 503
TCCTGCGCCTGATGT
 504
GTGGCCATCCAGCTGACCTTCCTGCGCCTGA









CCACC

TGTCCA





COL1A2
NM_000089
 505
CAGCCAAGAACTGGTATAGGAGCT
 506
AAACTGGCTGCCAGCATTG
 507
TCTCCTAGCCAGACG
 508
CAGCCAAGAACTGGTATAGGAGCTCCAAGGA









TGTTTCTTGTCCTTG

CAAGAAACACGTCTGGCTAGGAGAAACTATC











AATGCTGGCA





COL3A1
NM_000090
 509
GGAGGTTCTGGAC
 510
ACCAGGACTGCCACG
 511
CTCCTGGTCCCCAAG
 512
GGAGGTTCTGGACCTGCTGGTCCTCCTGGTC









GTGTC

CCAAG





COL4A1
NM_001845
 513
ACAAAGGCCTCCC
 514
GAGTCCCAGGAAGAC
 515
CTCCTTTGACACCAG
 516
ACAAAGGCCTCCCAGGATTGGATGGCATCCC









GGATG

TGGTG





COL5A1
NM_000093
 517
CTCCCTGGGAAAG
 518
CTGGACCAGGAAGCC
 519
CCAGGGAAACCACGT
 520
CTCCCTGGGAAAGATGGCCCTCCAGGATTAC









AATCC

GTGGT





COL5A2
NM_000393
 521
GGTCGAGGAACCC
 522
GCCTGGAGGTCCAAC
 523
CCAGGAAATCCTGTA
 524
GGTCGAGGAACCCAAGGTCCGCCTGGTGCTA









GCACC

CAGGA





COL6A1
NM_001848
 525
GGAGACCCTGGTG
 526
TCTCCAGGGACACCA
 527
CTTCTCTTCCCTGAT
 528
GGAGACCCTGGTGAAGCTGGCCCGCAGGGTG









CACCC

ATCAG





COL6A3
NM_004369
 529
GAGAGCAAGCGAG
 530
AACAGGGAACTGGCC
 531
CCTCTTTGACGGCTC
 532
GAGAGCAAGCGAGACATTCTGTTCCTCTTTG









AGCCA

ACGGCT





COL8A1
NM_001850
 533
TGGTGTTCCAGGG
 534
CCCTGTAAACCCTGA
 535
CCTAAGGGAGAGCCA
 536
TGGTGTTCCAGGGCTTCTCGGACCTAAGGGA









GGAA

GAGCC





COL9A2
NM_001852
 537
GGGAACCATCCAG
 538
ATTCCGGGTGGACAG
 539
ACACAGGAAATCCGC
 540
GGGAACCATCCAGGGTCTGGAAGGCAGTGCG









ACTGC

GATTT





CRISP3
NM_006061
 541
TCCCTTATGAACA
 542
AACCATTGGTGCATA
 543
TGCCAGTTGCCCAGA
 544
TCCCTTATGAACAAGGAGCACCTTGTGCCAG









TAACT

TTGCCC





CSF1
NM_000757
 545
TGCAGCGGCTGATTGACA
 546
CAACTGTTCCTGGTCTACAAACTC
 547
TCAGATGGAGACCTC
 548
TGCAGCGGCTGATTGACAGTCAGATGGAGAC







A

GTGCCAAATTACA

CTCGTGCCAAATTACATTTGAGTTTGTAGAC











CAGGAACAGTT





CSK
NM_004383
 549
CCTGAACATGAAG
 550
CATCACGTCTCCGAA
 551
TCCCGATGGTCTGCA
 552
CCTGAACATGAAGGAGCTGAAGCTGCTGCAG









GCAGC

ACCAT





CSRP1
NM_004078
 553
ACCCAAGACCCTG
 554
GCAGGGGTGGAGTGA
 555
CCACCCTTCTCCAGG
 556
ACCCAAGACCCTGCCTCTTCCACTCCACCCT









GACCC

TCTCCA





CTGF
NM_001901
 557
GAGTTCAAGTGCCCTGACG
 558
AGTTGTAATGGCAGGCACAG
 559
AACATCATGTTCTTC
 560
GAGTTCAAGTGCCCTGACGGCGAGGTCATGA









TTCATGACCTGCGC

AGAAGAACATGATGTTCATCAAGACCTGTGC











CTGCCATTACA





CTHRC1
NM_138455
 561
TGGCTCACTTCGG
 562
TCAGCTCCATTGAAT
 563
CAACGCTGACAGCAT
 564
TGGCTCACTTCGGCTAAAATGCAGAAATGCA









GCATT

TGCTGT





CTNNA1
NM_001903
 565
CGTTCCGATCCTCTATACTGCAT
 566
AGGTCCCTGTTGGCCTTATAGG
 567
ATGCCTACAGCACCC
 568
CGTTCCGATCCTCTATACTGCATCCCAGGCA









TGATGTCGCA

TGCCTACAGCACCCTGATGTCGCAGCCTATA











AGGCCAACAGG





CTNNB1
NM_001904
 569
GGCTCTTGTGCGTACTGTCCTT
 570
TCAGATGACGAAGAGCACAGATG
 571
AGGCTCAGTGATGTC
 572
GGCTCTTGTGCGTACTGTCCTTCGGGCTGGT









TTCCCTGTCACCAG

GACAGGGAAGACATCACTGAGCCTGCCATCT











GTGCTCTTCGTC





CTNND1
NM_001331
 573
CGGAAACTTCGGG
 574
CTGAATCCTTCTGCCC
 575
TTGATGCCCTCATTT
 576
CGGAAACTTCGGGAATGTGATGGTTTAGTTG









TCATT

ATGCC





CTNND2
NM_001332
 577
GCCCGTCCCTACA
 578
CTCACACCCAGGAGT
 579
CTATGAAACGAGCCA
 580
GCCCGTCCCTACAGTGAACTGAACTATGAAA









CTACC

CGAGC





CTSB
NM_001908
 581
GGCCGAGATCTAC
 582
GCAGGAAGTCCGAAT
 583
CCCCGTGGAGGGAGC
 584
GGCCGAGATCTACAAAAACGGCCCCGTGGAG









TTTCT

GGAGC





CTSD
NM_001909
 585
GTACATGATCCCCTGTGAGAAGGT
 586
GGGACAGCTTGTAGCCTTTGC
 587
ACCCTGCCCGCGATC
 588
GTACATGATCCCCTGTGAGAAGGTGTCCACC









ACACTGA

CTGCCCGCGATCACACTGAAGCTGGGAGGCA











AAGGCTACAAG





CTSK
NM_000396
 589
AGGCTTCTCTTGG
 590
CCACCTCTTCACTGGT
 591
CCCCAGGTGGTTCAT
 592
AGGCTTCTCTTGGTGTCCATACATATGAACT









AGCCA

GGCTAT





CTSL2
NM_001333
 593
TGTCTCACTGAGC
 594
ACCATTGCAGCCCTG
 595
CTTGAGGACGCGAAC
 596
TGTCTCACTGAGCGAGCAGAATCTGGTGGAC









AGTCC

TGTTC





CTSS
NM_004079
 597
TGACAACGGCTTT
 598
TCCATGGCTTTGTAG
 599
TGATAACAAGGGCAT
 600
TGACAACGGCTTTCCAGTACATCATTGATAA









CGACT

CAAGG





CUL1
NM_003592
 601
ATGCCCTGGTAAT
 602
GCGACCACAAGCCTT
 603
CAGCCACAAAGCCAG
 604
ATGCCCTGGTAATGTCTGCATTCAACAATGA









CGTCA

CGCTGG





CXCL12
NM_000609
 605
GAGCTACAGATGC
 606
TTTGAGATGCTTGAC
 607
TTCTTCGAAAGCCAT
 608
GAGCTACAGATGCCCATGCCGATTCTTCGAA









GTTGC

AGCCA





CXCR4
NM_003467
 609
TGACCGCTTCTAC
 610
AGGATAAGGCCAACC
 611
CTGAAACTGGAACAC
 612
TGACCGCTTCTACCCCAATGACTTGTGGGTG









AACCA

GTTGTG





CXCR7
NM_020311
 613
CGCCTCAGAACGATGGAT
 614
GTTGCATGGCCAGCTGAT
 615
CTCAGAGCCAGGGAA
 616
CGCCTCAGAACGATGGATCTGCATCTCTTCG









CTTCTCGGA

ACTACTCAGAGCCAGGGAACTTCTCGGACAT











CAGCTGGCCAT





CYP3A5
NM_000777
 617
TCATTGCCCAGTA
 618
GACAGGCTTGCCTTT
 619
TCCCGCCTCAAGTTT
 620
TCATTGCCCAGTATGGAGATGTATTGGTGAG









CTCAC

AAACTT





CYR61
NM_001554
 621
TGCTCATTCTTGAG
 622
GTGGCTGCATTAGTG
 623
CAGCACCCTTGGCAG
 624
TGCTCATTCTTGAGGAGCATTAAGGTATTTC









TTTCG

GAAACT





DAG1
NM_004393
 625
GTGACTGGGCTCA
 626
ATCCCACTTGTGCTCC
 627
CAAGTCAGAGTTTCC
 628
GTGACTGGGCTCATGCCTCCAAGTCAGAGTT









CTGGT

TCCCTG





DAP
NM_004394
 629
CCAGCCTTTCTGG
 630
GACCAGGTCTGCCTC
 631
CTCACCAGCTGGCAG
 632
CCAGCCTTTCTGGTGCTGTTCTCCAGTTCAC









ACGTG

GTCTGC





DAPK1
NM_004938
 633
CGCTGACATCATG
 634
TCTCTTTCAGCAACGA
 635
TCATATCCAAACTCG
 636
CGCTGACATCATGAATGTTCCTCGACCGGCT









CCTCC

GGAGG





DARC
NM_002036
 637
GCCCTCATTAGTC
 638
CAGACAGAAGGGCTG
 639
TCAGCGCCTGTGCTT
 640
GCCCTCATTAGTCCTTGGCTCTTATCTTGGA









CCAAG

AGCACA





DDIT4
NM_019058
 641
CCTGGCGTCTGTC
 642
CGAAGAGGAGGTGGA
 643
CTAGCCTTTGGGACC
 644
CCTGGCGTCTGTCCTCACCATGCCTAGCCTT









GCTTC

TGGGAC





DDR2
NM_001014796
 645
CTATTACCGGATCCAGGGC
 646
CCCAGCAAGATACTCTCCCA
 647
AGTGCTCCCTATCCG
 648
CTATTACCGGATCCAGGGCCGGGCAGTGCTC









CTGGATGTC

CCTATCCGCTGGATGTCTTGGGAGAGTATCT











TGCTGGG





DES
NM_001927
 649
ACTTCTCACTGGC
 650
GCTCCACCTTCTCGTT
 651
TGAACCAGGAGTTTC
 652
ACTTCTCACTGGCCGACGCGGTGAACCAGGA









TGACC

GTTTCT





DHRS9
NM_005771
 653
GGAGAAAGGTCTC
 654
CAGTCAGTGGGAGCC
 655
ATCAATAATGCTGGT
 656
GGAGAAAGGTCTCTGGGGTCTGATCAATAAT









GTTCC

GCTGG





DHX9
NM_001357
 657
GTTCGAACCATCT
 658
TCCAGTTGGATTGTG
 659
CCAAGGAACCACACC
 660
GTTCGAACCATCTCAGCGACAAAACCAAGTG









CACTT

GGTGT





DIAPH1
NM_005219
 661
CAAGCAGTCAAGG
 662
AGTTTTGCTCGCCTCA
 663
TTCTTCTGTCTCCCG
 664
CAAGCAGTCAAGGAGAACCAGAAGCGGCGGG









CCGCT

AGAC





DICER1
NM_177438
 665
TCCAATTCCAGCA
 666
GGCAGTGAAGGCGAT
 667
AGAAAAGCTGTTTGT
 668
TCCAATTCCAGCATCACTGTGGAGAAAAGCT









CTCCC

GTTTGT





DIO2
NM_013989
 669
CTCCTTTCACGAG
 670
AGGAAGTCAGCCACT
 671
ACTCTTCCACCAGTT
 672
CTCCTTTCACGAGCCAGCTGCCAGCCTTCCG









TGCGG

CAAACT





DLC1
NM_006094
 673
GATTCAGACGAGG
 674
CACCTCTTGCTGTCCC
 675
AAAGTCCATTTGCCA
 676
GATTCAGACGAGGATGAGCCTTGTGCCATCA









CTGAT

GTGGC





DLGAP1
NM_004746
 677
CTGCTGAGCCCAG
 678
AGCCTGGAAGGAGTT
 679
CGCAGACCACCCATA
 680
CTGCTGAGCCCAGTGGAGCACCACCCCGCAG









CTACA

ACCAC





DLL4
NM_019074
 681
CACGGAGGTATAA
 682
AGAAGGAAGGTCCAG
 683
CTACCTGGACATCCC
 684
CACGGAGGTATAAGGCAGGAGCCTACCTGGA









TGCTC

CATCC





DNM3
NM_015569
 685
CTTTCCCACCCGG
 686
AAGGACCTTCTGCAG
 687
CATATCGCTGACCGA
 688
CTTTCCCACCCGGCTTACAGACATATCGCTG









ATGGG

ACCGAA





DPP4
NM_001935
 689
GTCCTGGGATCGG
 690
GTACTCCCACCGGGA
 691
CGGCTATTCCACACT
 692
GTCCTGGGATCGGGAAGTGGCGTGTTCAAGT









TGAAC

GTGGA





DPT
NM_001937
 693
CACCTAGAAGCCT
 694
CAGTAGCTCCCCAGG
 695
TTCCTAGGAAGGCTG
 696
CACCTAGAAGCCTGCCCACGATTCCTAGGAA









GCAGA

GGCTG





DUSP1
NM_004417
 697
AGACATCAGCTCC
 698
GACAAACACCCTTCC
 699
CGAGGCCATTGACTT
 700
AGACATCAGCTCCTGGTTCAACGAGGCCATT









CATAG

GACTTC





DUSP6
NM_001946
 701
CATGCAGGGACTG
 702
TGCTCCTACCCTATCA
 703
TCTACCCTATGCGCC
 704
CATGCAGGGACTGGGATTCGAGGACTTCCAG









TGGAA

GCGCA





DVL1
NM_004421
 705
TCTGTCCCACCTG
 706
TCAGACTGTTGCCGG
 707
CTTGGAGCAGCCTGC
 708
TCTGTCCCACCTGCTGCTGCCCCTTGGAGCA









ACCTT

GCCTGC





DYNLL1
NM_001037494
 709
GCCGCCTACCTCACAGAC
 710
GCCTGACTCCAGCTCTCCT
 711
ACCCACGTCAGTGAG
 712
GCCGCCTACCTCACAGACTTGTGAGCACTCA









TGCTCACAA

CTGACGTGGGTAGCGCCCAGGGCCTGCGGGG











CGCAGGAGAG





EBNA1BP2
NM_006824
 713
TGCGGCGAGATGGACACT
 714
GTGACAAGGGATTCATCGGATT
 715
CCCGCTCTCGGATTC
 716
TGCGGCGAGATGGACACTCCCCCGCTCTCGG









GGAGTCG

ATTCGGAGTCGGAATCCGATGAATCCCTTGT











CAC





ECE1
NM_001397
 717
ACCTTGGGATCTG
 718
GGACCAGGACCTCCA
 719
TCCACTCTCGATACC
 720
ACCTTGGGATCTGCCTCCAAGCTGGTGCAGG









CTGCA

GTATC





EDN1
NM_001955
 721
TGCCACCTGGACA
 722
TGGACCTAGGGCTTC
 723
CACTCCCGAGCACGT
 724
TGCCACCTGGACATCATTTGGGTCAACACTC









TGTTC

CCGAGC





EDNRA
NM_001957
 725
TTTCCTCAAATTTG
 726
TTACACATCCAACCA
 727
CCTTTGCCTCAGGGC
 728
TTTCCTCAAATTTGCCTCAAGATGGAAACCC









ATCCT

TTTGCC





EFNB2
NM_004093
 729
TGACATTATCATCCCGCTAAGGA
 730
GTAGTCCCCGCTGACCTTCTC
 731
CGGACAGCGTCTTCT
 732
TGACATTATCATCCCGCTAAGGACTGCGGAC









GCCCTCACT

AGCGTCTTCTGCCCTCACTACGAGAAGGTCA











GCGGGGACTA





EGF
NM_001963
 733
CTTTGCCTTGCTCTGTCACAGT
 734
AAATACCTGACACCCTTATGACAA
 735
AGAGTTTAACAGCCC
 736
CTTTGCCTTGCTCTGTCACAGTGAAGTCAGC







ATT

TGCTCTGGCTGACTT

CAGAGCAGGGCTGTTAAACTCTGTGAAATTT











GTCATAAGGGTG





EGR1
NM_001964
 737
GTCCCCGCTGCAGATCTCT
 738
CTCCAGCTTAGGGTAGTTGTCCAT
 739
CGGATCCTTTCCTCA
 740
GTCCCCGCTGCAGATCTCTGACCCGTTCGGA









CTCGCCCA

TCCTTTCCTCACTCGCCCACCATGGACAACT











ACCCTAAGCTGG





EGR3
NM_004430
 741
CCATGTGGATGAATGAGGTG
 742
TGCCTGAGAAGAGGTGAGGT
 743
ACCCAGTCTCACCTT
 744
CCATGTGGATGAATGAGGTGTCTCCTTTCCA









CTCCCCACC

TACCCAGTCTCACCTTCTCCCCACCCTACCT











CACCTCTTCTCA





EIF2C2
NM_012154
 745
GCACTGTGGGCAG
 746
ATGTTTGGTGACTGG
 747
CGGGTCACATTGCAG
 748
GCACTGTGGGCAGATGAAGAGGAAGTACCGC









ACACG

GTCTG





EIF2S3
NM_001415
 749
CTGCCTCCCTGATT
 750
GGTGGCAAGTGCCTG
 751
TCTCGTGCTTCAGCC
 752
CTGCCTCCCTGATTCAAGTGATTCTCGTGCT









TCCCA

TCAGCC





EIF3H
NM_003756
 753
CTCATTGCAGGCCAGATAAA
 754
GCCATGAAGAGCTTGCCTA
 755
CAGAACATCAAGGAG
 756
CTCATTGCAGGCCAGATAAACACTTACTGCC









TTCACTGCCCA

AGAACATCAAGGAGTTCACTGCCCAAAACTT











AGGCAAGCTC





EIF4E
NM_001968
 757
GATCTAAGATGGCGACTGTCGAA
 758
TTAGATTCCGTTTTCTCCTCTTCT
 759
ACCACCCCTACTCCT
 760
GATCTAAGATGGCGACTGTCGAACCGGAAAC







G

AATCCCCCGACT

CACCCCTACTCCTAATCCCCCGACTACAGAA











GAGGAGAAAA





EIF5
NM_001969
 761
GAATTGGTCTCCA
 762
TCCAGGTATATGGCT
 763
CCACTTGCACCCGAA
 764
GAATTGGTCTCCAGCTGCCTTTGATCAAGAT









TCTTG

TCGGGT





ELK4
NM_001973
 765
GATGTGGAGAATG
 766
AGTCATTGCGGCTAG
 767
ATAAACCACCTCAGC
 768
GATGTGGAGAATGGAGGGAAAGATAAACCAC









CTGGT

CTCAG





ENPP2
NM_006209
 769
CTCCTGCGCACTA
 770
TCCCTGGATAATTGG
 771
TAACTTCCTCTGGCA
 772
CTCCTGCGCACTAATACCTTCAGGCCAACCA









TGGTT

TGCCAG





ENY2
NM_020189
 773
CCTCAAAGAGTTG
 774
CCTCTTTACAGTGTGC
 775
CTGATCCTTCCAGCC
 776
CCTCAAAGAGTTGCTGAGAGCTAAATTAATT









ACATT

GAATGT





EPHA2
NM_004431
 777
CGCCTGTTCACCA
 778
GTGGCGTGCCTCGAA
 779
TGCGCCCGATGAGAT
 780
CGCCTGTTCACCAAGATTGACACCATTGCGC









CACCG

CCGATG





EPHA3
NM_005233
 781
CAGTAGCCTCAAG
 782
TTCGTCCCATATCCAG
 783
TATTCCAAATCCGAG
 784
CAGTAGCCTCAAGCCTGACACTATATACGTA









CCCGA

TTCCAA





EPHB2
NM_004442
 785
CAACCAGGCAGCT
 786
GTAATGCTGTCCACG
 787
CACCTGATGCATGAT
 788
CAACCAGGCAGCTCCATCGGCAGTGTCCATC









GGACA

ATGCA





EPHB4
NM_004444
 789
TGAACGGGGTATCCTCCTTA
 790
AGGTACCTCTCGGTCAGTGG
 791
CGTCCCATTTGAGCC
 792
TGAACGGGGTATCCTCCTTAGCCACGGGGCC









TGTCAATGT

CGTCCCATTTGAGCCTGTCAATGTCACCACT











GACCGAGAGGT





ERBB2
NM_004448
 793
CGGTGTGAGAAGT
 794
CCTCTCGCAAGTGCT
 795
CCAGACCATAGCACA
 796
CGGTGTGAGAAGTGCAGCAAGCCCTGTGCCC









CTCGG

GAGTG





ERBB3
NM_001982
 797
CGGTTATGTCATGCCAGATACAC
 798
GAACTGAGACCCACTGAAGAAAGG
 799
CCTCAAAGGTACTCC
 800
CGGTTATGTCATGCCAGATACACACCTCAAA









CTCCTCCCGG

GGTACTCCCTCCTCCCGGGAAGGCACCCTTT











CTTCAGTGGGTC





ERBB4
NM_005235
 801
TGGCTCTTAATCAGTTTCGTTACC
 802
CAAGGCATATCGATCCTCATAAAG
 803
TGTCCCACGAATAAT
 804
TGGCTCTTAATCAGTTTCGTTACCTGCCTCT





T

T

GCGTAAATTCTCCAG

GGAGAATTTACGCATTATTCGTGGGACAAAA











CTTTATGAGGAT





ERCC1
NM_001983
 805
GTCCAGGTGGATG
 806
CGGCCAGGATACACA
 807
CAGCAGGCCCTCAAG
 808
GTCCAGGTGGATGTGAAAGATCCCCAGCAGG









GAGCT

CCCTC





EREG
NM_001432
 809
TGCTAGGGTAAAC
 810
TGGAGACAAGTCCTG
 811
TAAGCCATGGCTGAC
 812
TGCTAGGGTAAACGAAGGCATAATAAGCCAT









CTCTG

GGCTG





ERG
NM_004449
 813
CCAACACTAGGCT
 814
CCTCCGCCAGGTCTTT
 815
AGCCATATGCCTTCT
 816
CCAACACTAGGCTCCCCACCAGCCATATGCC









CATCT

TTCTCA





ESR1
NM_000125
 817
CGTGGTGCCCCTC
 818
GGCTAGTGGGCGCAT
 819
CTGGAGATGCTGGAC
 820
CGTGGTGCCCCTCTATGACCTGCTGCTGGAG









GCCC

ATGCTG





ESR2
NM_001437
 821
TGGTCCATCGCCAGTTATCA
 822
TGTTCTAGCGATCTTGCTTCACA
 823
ATCTGTATGCGGAAC
 824
TGGTCCATCGCCAGTTATCACATCTGTATGC









CTCAAAAGAGTCCCT

GGAACCTCAAAAGAGTCCCTGGTGTGAAGCA











AGATCGCTAGA





ETV1
NM_004956
 825
TCAAACAAGAGCC
 826
AACTGCCAGAGCTGA
 827
ATCGGGAAGGACCCA
 828
TCAAACAAGAGCCAGGAATGTATCGGGAAGG









CATAC

ACCCA





ETV4
NM_001986
 829
TCCAGTGCCTATG
 830
ACTGTCCAAGGGCAC
 831
CAGACAAATCGCCAT
 832
TCCAGTGCCTATGACCCCCCCAGACAAATCG









CAAGT

CCATCA





EZH2
NM_004456
 833
TGGAAACAGCGAAGGATACA
 834
CACCGAACACTCCCTAGTCC
 835
TCCTGACTTCTGTGA
 836
TGGAAACAGCGAAGGATACAGCCTGTGCACA









GCTCATTGCG

TCCTGACTTCTGTGAGCTCATTGCGCGGGAC











TAGGGAGTGTT





F2R
NM_001992
 837
AAGGAGCAAACCA
 838
GCAGGGTTTCATTGA
 839
CCCGGGCTCAACATC
 840
AAGGAGCAAACCATCCAGGTGCCCGGGCTCA









ACTA

ACATC





FAAH
NM_001441
 841
GACAGCGTAGTGGTGCATGT
 842
AGCTGAACATGGACTGTGGA
 843
TGCCCTTCGTGCACA
 844
GACAGCGTAGTGGTGCATGTGCTGAAGCTGC









CCAATG

AGGGTGCCGTGCCCTTCGTGCACACCAATGT











TCCACAGTCCA





FABP5
NM_001444
 845
GCTGATGGCAGAAAAACTCA
 846
CTTTCCTTCCCATCCCACT
 847
CCTGATGCTGAACCA
 848
GCTGATGGCAGAAAAACTCAGACTGTCTGCA









ATGCACCAT

ACTTTACAGATGGTGCATTGGTTCAGCATCA











GGAGTGGGAT





FADD
NM_003824
 849
GTTTTCGCGAGAT
 850
CTCCGGTGCCTGATTC
 851
AACGCGCTCTTGTCG
 852
GTTTTCGCGAGATAACGGTCGAAAACGCGCT









ATTTC

CTTGTC





FAM107
NM_007177
 853
AAGTCAGGGAAAA
 854
GCTGGCCCTACAGCT
 855
AATTGCCACACTGAC
 856
AAGTCAGGGAAAACCTGCGGAGAATTGCCAC









CAGCG

ACTGA





FAM13C
NM_198215
 857
ATCTTCAAAGCGG
 858
GCTGGATACCACATG
 859
TCCTGACTTTCTCCG
 860
ATCTTCAAAGCGGAGAGCGGGAGGAGCCACG









TGGCT

GAGAA





FAM171B
NM_177454
 861
CCAGGAAGGAAAAGCACTGT
 862
GTGGTCTGCCCCTTCTTTTA
 863
TGAAGATTTTGAAGC
 864
CCAGGAAGGAAAAGCACTGTTGAAGATTTTG









TAATACATCCCCCAC

AAGCTAATACATCCCCCACTAAAAGAAGGGG











CAGACCAC





FAM49B
NM_016623
 865
AGATGCAGAAGGC
 866
GCTGGATTGCCTCT
 867
TGGCCAGCTCCTCTG
 868
AGATGCAGAAGGCATCTTGGAGGACTTGCAG









TATGA

TCATA





FAM73A
NM_198549
 869
TGAGAAGGTGCGCTATTCAA
 870
GGCCATTAAAAGCTCAGTGC
 871
AAGACCTCATGCAGT
 872
TGAGAAGGTGCGCTATTCAAGTACAGAGACT









TACTCATTCGCC

TTAGCTGAAGACCTCATGCAGTTACTCATTC











GCCGCACTGAG





FAP
NM_004460
 873
GTTGGCTCACGTG
 874
GACAGGACCGAAACA
 875
AGCCACTGCAAACAT
 876
GTTGGCTCACGTGGGTTACTGATGAACGAGT









ACTCG

ATGTTT





FAS
NM_000043
 877
GGATTGCTCAACAACCATGCT
 878
GGCATTAACACTTTTGGACGATAA
 879
TCTGGACCCTCCTAC
 880
GGATTGCTCAACAACCATGCTGGGCATCTGG









CTCTGGTTCTTACGT

ACCCTCCTACCTCTGGTTCTTACGTCTGTTG











CTAGATTATCG





FASLG
NM_000639
 881
GCACTTTGGGATTCTTTCCATTAT
 882
GCATGTAAGAAGACCCTCACTGAA
 883
ACAACATTCTCGGTG
 884
GCACTTTGGGATTCTTTCCATTATGATTCTT









CCTGTAACAAAGAA

TGTTACAGGCACCGAGAATGTTGTATTCAGT











GAGGGTCTTCTT





FASN
NM_004104
 885
GCCTCTTCCTGTTC
 886
GCTTTGCCCGGTAGC
 887
TCGCCCACCTACGTA
 888
GCCTCTTCCTGTTCGACGGCTCGCCCACCTA









CTGGC

CGTACT





FCGR3A
NM_000569
 889
GTCTCCAGTGGAA
 890
AGGAATGCAGCTACT
 891
CCCATGATCTTCAAG
 892
GTCTCCAGTGGAAGGGAAAAGCCCATGATCT









CAGGG

TCAAG





FGF10
NM_004465
 893
TCTTCCGTCCCTGT
 894
AGAGTTGGTGGCCTC
 895
ACACCATGTCCTGAC
 896
TCTTCCGTCCCTGTCACCTGCCAAGCCCTTG









CAAGG

GTCAGG





FGF17
NM_003867
 897
GGTGGCTGTCCTC
 898
TCTAGCCAGGAGGAG
 899
TTCTCGGATCTCCCT
 900
GGTGGCTGTCCTCAAAATCTGCTTCTCGGAT









CAGTC

CTCCCT





FGF5
NM_004464
 901
GCATCGGTTTCCA
 902
AACATATTGGCTTCGT
 903
CCATTGACTTTGCCA
 904
GCATCGGTTTCCATCTGCAGATCTACCCGGA









TCCGG

TGGCAA





FGF6
NM_020996
 905
GGGCCATTAATTCTGACCAC
 906
CCCGGGACATAGTGATGAA
 907
CATCCACCTTGCCTC
 908
GGGCCATTAATTCTGACCACGTGCCTGAGAG









TCAGGCAC

GCAAGGTGGATGGCCCTGGGACAGAAACTGT











TCATCACTAT





FGF7
NM_002009
 909
CCAGAGCAAATGGCTACAAA
 910
TCCCCTCCTTCCATGTAATC
 911
CAGCCCTGAGCGACA
 912
CCAGAGCAAATGGCTACAAATGTGAACTGTT









CACAAGAAG

CCAGCCCTGAGCGACACACAAGAAGTTATGA











TTACATGGAA





FGFR2
NM_000141
 913
GAGGGACTGTTGGCATGCA
 914
GAGTGAGAATTCGATCCAAGTCTT
 915
TCCCAGAGACCAACG
 916
GAGGGACTGTTGGCATGCAGTGCCCTCCCAG







C

TTCAAGCAGTTG

AGACCAACGTTCAAGCAGTTGGTAGAAGACT











TGGATCGAAT





FGFR4
NM_002011
 917
CTGGCTTAAGGATGGACAGG
 918
ACGAGACTCCAGTGCTGATG
 919
CCTTTCATGGGGAGA
 920
CTGGCTTAAGGATGGACAGGCCTTTCATGGG









ACCGCATT

GAGAACCGCATTGGAGGCATTCGGCTGCGCC











ATCAGCACTG





FKBP5
NM_004117
 921
CCCACAGTAGAGG
 922
GGTTCTGGCTTTCACG
 923
TCTCCCCAGTTCCAC
 924
CCCACAGTAGAGGGGTCTCATGTCTCCCCAG









AGCAG

TTCCAC





FLNA
NM_001456
 925
GAACCTGCGGTGG
 926
GAAGACACCCTGGCC
 927
TACCAGGCCCATAGC
 928
GAACCTGCGGTGGACACTTCCGGTGTCCAGT









ACTGG

GCTAT





FLNC
NM_001458
 929
CAGGACAATGGTG
 930
TGATGGTGTACTCGC
 931
ATGTGCTGTCAGCTA
 932
CAGGACAATGGTGATGGCTCATGTGCTGTCA









CCTGC

GCTAC





FLT1
NM_002019
 933
GGCTCCTGAATCT
 934
TCCCACAGCAATACT
 935
CTACAGCACCAAGAG
 936
GGCTCCTGAATCTATCTTTGACAAAATCTAC









CGAC

AGCACC





FLT4
NM_002020
 937
ACCAAGAAGCTGA
 938
CCTGGAAGCTGTAGC
 939
AGCCCGCTGACCATG
 940
ACCAAGAAGCTGAGGACCTGTGGCTGAGCCC









GAAGA

GCTGA





FN1
NM_002026
 941
GGAAGTGACAGAC
 942
ACACGGTAGCCGGTC
 943
ACTCTCAGGCGGTGT
 944
GGAAGTGACAGACGTGAAGGTCACCATCATG









CCACA

TGGAC





FOS
NM_005252
 945
CGAGCCCTTTGATGACTTCCT
 946
GGAGCGGGCTGTCTCAGA
 947
TCCCAGCATCATCCA
 948
CGAGCCCTTTGATGACTTCCTGTTCCCAGCA









GGCCCAG

TCATCCAGGCCCAGTGGCTCTGAGACAGCCC











GCTCC





FOXO1
NM_002015
 949
GTAAGCACCATGC
 950
GGGGCAGAGGCACTT
 951
TATGAACCGCCTGAC
 952
GTAAGCACCATGCCCCACACCTCGGGTATGA









CCAAG

ACCGC





FOXP3
NM_014009
 953
CTGTTTGCTGTCCG
 954
GTGGAGGAACTCTGG
 955
TGTTTCCATGGCTAC
 956
CTGTTTGCTGTCCGGAGGCACCTGTGGGGTA









CCCAC

GCCAT





FOXQ1
NM_033260
 957
TGTTTTTGTCGCAA
 958
TGGAAAGGTTCCCTG
 959
TGATTTATGTCCCTT
 960
TGTTTTTGTCGCAACTTCCATTGATTTATGT









CCCTC

CCCTTCC





FSD1
NM_024333
 961
AGGCCTCCTGTCC
 962
TGTGTGAACCTGGTC
 963
CGCACCAAACAAGTG
 964
AGGCCTCCTGTCCTTCTACAATGCCCGCACC









CTGCA

AAACAA





FYN
NM_002037
 965
GAAGCGCAGATCA
 966
CTCCTCAGACACCAC
 967
CTGAAGCACGACAAG
 968
GAAGCGCAGATCATGAAGAAGCTGAAGCACG









CTGGT

ACAAG





G6PD
NM_000402
 969
AATCTGCCTGTGG
 970
CGAGATGTTGCTGGT
 971
CCAGCCTCAGTGCCA
 972
AATCTGCCTGTGGCCTTGCCCGCCAGCCTCA









CTTGA

GTGCCA





GABRG2
NM_198904
 973
CCACTGTCCTGACAATGACC
 974
GAGATCCATCGCTGTGACAT
 975
CTCAGCACCATTGCC
 976
CCACTGTCCTGACAATGACCACCCTCAGCAC









CGGAAAT

CATTGCCCGGAAATCGCTCCCCAAGGTCTCC











TATGTCACAGC





GADD45
NM_001924
 977
GTGCTGGTGACGA
 978
CCCGGCAAAAACAAA
 979
TTCATCTCAATGGAA
 980
GTGCTGGTGACGAATCCACATTCATCTCAAT









GGATC

GGAAG





GADD45
NM_015675
 981
ACCCTCGACAAGA
 982
TGGGAGTTCATGGGT
 983
TGGGAGTTCATGGGT
 984
ACCCTCGACAAGACCACACTTTGGGACTTGG









ACAGA

GAGCT





GDF15
NM_004864
 985
CGCTCCAGACCTA
 986
ACAGTGGAAGGACCA
 987
TGTTAGCCAAAGACT
 988
CGCTCCAGACCTATGATGACTTGTTAGCCAA









GCCAC

AGACTG





GHR
NM_000163
 989
CCACCTCCCACAG
 990
GGTGCGTGCCTGTAG
 991
CGTGCCTCAGCCTCC
 992
CCACCTCCCACAGGTTCAGGCGATTCCCGTG









TGAGT

CCTCAG





GNPTAB
NM_024312
 993
GGATTCACATCGC
 994
GTTCTTGCATAACAAT
 995
CCCTGCTCACATGCC
 996
GGATTCACATCGCGGAAAGTCCCTGCTCACA









TCACA

TGCCTC





GNRH1
NM_000825
 997
AAGGGCTAAATCCAGGTGTG
 998
CTGGATCTCTGTGGCTGGT
 999
TCCTGTCCTTCACTG
1000
AAGGGCTAAATCCAGGTGTGACGGTATCTAA









TCCTTGCCA

TGATGTCCTGTCCTTCACTGTCCTTGCCATC











ACCAGCCACAG





GPM6B
NM_001001994
1001
ATGTGCTTGGAGTGGCCT
1002
TGTAGAACATAAACACGGGCA
1003
CGCTGAGAAACCAAA
1004
ATGTGCTTGGAGTGGCCTGGCTGGGTGTGTT









CACACCCAG

TGGTTTCTCAGCGGTGCCCGTGTTTATGTTC











TACA





GPNMB
NM_001005340
1005
CAGCCTCGCCTTTAAGGAT
1006
TGACAAATATGGCCAAGCAG
1007
CAAACAGTGCCCTGA
1008
CAGCCTCGCCTTTAAGGATGGCAAACAGTGC









TCTCCGTTG

CCTGATCTCCGTTGGCTGCTTGGCCATATTT











GTCA





GPR68
NM_003485
1009
CAAGGACCAGATC
1010
GGTAGGGCAGGAAGC
1011
CTCAGCACCGTGGTC
1012
CAAGGACCAGATCCAGCGGCTGGTGCTCAGC









ATCTT

ACCGT





GPS1
NM_004127
1013
AGTACAAGCAGGC
1014
GCAGCTCAGGGAAGT
1015
CCTCCTGCTGGCTTC
1016
AGTACAAGCAGGCTGCCAAGTGCCTCCTGCT









CTTTG

GGCTT





GRB7
NM_005310
1017
CCATCTGCATCCA
1018
GGCCACCAGGGTATT
1019
CTCCCCACCCTTGAG
1020
CCATCTGCATCCATCTTGTTTGGGCTCCCCA









AAGTG

CCCTTG





GREM1
NM_013372
1021
GTGTGGGCAAGGA
1022
GACCTGATTTGGCCT
1023
TCCACCCTCCCTTTC
1024
GTGTGGGCAAGGACAAGCAGGATAGTGGAGT









TCACT

GAGAA





GSK3B
NM_002093
1025
GACAAGGACGGCA
1026
TTGTGGCCTGTCTGG
1027
CCAGGAGTTGCCACC
1028
GACAAGGACGGCAGCAAGGTGACAACAGTGG









ACTGT

TGGCA





GSN
NM_000177
1029
CTTCTGCTAAGCGGTACATCGA
1030
GGCTCAAAGCCTTGCTTCAC
1031
ACCCAGCCAATCGGG
1032
CTTCTGCTAAGCGGTACATCGAGACGGACCC









ATCGGC

AGCCAATCGGGATCGGCGGACGCCCATCACC











GTGGTGAAGC





GSTM1
NM_000561
1033
AAGCTATGAGGAAAAGAAGTACAC
1034
GGCCCAGCTTGAATTTTTCA
1035
TCAGCCACTGGCTTC
1036
AAGCTATGAGGAAAAGAAGTACACGATGGGG





GA



TGTCATAATCAGGAG

GACGCTCCTGATTATGACAGAAGCCAGTGGC











TGAATGAAAA





GSTM2
NM_000848
1037
CTGCAGGCACTCC
1038
CCAAGAAACCATGGC
1039
CTGAAGCTCTACTCA
1040
CTGCAGGCACTCCCTGAAATGCTGAAGCTCT









CAGTT

ACTCAC





HDAC1
NM_004964
1041
CAAGTACCACAGCGATGACTACAT
1042
GCTTGCTGTACTCCGACATGTT
1043
TTCTTGCGCTCCATC
1044
CAAGTACCACAGCGATGACTACATTAAATTC





TA



CGTCCAGA

TTGCGCTCCATCCGTCCAGATAACATGTCGG











AGTACAGCAAG





HDAC9
NM_178423
1045
AACCAGGCAGTCACCTTGAG
1046
CTCTGTCTTCCTGCATCGC
1047
CCCCCTGAAGCTCTT
1048
AACCAGGCAGTCACCTTGAGGAAGCAGAGGA









CCTCTGCTT

AGAGCTTCAGGGGGACCAGGCGATGCAGGAA











GACAGAG





HGD
NM_000187
1049
CTCAGGTCTGCCC
1050
TTATTGGTGCTCCGTG
1051
CTGAGCAGCTCTCAG
1052
CTCAGGTCTGCCCCTACAATCTCTATGCTGA









GATCG

GCAGCT





HIP1
NM_005338
1053
CTCAGAGCCCCAC
1054
GGGTTTCCCTGCCAT
1055
CGACTCACTGACCGA
1056
CTCAGAGCCCCACCTGAGCCTGCCGACTCAC









GGCCT

TGACC





HIRIP3
NM_003609
1057
GGATGAGGAAAAG
1058
TCCCTAGCTGACTTTC
1059
CCATTGCTCCTGGTT
1060
GGATGAGGAAAAGGGGGATTGGAAACCCAGA









CTGGG

ACCAG





HK1
NM_000188
1061
TACGCACAGAGG
1062
GAGAGAGTGCTGGA
1063
TAAGAGTCCGGGATC
1064
TACGCACAGAGGCAAGCAGCTAAGAGTCCGG









CCCAG

GATCC





HLA-G
NM_002127
1065
CCATCCCCATCAT
1066
CCGCAGCTCCAGTGA
1067
CTGCAAGGACAACCA
1068
CCTGCGCGGCTACTACAACCAGAGCGAGGCC









GGCC

AGTTC





HLF
NM_002126
1069
CACCCTGCAGGTG
1070
GGTACCTAGGAGCAG
1071
TAAGTGATCTGCCCT
1072
CACCCTGCAGGTGTCTGAGACTAAGTGATCT









CCAGG

GCCCTC





HNF1B
NM_000458
1073
TCCCAGCATCTCA
1074
CGTACCAGGTGTACA
1075
CCCCTATGAAGACCC
1076
TCCCAGCATCTCAACAAGGGCACCCCTATGA









AGAAG

AGACC





HPS1
NM_000195
1077
GCGGAAGCTGTAT
1078
TTCGGATAAGATGAC
1079
CAGTCACCAGCCCAA
1080
GCGGAAGCTGTATGTGCTCAAGTACCTGTTT









AGTGC

GAAGT





HRAS
NM_005343
1081
GGACGAATACGAC
1082
GCACGTCTCCCCATC
1083
ACCACCTGCTTCCGG
1084
GGACGAATACGACCCCACTATAGAGGATTCC









TAGGA

TACCG





HSD17B10
NM_004493
1085
CCAGCGAGTTCTTGATGTGA
1086
ATCTCACCAGCCACCAGG
1087
TCATGGGCACCTTCA
1088
CCACCAGACAAGACCGATTCGCTGGCCTCCA









ATGTGATCC

TTTCTTCAACCCAGTGCCTGTCATGAAACTT











GTGG





HSD17B2
NM_002153
1089
GCTTTCCAAGTGG
1090
TGCCTGCGATATTTGT
1091
AGTTGCTTCCATCCA
1092
GCTTTCCAAGTGGGGAATTAAAGTTGCTTCC









ACCTG

ATCCAA





HSD17B3
NM_000197
1093
GGGACGTCCTGGAACAGT
1094
TGGAGAATCTCACGCACTTC
1095
CTTCATCCTCACAGG
1096
GGGACGTCCTGGAACAGTTCTTCATCCTCAC









GCTGCTGGT

AGGGCTGCTGGTGTGCCTGGCCTGCCTGGCG











AAGTGCGTGAG





HSD17B4
NM_000414
1097
CGGGAAGCTTCAG
1098
ACCTCAGGCCCAATA
1099
AGGCGGCGTCCTATT
1100
CGGGAAGCTTCAGAGTACCTTTGTATTTGAG









TCCTC

GAAAT





HSD3B2
NM_000198
1101
GCCTTCCTTTAACC
1102
GGAGTAAATTGGGCT
1103
ACTTCCAGCAGGAAG
1104
GCCTTCCTTTAACCCTGATGTACTGGATTGG









CCAAT

CTTCCT





HSP90AB1
NM_007355
1105
GCATTGTGACCAGCACCTA
1106
GAAGTGCCTGGGCTTTCAT
1107
ATCCGCTCCATATTG
1108
GCATTGTGACCAGCACCTACGGCTGGACAGC









GCTGTCCAG

CAATATGGAGCGGATCATGAAAGCCCAGGCA











CTTC





HSPA5
NM_005347
1109
GGCTAGTAGAACTGGATCCCAACA
1110
GGTCTGCCCAAATGCTTTTC
1111
TAATTAGACCTAGGC
1112
GGCTAGTAGAACTGGATCCCAACACCAAAAC









CTCAGCTGCACTGCC

TCTTAATTAGACCTAGGCCTCAGCTGCACTG











CCCGAAAAGCA





HSPA8
NM_006597
1113
CCTCCCTCTGGTGGTGCTT
1114
GCTACATCTACACTTGGTTGGCTT
1115
CTCAGGGCCCACCAT
1116
CCTCCCTCTGGTGGTGCTTCCTCAGGGCCCA







AA

TGAAGAGGTTG

CCATTGAAGAGGTTGATTAAGCCAACCAAGT











GTAGATGTAGC





HSPB1
NM_001540
1117
CCGACTGGAGGAGCATAAA
1118
ATGCTGGCTGACTCTGCTC
1119
CGCACTTTTCTGAGC
1120
CCGACTGGAGGAGCATAAAAGCGCAGCCGAG









AGACGTCCA

CCCAGCGCCCCGCACTTTTCTGAGCAGACGT











CCAGAGCAGA





HSPB2
NM_001541
1121
CACCACTCCAGAG
1122
TGGGACCAAACCATA
1123
CACCTTTCCCTTCCC
1124
CACCACTCCAGAGGTAGCAGCATCCTTGGGG









CCAAG

GAAGG





HSPE1
NM_002157
1125
GCAAGCAACAGTAGTCGCTG
1126
CCAACTTTCACGCTAACTGGT
1127
TCTCCACCCTTTCCT
1128
GCAAGCAACAGTAGTCGCTGTTGGATCGGGT









TTAGAACCCG

TCTAAAGGAAAGGGTGGAGAGATTCAACCAG











TTAGCGTGAA





HSPG2
NM_005529
1129
GAGTACGTGTGCC
1130
CTCAATGGTGACCAG
1131
CAGCTCCGTGCCTCT
1132
GAGTACGTGTGCCGAGTGTTGGGCAGCTCCG









AGAGG

TGCCT





ICAM1
NM_000201
1133
GCAGACAGTGACCATCTACAGCTT
1134
CTTCTGAGACCTCTGGCTTCGT
1135
CCGGCGCCCAACGTG
1136
GCAGACAGTGACCATCTACAGCTTTCCGGCG









ATTCT

CCCAACGTGATTCTGACGAAGCCAGAGGTCT











CAGAAG





IER3
NM_003897
1137
GTACCTGGTGCGCGAGAG
1138
GCGTCTCCGCTGTAGTGTT
1139
TCAAGTTGCCTCGGA
1140
GTACCTGGTGCGCGAGAGCGTATCCCCAACT









AGTCCCAGT

GGGACTTCCGAGGCAACTTGAACTCAGAACA











CTACAGCGGA





IFI30
NM_006332
1141
ATCCCATGAAGCC
1142
GCACCATTCTTAGTG
1143
AAAATTCCACCCCAT
1144
ATCCCATGAAGCCCAGATACACAAAATTCCA









GATCA

CCCCA





IFIT1
NM_001548
1145
TGACAACCAAGCA
1146
CAGTCTGCCCATGTG
1147
AAGTTGCCCCAGGTC
1148
TGACAACCAAGCAAATGTGAGGAGTCTGGTG









ACCAG

ACCTG





IFNG
NM_000619
1149
GCTAAAACAGGGAAGCGAAA
1150
CAACCATTACTGGGATGCTC
1151
TCGACCTCGAAACAG
1152
GCTAAAACAGGGAAGCGAAAAAGGAGTCAGA









CATCTGACTCC

TGCTTTTCGAGGTCGAAGAGCATCCCAGTAA











TGGTTG





IGF1
NM_000618
1153
TCCGGAGCTGTGA
1154
CGGACAGAGCGAGCT
1155
TGTATTGCGCACCCC
1156
TCCGGAGCTGTGATCTAAGGAGGCTGGAGAT









TCAAG

GTATT





IGF1R
NM_000875
1157
GCATGGTAGCCGAAGATTTCA
1158
TTTCCGGTAATAGTCTGTCTCATA
1159
CGCGTCATACCAAAA
1160
GCATGGTAGCCGAAGATTTCACAGTCAAAAT







GATATC

TCTCCGATTTTGA

CGGAGATTTTGGTATGACGCGAGATATCTAT











GAGACAGACTA





IGF2
NM_000612
1161
CCGTGCTTCCGGAA
1162
TGGACTGCTTCCAGG
1163
TACCCCGTGGGCAAG
1164
CCGTGCTTCCGGACAACTTCCCCAGATACCC









TTCTT

CGTGGG





IGFBP2
NM_000597
1165
GTGGACAGCACCA
1166
CCTTCATACCCGACTT
1167
CTTCCGGCCAGCACT
1168
GTGGACAGCACCATGAACATGTTGGGCGGGG









GCCTC

GAGGC





IGFBP3
NM_000598
1169
ACATCCCAACGCA
1170
CCACGCCCTTGTTTCA
1171
ACACCACAGAAGGCT
1172
ACATCCCAACGCATGCTCCTGGAGCTCACAG









GTGA

CCTTCT





IGFBP5
NM_000599
1173
TGGACAAGTACGG
1174
CGAAGGTGTGGCACT
1175
CCCGTCAACGTACTC
1176
TGGACAAGTACGGGATGAAGCTGCCAGGCAT









CATGC

GGAGT





IGFBP6
NM_002178
1177
TGAACCGCAGAGACCAACAG
1178
GTCTTGGACACCCGCAGAAT
1179
ATCCAGGCACCTCTA
1180
TGAACCGCAGAGACCAACAGAGGAATCCAGG









CCACGCCCTC

CACCTCTACCACGCCCTCCCAGCCCAATTCT











GCGGGTGTCCA





IL10
NM_000572
1181
CTGACCACGCTTT
1182
CCAAGCCCAGAGACA
1183
TTGAGCTGTTTTCCC
1184
CTGACCACGCTTTCTAGCTGTTGAGCTGTTT









TGACC

TCCCTG





IL11
NM_000641
1185
TGGAAGGTTCCAC
1186
TCTTGACCTTGCAGCT
1187
CCTGTGATCAACAGT
1188
TGGAAGGTTCCACAAGTCACCCTGTGATCAA









ACCCG

CAGTA





IL17A
NM_002190
1189
TCAAGCAACACTC
1190
CAGCTCCTTTCTGGGT
1191
TGGCTTCTGTCTGAT
1192
TCAAGCAACACTCCTAGGGCCTGGCTTCTGT









CAAGG

CTGATC





IL1A
NM_000575
1193
GGTCCTTGGTAGA
1194
GGATGGAGCTTCAGG
1195
TCTCCACCCTGGCCC
1196
GGTCCTTGGTAGAGGGCTACTTTACTGTAAC









TGTTA

AGGGC





IL1B
NM_000576
1197
AGCTGAGGAAGAT
1198
GGAAAGAAGGTGCTC
1199
TGCCCACAGACCTTC
1200
AGCTGAGGAAGATGCTGGTTCCCTGCCCACA









CAGGA

GACCT





IL2
NM_000586
1201
ACCTCAACTCCTGCCACAAT
1202
CACTGTTTGTGACAAGTGCAAG
1203
TGCAACTCCTGTCTT
1204
ACCTCAACTCCTGCCACAATGTACAGGATGC









GCATTGCAC

AACTCCTGTCTTGCATTGCACTAAGTCTTGC











ACTTGTCACAAA





IL6
NM_000600
1205
CCTGAACCTTCCA
1206
ACCAGGCAAGTCTCC
1207
CCAGATTGGAAGCAT
1208
CCTGAACCTTCCAAAGATGGCTGAAAAAGAT









CCATC

GGATG





IL6R
NM_000565
1209
CCAGCTTATCTCA
1210
CTGGCGTAGAACCTT
1211
CCTTTGGCTTCACGG
1212
CCAGCTTATCTCAGGGGTGTGCGGCCTTTGG









AAGAG

CTTCAC





IL6ST
NM_002184
1213
GGCCTAATGTTCC
1214
AAAATTGTGCCTTGG
1215
CATATTGCCCAGTGG
1216
GGCCTAATGTTCCAGATCCTTCAAAGAGTCA









TCACC

TATTGC





IL8
NM_000584
1217
AAGGAACCATCTCACTGTGTGTAA
1218
ATCAGGAAGGCTGCCAAGAG
1219
TGACTTCCAAGCTGG
1220
AAGGAACCATCTCACTGTGTGTAAACATGAC





AC



CCGTGGC

TTCCAAGCTGGCCGTGGCTCTCTTGGCAGCC











TTCCTGAT





ILF3
NM_004516
1221
GACACGCCAAGTG
1222
CTCAAGACCCGGATC
1223
ACACAAGACTTCAGC
1224
GACACGCCAAGTGGTTCCAGGCCAGAGCCAA









CCGTT

CGGGC





ILK
NM_001014794
1225
CTCAGGATTTTCTCGCATCC
1226
AGGAGCAGGTGGAGACTGG
1227
ATGTGCTCCCAGTGC
1228
CTCAGGATTTTCTCGCATCCAAATGTGCTCC









TAGGTGCCT

CAGTGCTAGGTGCCTGCCAGTCTCCACCTGC











TCCT





IMMT
NM_006839
1229
CTGCCTATGCCAG
1230
GCTTTTCTGGCTTCCT
1231
CAACTGCATGGCTCT
1232
CTGCCTATGCCAGACTCAGAGGAATCGAACA









GAACA

GGCTG





ING5
NM_032329
1233
CCTACAGCAAGTG
1234
CATCTCGTAGGTCTG
1235
CCAGCTGCACTTTGT
1236
CCTACAGCAAGTGCAAGGAATACAGTGACGA









CGTCA

CAAAG





INHBA
NM_002192
1237
GTGCCCGAGCCAT
1238
CGGTAGTGGTTGATG
1239
ACGTCCGGGTCCTCA
1240
GTGCCCGAGCCATATAGCAGGCACGTCCGGG









CTGTC

TCCTC





INSL4
NM_002195
1241
CTGTCATATTGCCC
1242
CAGATTCCAGCAGCC
1243
TGAGAAGACATTCAC
1244
CTGTCATATTGCCCCATGCCTGAGAAGACAT









CACCA

TCACCA





ITGA1
NM_181501
1245
GCTTCTTCTGGAG
1246
CCTGTAGATAATGAC
1247
TTGCTGGACAGCCTC
1248
GCTTCTTCTGGAGATGTGCTCTATATTGCTG









GGTAC

GACAGC





ITGA3
NM_002204
1249
CCATGATCCTCAC
1250
GAAGCTTTGTAGCCG
1251
CACTCCAGACCTCGC
1252
CCATGATCCTCACTCTGCTGGTGGACTATAC









TTAGC

ACTCCA





ITGA4
NM_000885
1253
CAACGCTTCAGTG
1254
GTCTGGCCGGGATTC
1255
CGATCCTGCATCTGT
1256
CAACGCTTCAGTGATCAATCCCGGGGCGATT









AAATC

TACAG





ITGA5
NM_002205
1257
AGGCCAGCCCTAC
1258
GTCTTCTCCACAGTCC
1259
TCTGAGCCTTGTCCT
1260
AGGCCAGCCCTACATTATCAGAGCAAGAGCC









CTATC

GGATA





ITGA6
NM_000210
1261
CAGTGACAAACAG
1262
GTTTAGCCTCATGGG
1263
TCGCCATCTTTTGTG
1264
CAGTGACAAACAGCCCTTCCAACCCAAGGAA









GGATT

TCCCA





ITGA7
NM_002206
1265
GATATGATTGGTCGCTGCTTTG
1266
AGAACTTCCATTCCCCACCAT
1267
CAGCCAGGACCTGGC
1268
GATATGATTGGTCGCTGCTTTGTGCTCAGCC









CATCCG

AGGACCTGGCCATCCGGGATGAGTTGGATGG











TGGGGAATGGA





ITGAD
NM_005353
1269
GAGCCTGGTGGAT
1270
ACTGTCAGGATGCCC
1271
CAACTGAAAGGCCTG
1272
GAGCCTGGTGGATCCCATCGTCCAACTGAAA









ACGTT

GGCCT





ITGB3
NM_000212
1273
ACCGGGAGCCCTACATGAC
1274
CCTTAAGCTCTTTCACTGACTCAA
1275
AAATACCTGCAACCG
1276
ACCGGGGAGCCCTACATGACGAAAATACCTG







TCT

TTACTGCCGTGAC

CAACCGTTACTGCCGTGACGAGATTGAGTCA











GTGAAAGAGC





ITGB4
NM_000213
1277
CAAGGTGCCCTCA
1278
GCGCACACCTTCATC
1279
CACCAACCTGTACCC
1280
CAAGGTGCCCTCAGTGGAGCTCACCAACCTG









GTATT

TACCC





ITGB5
NM_002213
1281
TCGTGAAAGATGA
1282
GGTGAACATCATGAC
1283
TGCTATGTTTCTACA
1284
TCGTGAAAGATGACCAGGAGGCTGTGCTATG









AAACC

TTTCTA





ITPR1
NM_002222
1285
GAGGAGGTGTGGG
1286
GTAATCCCATGTCCG
1287
CCATCCTAACGGAAC
1288
GAGGAGGTGTGGGTGTTCCGCTTCCATCCTA









GAGCT

ACGGA





ITPR3
NM_002224
1289
TTGCCATCGTGTC
1290
ATGGAGCTGGCGTCA
1291
TCCAGGTCTCGGATC
1292
TTGCCATCGTGTCAGTGCCCGTGTCTGAGAT









TCAGA

CCGAGA





ITSN1
NM_003024
1293
TAACTGGGATGCA
1294
CTCTGCCTTAACTGGC
1295
AGCCCTCTCTCACCG
1296
TAACTGGGATGCATGGGCAGCCCAGCCCTCT









TTCCA

CTCAC





JAG1
NM_000214
1297
TGGCTTACACTGG
1298
GCATAGCTGTGAGAT
1299
ACTCGATTTCCCAGC
1300
TGGCTTACACTGGCAATGGTAGTTTCTGTGG









CAACC

TTGGCT





JUN
NM_002228
1301
GACTGCAAAGATGGAAACGA
1302
TAGCCATAAGGTCCGCTCTC
1303
CTATGACGATGCCCT
1304
GACTGCAAAGATGGAAACGACCTTCTATGAC









CAACGCCTC

GATGCCCTCAACGCCTCGTTCCTCCCGTCCG











AGAGCGGACCT





JUNB
NM_002229
1305
CTGTCAGCTGCTG
1306
AGGGGGTGTCCGTAA
1307
CAAGGGACACGCCTT
1308
CTGTCAGCTGCTGCTTGGGGTCAAGGGACAC









CTGAA

GCCTT





KCNN2
NM_021614
1309
TGTGCTATTCATCC
1310
GGGCATAGGAGAAGG
1311
TTATACATTCACATG
1312
TGTGCTATTCATCCCATACCTGGGAATTATA









GACGG

CATTCA





KCTD12
NM_138444
1313
AGCAGTTACTGGC
1314
TGGAGACCTGAGCAG
1315
ACTCTTAGGCGGCAG
1316
AGCAGTTACTGGCAAGAGGGAGAAAGGACGC









CGTCC

TGCCG





KHDRBS
NM_006558
1317
CGGGCAAGAAGAG
1318
CTGTAGACGCCCTTT
1319
CAAGACACAAGGCAC
1320
CGGGCAAGAAGAGTGGACTAACTCAAGACAC









CTTCA

AAGGC





KIAA019
NM_014846
1321
CAGACACCAGCTC
1322
AACATTGTGAGGCGG
1323
TCCCCAGTGTCCAGG
1324
CAGACACCAGCTCTGAGGCCAGTTAATCATC









CACAG

CCCAG





KIAA024
NM_014734
1325
CCGTGGGACATGG
1326
GAAGCAAGTCCGTCT
1327
TCCGCTAGTGATCCT
1328
CCGTGGGACATGGAGTGTTCCTTCCGCTAGT









TTGCA

GATCCT





KIF4A
NM_012310
1329
AGAGCTGGTCTCC
1330
GCTGGTCTTGCTCTGT
1331
CAGGTCAGCAAACTT
1332
AGAGCTGGTCTCCTCCAAAATACAGGTCAGC









GAAAG

AAACT





KIT
NM_000222
1333
GAGGCAACTGCTTATGGCTTAATT
1334
GGCACTCGGCTTGAGCAT
1335
TTACAGCGACAGTCA
1336
GAGGCAACTGCTTATGGCTTAATTAAGTCAG





A



TGGCCGCAT

ATGCGGCCATGACTGTCGCTGTAAAGATGCT











CAAGCCGAGT





KLC1
NM_182923
1337
AGTGGCTACGGGA
1338
TGAGCCACAGACTGC
1339
CAACACGCAGCAGAA
1340
AGTGGCTACGGGATGAACTGGCCAACACGCA









ACTG

GCAGA





KLF6
NM_001300
1341
CACGAGACCGGCT
1342
GCTCTAGGCAGGTCT
1343
AGTACTCCTCCAGAG
1344
CACGAGACCGGCTACTTCTCGGCGCTGCCGT









ACGGC

CTCTGG





KLK1
NM_002257
1345
AACACAGCCCAGTTTGTTCA
1346
CCAGGAGGCTCATGTTGAAG
1347
TCAGTGAGAGCTTCC
1348
AACACAGCCCAGTTTGTTCATGTCAGTGAGA









CACACCCTG

GCTTCCCACACCCTGGCTTCAACATGAGCCT











CCTGG





KLK10
NM_002776
1349
GCCCAGAGGCTCC
1350
CAGAGGTTTGAACAG
1351
CCTCTTCCTCCCCAG
1352
GCCCAGAGGCTCCATCGTCCATCCTCTTCCT









TCGGC

CCCCAG





KLK11
NM_006853
1353
CACCCCGGCTTCA
1354
CATCTTCACCAGCAT
1355
CCTCCCCAACAAAGA
1356
CACCCCGGCTTCAACAACAGCCTCCCCAACA









CCACC

AAGAC





KLK14
NM_022046
1357
CCCCTAAAATGTT
1358
CTCATCCTCTTGGCTC
1359
CAGCACTTCAAGTCC
1360
CCCCTAAAATGTTCCTCCTGCTGACAGCACT









TGGCT

TCAAGT





KLK2
NM_005551
1361
AGTCTCGGATTGT
1362
TGTACACAGCCACCT
1363
TTGGGAATGCTTCTC
1364
AGTCTCGGATTGTGGGAGGCTGGGAGTGTGA









ACACT

GAAGC





KLK3
NM_001648
1365
CCAAGCTTACCAC
1366
AGGGTGAGGAAGACA
1367
ACCCACATGGTGACA
1368
CCAAGCTTACCACCTGCACCCGGAGAGCTGT









CAGCT

GTCAC





KLRK1
NM_007360
1369
TGAGAGCCAGGCT
1370
ATCCTGGTCCTCTTTG
1371
TGTCTCAAAATGCCA
1372
TGAGAGCCAGGCTTCTTGTATGTCTCAAAAT









GCCTT

GCCAGC





KPNA2
NM_002266
1373
TGATGGTCCAAAT
1374
AAGCTTCACAAGTTG
1375
ACTCCTGTTTTCACC
1376
TGATGGTCCAAATGAACGAATTGGCATGGTG









ACCAT

GTGAA





KRT1
NM_006121
1377
TGGACAACAACCG
1378
TATCCTCGTACTGGG
1379
CCTCAGCAATGATGC
1380
TGGACAACAACCGCAGTCTCGACCTGGACAG









TGTCC

CATCA





KRT15
NM_002275
1381
GCCTGGTTCTTCA
1382
CTTGCTGGTCTGGATC
1383
TGAACAAAGAGGTGG
1384
GCCTGGTTCTTCAGCAAGACTGAGGAGCTGA









CCTCC

ACAAA





KRT18
NM_000224
1385
AGAGATCGAGGCT
1386
GGCCTTTTACTTCCTC
1387
TGGTTCTTCTTCATG
1388
AGAGATCGAGGCTCTCAAGGAGGAGCTGCTC









AAGAG

TTCAT





KRT2
NM_000423
1389
CCAGTGACGCCTC
1390
GGGCATGGCTAGAAG
1391
ACCTAGACAGCACAG
1392
CCAGTGACGCCTCTGTGTTCTGGGGCGGAAT









ATTCC

CTGTGC





KRT5
NM_000424
1393
TCAGTGGAGAAGG
1394
TGCCATATCCAGAGG
1395
CCAGTCAACATCTCT
1396
TCAGTGGAGAAGGAGTTGGACCAGTCAACAT









GTTGT

CTCTG





KRT75
NM_004693
1397
TCAAAGTCAGGTACGAAGATGAAA
1398
ACGTCCTTTTTCAGGGCTACAA
1399
TTCATTCTCAGCAGC
1400
TCAAAGTCAGGTACGAAGATGAAATTAACAA





TT



TGTGCGCTTGT

GCGCACAGCTGCTGAGAATGAATTTGTAGCC











CTGAAAAAGG





KRT76
NM_015848
1401
ATCTCCAGACTGCTGGTTCC
1402
TCAGGGAATTAGGGGACAGA
1403
TCTGGGCTTCAGATC
1404
ATCTCCAGACTGCTGGTTCCCAGGGAACCCT









CTGACTCCC

CCCTACATCTGGGCTTCAGATCCTGACTCCC











TTCTGTCCCCTA





KRT8
NM_002273
1405
GGATGAAGCTTACATGAACAAGGT
1406
CATATAGCTGCCTGAGGAAGTTGA
1407
CGTCGGTCAGCCCTT
1408
GGATGAAGCTTACATGAACAAGGTAGAGCTG





AG

T

CCAGGC

GAGTCTCGCCTGGAAGGGCTGACCGACGAGA











TCAACTTCCT





L1CAM
NM_000425
1409
CTTGCTGGCCAAT
1410
TGATTGTCCGCAGTC
1411
ATCTACGTTGTCCAG
1412
CTTGCTGGCCAATGCCTACATCTACGTTGTC









CTGCC

CAGCTG





LAG3
NM_002286
1413
GCCTTAGAGCAAG
1414
CGGTTCTTGCTCCAGC
1415
TCTATCTTGCTCTGA
1416
GCCTTAGAGCAAGGGATTCACCCTCCGCAGG









GCCTG

CTCAG





LAMA3
NM_000227
1417
CCTGTCACTGAAG
1418
TGGGTTACTGGTCAG
1419
ATTCAGACTGACAGG
1420
CCTGTCACTGAAGCCTTGGAAGTCCAGGGGC









CCCCT

CTGTC





LAMA4
NM_002290
1421
GATGCACTGCGGT
1422
CAGAGGATACGCTCA
1423
CTCTCCATCGAGGAA
1424
GATGCACTGCGGTTAGCAGCGCTCTCCATCG









GGCAA

AGGAA





LAMA5
NM_005560
1425
CTCCTGGCCAACA
1426
ACACAAGGCCCAGCC
1427
CTGTTCCTGGAGCAT
1428
CTCCTGGCCAACAGCACTGCACTAGAAGAGG









GGCCT

CCATG





LAMB1
NM_002291
1429
CAAGGAGACTGGG
1430
CGGCAGAACTGACAG
1431
CAAGTGCCTGTACCA
1432
CAAGGAGACTGGGAGGTGTCTCAAGTGCCTG









CACGG

TACCA





LAMB3
NM_000228
1433
ACTGACCAAGCCT
1434
GTCACACTTGCAGCA
1435
CCACTCGCCATACTG
1436
ACTGACCAAGCCTGAGACCTACTGCACCCAG









GGTGC

TATGG





LAMC1
NM_002293
1437
GCCGTGATCTCAG
1438
ACCTGCTTGCCCAAG
1439
CCTCGGTACTTCATT
1440
GCCGTGATCTCAGACAGCTACTTTCCTCGGT









GCTCC

ACTTCA





LAMC2
NM_005562
1441
ACTCAAGCGGAAATTGAAGCA
1442
ACTCCCTGAAGCCGAGACACT
1443
AGGTCTTATCAGCAC
1444
ACTCAAGCGGAAATTGAAGCAGATAGGTCTT









AGTCTCCGCCTCC

ATCAGCACAGTCTCCGCCTCCTGGATTCAGT











GTCTCGGCTTC





LAPTM5
NM_006762
1445
TGCTGGACTTCTG
1446
TGAGATAGGTGGGCA
1447
TCCTGACCCTCTGCA
1448
TGCTGGACTTCTGCCTGAGCATCCTGACCCT









GCTCC

CTGCAG





LGALS3
NM_002306
1449
AGCGGAAAATGGC
1450
CTTGAGGGTTTGGGT
1451
ACCCAGATAACGCAT
1452
AGCGGAAAATGGCAGACAATTTTTCGCTCCA









CATGG

TGATG





LIG3
NM_002311
1453
GGAGGTGGAGAAG
1454
ACAGGTGTCATCAGC
1455
CTGGACGCTCAGAGC
1456
GGAGGTGGAGAAGGAGCCGGGCCAGAGACGA









TCGTC

GCTCT





LIMS1
NM_004987
1457
TGAACAGTAATGG
1458
TTCTGGGAACTGCTG
1459
ACTGAGCGCACACGA
1460
TGAACAGTAATGGGGAGCTGTACCATGAGCA









AACA

GTGTT





LOX
NM_002317
1461
CCAATGGGAGAAC
1462
CGCTGAGGCTGGTAC
1463
CAGGCTCAGCAAGCT
1464
CCAATGGGAGAACAACGGGCAGGTGTTCAGC









GAACA

TTGCT





LRP1
NM_002332
1465
TTTGGCCCAATGGGCTAAG
1466
GTCTCGATGCGGTCGTAGAAG
1467
TCCCGGCTGGGCGCC
1468
TTTGGCCCAATGGGCTAAGCCTGGACATCCC









TCTACT

GGCTGGGCGCCTCTACTGGGTGGATGCCTTC











TACGACCGCAT





LTBP2
NM_000428
1469
GCACACCCATCCT
1470
GATGGCTGGCCACGT
1471
CTTTGCAGCCCTCAG
1472
GCACACCCATCCTTGAGTCTCCTTTGCAGCC









AACTC

CTCAGA





LUM
NM_002345
1473
GGCTCTTTTGAAGGATTGGTAA
1474
AAAAGCAGCTGAAACAGCATC
1475
CCTGACCTTCATCCA
1476
GGCTCTTTTGAAGGATTGGTAAACCTGACCT









TCTCCAGCA

TCATCCATCTCCAGCACAATCGGCTGAAAGA











GGATGCTGTTT





MAGEA4
NM_002362
1477
GCATCTAACAGCC
1478
CAGAGTGAAGAATGG
1479
CAGCTTCCCTTGCCT
1480
GCATCTAACAGCCCTGTGCAGCAGCTTCCCT









CGTGT

TGCCTC





MANF
NM_006010
1481
CAGATGTGAAGCC
1482
AAGGGAATCCCCTCA
1483
TTCCTGATGATGCTG
1484
CAGATGTGAAGCCTGGAGCTTTCCTGATGAT









GCCCT

GCTGG





MAOA
NM_000240
1485
GTGTCAGCCAAAG
1486
CGACTACGTCGAACA
1487
CCGCGATACTCGCCT
1488
GTGTCAGCCAAAGCATGGAGAATCAAGAGAA









TCTCT

GGCGA





MAP3K5
NM_005923
1489
AGGACCAAGAGGC
1490
CCTGTGGCCATTTCA
1491
CAGCCCAGAGACCAG
1492
AGGACCAAGAGGCTACGGAAAAGCAGCAGAC









ATGTC

ATCTG





MAP3K7
NM_145333
1493
CAGGCAAGAACTAGTTGCAGAA
1494
CCTGTACCAGGCGAGATGTAT
1495
TGCTGGTCCTTTTCA
1496
CAGGCAAGAACTAGTTGCAGAACTGGACCAG









TCCTGGTCC

GATGAAAAGGACCAGCAAAATACATCTCGCC











TGGTACAGG





MAP4K4
NM_004834
1497
TCGCCGAGATTTC
1498
CTGTTGTCTCCGAAG
1499
AACGTTCCTTGTTCT
1500
TCGCCGAGATTTCCTGAGACTGCAGCAGGAG









CCTGC

AACAA





MAP7
NM_003980
1501
GAGGAACAGAGGT
1502
CTGCCAACTGGCTTTC
1503
CATGTACAACAAACG
1504
GAGGAACAGAGGTGTCTGCACTTCCATGTAC









CTCCG

AACAA





MAPKAPK3
NM_004635
1505
AAGCTGCAGAGATAATGCGG
1506
GTGGGCAATGTTATGGCTG
1507
ATTGGCACTGCCATC
1508
AAGCTGCAGAGATAATGCGGGATATTGGCAC









CAGTTTCTG

TGCCATCCAGTTTCTGCACAGCCATAACATT











GCCCAC





MCM2
NM_004526
1509
GACTTTTGCCCGCTACCTTTC
1510
GCCACTAACTGCTTCAGTATGAAG
1511
ACAGCTCATTGTTGT
1512
GACTTTTGCCCGCTACCTTTCATTCCGGCGT







AG

CACGCCGGA

GACAACAATGAGCTGTTGCTCTTCATACTGA











AGCAGTTAGTGG





MCM3
NM_002388
1513
GGAGAACAATCCC
1514
ATCTCCTGGATGGTG
1515
TGGCCTTTCTGTCTA
1516
GGAGAACAATCCCCTTGAGACAGAATATGGC









CAAGG

CTTTC





MCM6
NM_005915
1517
TGATGGTCCTATGTGTCACATTCA
1518
TGGGACAGGAAACACACCAA
1519
CAGGTTTCATACCAA
1520
TGATGGTCCTATGTGTCACATTCATCACAGG









CACAGGCTTCAGCAC

TTTCATACCAACACAGGCTTCAGCACTTCCT











TTGGTGTGTTTC





MDK
NM_002391
1521
GGAGCCGACTGCA
1522
GACTTTGGTGCCTGT
1523
ATCACACGCACCCCA
1524
GGAGCCGACTGCAAGTACAAGTTTGAGAACT









GTTCT

GGGGT





MDM2
NM_002392
1525
CTACAGGGACGCC
1526
ATCCAACCAATCACC
1527
CTTACACCAGCATCA
1528
CTACAGGGACGCCATCGAATCCGGATCTTGA









AGATC

TGCTG





MELK
NM_014791
1529
AGGATCGCCTGTC
1530
TGCACATAAGCAACA
1531
CCCGGGTTGTCTTCC
1532
AGGATCGCCTTGTCAGAAGAGGAGACCCGGG









GTCAG

GTTGTCT





MET
NM_000245
1533
GACATTTCCAGTCCTGCAGTCA
1534
CTCCGATCGCACATTTGT
1535
TGCCTCTCTGCCCCA
1536
GACATTTCCAGTCCTGCAGTCAATGCCTCTC









CCCTTTGT

TGCCCCACCCTTTGTTCAGTGTGGCTGGTGC











CACGACAAATGT





MGMT
NM_002412
1537
GTGAAATGAAACG
1538
GACCCTGCTCACAAC
1539
CAGCCCTTTGGGGAA
1540
GTGAAATGAAACGCACCACACTGGACAGCCC









GCTGG

TTTGT





MGST1
NM_020300
1541
ACGGATCTACCACACCATTGC
1542
TCCATATCCAACAAAAAAACTCAA
1543
TTTGACACCCCTTCC
1544
ACGGATCTACCACACCATTGCATATTTGACA







AG

CCAGCCA

CCCCTTCCCCAGCCAAATAGAGCTTTGAGTT











TTTTTGTTGGAT





MICA
NM_000247
1545
ATGGTGAATGTCA
1546
AAGCCAGAAGCCCTG
1547
CGAGGCCTCAGAGGG
1548
ATGGTGAATGTCACCCGCAGCGAGGCCTCAG









CAAC

AGGGC





MKI67
NM_002417
1549
GATTGCACCAGGG
1550
TCCAAAGTGCCTCTG
1551
CCACTCTTCCTTGAA
1552
GATTGCACCAGGGCAGAACAGGGGAGGGTGT









CACCC

TCAAG





MLXIP
NM_014938
1553
TGCTTAGCTGGCA
1554
CAGCCTACTCTCCAT
1555
CATGAGATGCCAGGA
1556
TGCTTAGCTGGCATGTGGCCGCATGAGATGC









GACCC

CAGGA





MMP11
NM_005940
1557
CCTGGAGGCTGCAACATACC
1558
TACAATGGCTTTGGAGGATAGCA
1559
ATCCTCCTGAAGCCC
1560
CCTGGAGGCTGCAACATACCTCAATCCTGTC









TTTTCGCAGC

CCAGGCCGGATCCTCCTGAAGCCCTTTTCGC











AGCACTGCTAT





MMP2
NM_004530
1561
CAGCCAGAAGCGG
1562
AGACACCATCACCTG
1563
AAGTCCGAATCTCTG
1564
CAGCCAGAAGCGGAAACTTAAAAAGTCCGAA









CTCCC

TCTCT





MMP7
NM_002423
1565
GGATGGTAGCAGTCTAGGGATTAA
1566
GGAATGTCCCATACCCAAAGAA
1567
CCTGTATGCTGCAAC
1568
GGATGGTAGCAGTCTAGGGATTAACTTCCTG





CT



TCATGAACTTGGC

TATGCTGCAACTCATGAACTTGGCCATTCTT











TGGGTATGGGAC





MMP9
NM_004994
1569
GAGAACCAATCTC
1570
CACCCGAGTGTAACC
1571
ACAGGTATTCCTCTG
1572
GAGAACCAATCTCACCGACAGGCAGCTGGCA









CCAGC

GAGGA





MPPED2
NM_001584
1573
CCGACCAACCCTC
1574
AGGGCATTTAGAGCT
1575
ATTTGACCTTCCAAA
1576
CCGACCAACCCTCCAATTATATTTGACCTTC









CCCAC

CAAACC





MRC1
NM_002438
1577
CTTGACCTCAGGA
1578
GGACTGCGGTCACTC
1579
CCAACCGCTGTTGAA
1580
CTTGACCTCAGGACTCTGGATTGGACTTAAC









GCTCA

AGTCTG





MRPL13
NM_014078
1581
TCCGGTTCCCTTCG
1582
GTGGAAAAACTGCGG
1583
CGGCTGGAAATTATG
1584
TCCGGTTCCCTTCGTTTAGGTCGGCTGGAAA









TCCTC

TATGT





MSH2
NM_000251
1585
GATGCAGAATTGA
1586
TCTTGGCAAGTCGGT
1587
CAAGAAGATTTACTT
1588
GATGCAGAATTGAGGCAGACTTTACAAGAAG









CGTCG

ATTTA





MSH3
NM_002439
1589
TGATTACCATCATGGCTCAGA
1590
CTTGTGAAAATGCCATCCAC
1591
TCCCAATTGTCGCTT
1592
TGATTACCATCATGGCTCAGATTGGCTCCTA









CTTCTGCAG

TGTTCCTGCAGAAGAAGCGACAATTGGGATT











GTGGATGGCAT





MSH6
NM_000179
1593
TCTATTGGGGGAT
1594
CAAATTGCGAGTGGT
1595
CCGTTACCAGCTGGA
1596
TCTATTGGGGGATTGGTAGGAACCGTTACCA









AATTC

GCTGG





MTA1
NM_004689
1597
CCGCCCTCACCTGAAGAGA
1598
GGAATAAGTTAGCCGCGCTTCT
1599
CCCAGTGTCCGCCAA
1600
CCGCCCTCACCTGCAGAGAAACGCGCTCCTT









GGAGCG

GGCGGACACTGGGGGAGGAGAGGAAGAAGCG











CGGCTAACTT





MTPN
NM_145808
1601
GGTGGAAGGAAAC
1602
CAGCAGCAGAAATTC
1603
AAGCTGCCCACAATC
1604
GGTGGAAGGAAACCTCTTCATTATGCAGCAG









TGCTG

ATTGT





MTSS1
NM_014751
1605
TTCGACAAGTCCT
1606
CTTGGAACATCCGTC
1607
CCAAGAAACAGCGAC
1608
TTCGACAAGTCCTCCACCATTCCAAGAAACA









ATCA

GCGAC





MUC1
NM_002456
1609
GGCCAGGATCTGTGGTGGTA
1610
CTCCACGTCGTGGACATTGA
1611
CTCTGGCCTTCCGAG
1612
GGCCAGGATCTGTGGTGGTACAATTGACTCT









AAGGTACC

GGCCTTCCGAGAAGGTACCATCAATGTCCAC











GACGTGGAG





MVP
NM_017458
1613
ACGAGAACGAGGGCATCTATGT
1614
GCATGTAGGTGCTTCCAATCAC
1615
CGCACCTTTCCGGTC
1616
ACGAGAACGAGGGCATCTATGTGCAGGATGT









TTGACATCCT

CAAGACCGGAAAGGTGCGCGCTGTGATTGGA











AGCACCTACA





MYBL2
NM_002466
1617
GCCGAGATCGCCAAGATG
1618
CTTTTGATGGTAGAGTTCCAGTGA
1619
CAGCATTGTCTGTCC
1620
GCCGAGATCGCCAAGATGTTGCCAGGGAGGA







TTC

TCCCTGGCA

CAGACAATGCTGTGAAGAATCACTGGAACTC











TACCATCAAA





MYBPC1
NM_002465
1621
CAGCAACCAGGGA
1622
CAGCAGTAAGTGCCT
1623
AAATTCGCAAGCCCA
1624
CAGCAACCAGGGAGTCTGTACCCTGGAAATT









GCCCC

CGCAA





MYC
NM_002467
1625
TCCCTCCACTCGGAAGGACTA
1626
CGGTTGTTGCTGATCTGTCTCA
1627
TCTGACACTGTCCAA
1628
TCCCTCCACTCGGAAGGACTATCCTGCTGCC









CTTGACCCTCTT

AAGAGGGTCAAGTTGGACAGTGTCAGAGTCC











TGAGACAGAT





MYLK3
NM_182493
1629
CACCTGACTGAGCTGGATGT
1630
GATGTAGTGCTGGTGCAGGT
1631
CACACCCTCACAGAT
1632
CACCTGACTGAGCTGGATGTGGTCCTGTTCA









CTGCCTGGT

CCAGGCAGATCTGTGAGGGTGTGCATTACCT











GCACCAGCACT





MYO6
NM_004999
1633
AAGCAGTTCTGGA
1634
GATGAGCTCGGCTTC
1635
CAATCCTCAGGGCCA
1636
AAGCAGTTCTGGAGCAGGAGCGCAGGGACCG









GCTCC

GGAGC





NCAM1
NM_000615
1637
TAGTTCCCAGCTG
1638
CAGCCTTGTTCTCAGC
1639
CTCAGCCTCGTCGTT
1640
TAGTTCCCAGCTGACCATCAAAAAGGTGGAT









CTTAT

AAGAA





NCAPD3
NM_015261
1641
TCGTTGCTTAGAC
1642
CTCCAGACAGTGTGC
1643
CTACTGTCCGCAGCA
1644
TCGTTGCTTAGACAAGGCGCCTACTGTCCGC









AGGCA

AGCAA





NCOR1
NM_006311
1645
AACCGTTACAGCC
1646
TCTGGAGAGACCCTT
1647
CCAGGCTCAGTCTGT











CCATC
1648
AACCGTTACAGCCCAGAATCCCAGGCTCAGT











CTGTCC





NCOR2
NM_006312
1649
CGTCATCTACGAA
1650
GAGCACTGGGTCACA
1651
CCTCATAGGACAAGA
1652
CGTCATCTACGAAGGCAAGAAGGGCCACGTC









CGTGG

TTGTC





NDRG1
NM_006096
1653
AGGGCAACATTCC
1654
CAGTGCTCCTACTCC
1655
CTGCAAGGACACTCA
1656
AGGGCAACATTCCACAGCTGCCCTGGCTGTG









TCACA

ATGAG





NDUFS5
NM_004552
1657
AGAAGAGTCAAGG
1658
AGGCCGAACCTTTTC
1659
TGTCCAAGAAAGGCA
1660
AGAAGAGTCAAGGGCACGAGCATCGGGTAGC









TGGCT

CATGC





NEK2
NM_002497
1661
GTGAGGCAGCGCGACTCT
1662
TGCCAATGGTGTACAACACTTCA
1663
TGCCTTCCCGGGCTG
1664
GTGAGGCAGCGCGACTCTGGCGACTGGCCGG









AGGACT

CCATGCCTTCCCGGGCTGAGGACTATGAAGT











GTTGTACACC





NETO2
NM_018092
1665
CCAGGGCACCATA
1666
AACGGTAAATCAAGG
1667
AGCCAACCCTTTTCT
1668
CCAGGGCACCATACTGTTTCCAGCAGCCAAC









CCCAT

CCTTTT





NEXN
NM_144573
1669
AGGAGGAGGAAGA
1670
GAGCTCCTGATCTGG
1671
TCATCTTCAGCAGTG
1672
AGGAGGAGGAAGAAGGTAGCATCATGAATGG









GAGCC

CTCCA





NFAT5
NM_006599
1673
CTGAACCCCTCTC
1674
AGGAAACGATGGCGA
1675
CGAGAATCAGTCCCC
1676
CTGAACCCCTCTCCTGGTCACCGAGAATCAG









GTGGA

TCCCCG





NFATC2
NM_173091
1677
CAGTCAAGGTCAG
1678
CTTTGGCTCGTGGCAT
1679
CGGGTTCCTACCCCA
1680
CAGTCAAGGTCAGAGGCTGAGCCCGGGTTCC









CAGTC

TACCC





NFKB1
NM_003998
1681
CAGACCAAGGGAGA
1682
AGCTGCCAGTGCTAT
1683
AAGCTGTAAACATGA
1684
CAGACCAAGGAGATGGACCTCAGCGTGGTGC









GCCGC

GGCTC





NFKBIA
NM_020529
1685
CTACTGGACGACC
1686
CCTTGACCATCTGCTC
1687
CTCGTCTTTCATGGA
1688
CTACTGGACGACCGCCACGACAGCGGCCTGG









GTCCA

ACTCC





NME1
NM_000269
1689
CCAACCCTGCAGACTCCAA
1690
ATGTATAATGTTCCTGCCAACTTG
1691
CCTGGGACCATCCGT
1692
CCAACCCTGCAGACTCCAAGCCTGGGACCAT







TATG

GGAGACTTCT

CCGTGGAGACTTCTGCATACAAGTTGGCAGG











AACATTATAC





NNMT
NM_006169
1694
CCTAGGGCAGGGA
1694
CTAGTCCAGCCAAAC
1695
CCCTCTCCTCATGCC
1696
CCTAGGGCAGGGATGGAGAGAGAGTCTGGGC









CAGAC

ATGAG





NOS3
NM_000603
1697
ATCTCCGCCTCGC
1698
TCGGAGCCATACAGG
1699
TTCACTCGCTTCGCC
1700
ATCTCCGCCTCGCTCATGGGCACGGTGATGG









ATCAC

CGAAG





NOX4
NM_016931
1701
CCTCAACTGCAGCCTTATCC
1702
TGCTTGGAACCTTCTGTGAT
1703
CCGAACACTCTTGGC
1704
CCTCAACTGCAGCCTTATCCTTTTACCCATG









TTACCTCCG

TGCCGAACACTCTTGGCTTACCTCCGAGGAT











CACAGAAGGTTC





NPBWR1
NM_005285
1705
TCACCAACCTGTT
1706
GATGTTGATGGGCAG
1707
ATCGCCGACGAGCTC
1708
TCACCAACCTGTTCATCCTCAACCTGGCCAT









TTCAC

CGCCGA





NPM1
NM_002520
1709
AATGTTGTCCAGGTTCTATTGC
1710
CAAGCAAAGGGTGGAGTTC
1711
AACAGGCATTTTGGA
1712
AATGTTGTCCAGGTTCTATTGCCAAGAATGT









CAACACATTCTTG

GTTGTCCAAAATGCCTGTTTAGTTTTTAAAG











ATGGAACTCCAC





NRG1
NM_013957
1713
CGAGACTCTCCTCATAGTGAAAGG
1714
CTTGGCGTGTGGAAATCTACAG
1715
ATGACCACCCCGGCT
1716
CGAGACTCTCCTCATAGTGAAAGGTATGTGT





TA



CGTATGTCA

CAGCCATGACCACCCCGGCTCGTATGTCACC











TGTAGATTTCC





NRIP3
NM_020645
1717
CCCACAAGCATGA
1718
TGCTCAATCTGGCCC
1719
AGCTTTCTCTACCCC
1720
CCCACAAGCATGAAGGAGAAAAGCTTTCTCT









GGCAT

ACCCC





NRP1
NM_003873
1721
CAGCTCTCTCCACGCGATTC
1722
CCCAGCAGCTCCATTCTGA
1723
CAGGATCTACCCCGA
1724
CAGCTCTCTCCACGCGATTCATCAGGATCTA









GAGAGCCACTCAT

CCCCGAGAGAGCCACTCATGGCGGACTGGGG











CTCAGAATGGA





NUP62
NM_153719
1725
AGCCTCTTTGCGTCAATAGC
1726
CTGTGGTCACAGGGGTACAG
1727
TCATCTGCCACCACT
1728
AGCCTCTTTGCGTCAATAGCAACTGCTCCAA









GGACTCTCC

CCTCATCTGCCACCACTGGACTCTCCCTCTG











TACCCCTGTGAC





OAZ1
NM_004152
1729
AGCAAGGACAGCT
1730
GAAGACATGGTCGGC
1731
CTGCTCCTCAGCGAA
1732
AGCAAGGACAGCTTTGCAGTTCTCCTGGAGT









CTCCA

TCGCTG





OCLN
NM_002538
1733
CCCTCCCATCCGA
1734
GACGCGGGAGTGTAG
1735
CTCCTCCCTCGGTGA
1736
CCCTCCCATCCGAGTTTCAGGTGAATTGGTC









CCAAT

ACCGAG





ODC1
NM_002539
1737
AGAGATCACCGGCGTAATCAA
1738
CGGGCTCAGCTATGATTCTCA
1739
CCAGCGTTGGACAAA
1740
AGAGATCACCGGCGTAATCAACCCAGCGTTG









TACTTTCCGTCA

GACAAATACTTTCCGTCAGACTCTGGAGTGA











GAATCATAGCT





OLFML2
NM_015441
1741
CATGTTGGAAGGA
1742
CACCAGTTTGGTGGT
1743
TGGCCTGGATCTCCT
1744
CATGTTGGAAGGAGCGTTCTATGGCCTGGAT









GAAGC

CTCCTG





OLFML3
NM_020190
1745
TCAGAACTGAGGC
1746
CCAGATAGTCTACCT
1747
CAGACGATCCACTCT
1748
TCAGAACTGAGGCCGACACCATCTCCGGGAG









CCCGG

AGTGG





OMD
NM_005014
1749
CGCAAACTCAAGACTATCCCA
1750
CAGTCACAGCCTCAATTTCATT
1751
TCCGATGCACATTCA
1752
CGCAAACTCAAGACTATCCCAAATATTCCGA









GCAACTCTACC

TGCACATTCAGCAACTCTACCTTCAGTTCAA











TGAAATTGAGG





OR51E1
NM_152430
1753
GCATGCTTTCAGG
1754
AGAAGATGGCCAGCA
1755
TCCTCATCTCCACCT
1756
GCATGCTTTCAGGCATTGACATCCTCATCTC









CATCC

CACCTC





OR51E2
NM_030774
1757
TATGGTGCCAAAA
1758
GTCCTTGTCACAGCT
1759
ACATAGCCAGCACCC
1760
TATGGTGCCAAAACCAAACAGATCAGAACAC









GTGTT

GGGTG





OSM
NM_020530
1761
GTTTCTGAAGGGG
1762
AGGTGTCTGGTTTGG
1763
CTGAGCTGGCCTCCT
1764
GTTTCTGAAGGGGAGGTCACAGCCTGAGCTG









ATGCC

GCCTC





PAGE1
NM_003785
1765
CAACCTGACGAAGTGGAATC
1766
CAGATGCTCCCTCATCCTCT
1767
CCAACTCAAAGTCAG
1768
CAACCTGACGAAGTGGAATCACCAACTCAAA









GATTCTACACCTGC

GTCAGGATTCTACACCTGCTGAAGAGAGAGA











GGATGAGGGA





PAGE4
NM_007003
1769
GAATCTCAGCAAGAGGAACCA
1770
GTTCTTCGATCGGAGGTGTT
1771
CCAACTGACAATCAG
1772
GAATCTCAGCAAGAGGAACCACCAACTGACA









GATATTGAACCTGG

ATCAGGATATTGAACCTGGACAAGAGAGAGA











AGGAACACCT





PAK6
NM_020168
1773
CCTCCAGGTCACC
1774
GTCCCTTCAGGCCAG
1775
AGTTTCAGGAAGGCT
1776
CCTCCAGGTCACCCACAGCCAGTTTCAGGAA









GCCCC

GGCTG





PATE1
NM_138294
1777
TGGTAATCCCTGG
1778
TCCACCTTATGCCTTT
1779
CAGCACAGTTCTTTA
1780
TGGTAATCCCTGGTTAACCTTCATGGGCTGC









GGCAG

CTAAAG





PCA3
NM_015342
1781
CGTGATTGTCAGG
1782
AGAAAGGGGAGATGC
1783
CTGAGATGCTCCCTG
1784
CGTGATTGTCAGGAGCAAGACCTGAGATGCT









CCTTC

CCCTG





PCDHGB
NM_018927
1785
CCCAGCGTTGAAG
1786
GAAACGCCAGTCCGT
1787
ATTCTTAAACAGCAA
1788
CCCAGCGTTGAAGCAGATAAGAAGATTCTTA









GCCCC

AACAG





PCNA
NM_002592
1789
GAAGGTGTTGGAG
1790
GGTTTACACCGCTGG
1791
ATCCCAGCAGGCCTC
1792
GAAGGTGTTGGAGGCACTCAAGGACCTCATC









GTTGA

AACGA





PDE9A
NM_001001570
1793
TTCCACAACTTCCGGCAC
1794
AGACTGCAGAGCCAGACCA
1795
TACATCATCTGGGCC
1796
TTCCACAACTTCCGGCACTGCTTCTGCGTGG









ACGCAGAAG

CCCAGATGATGTACAGCATGGTCTGGCTCTG











CAGTCT





PDGFRB
NM_002609
1797
CCAGCTCTCCTTCC
1798
GGGTGGCTCTCACTT
1799
ATCAATGTCCCTGTC
1800
CCAGCTCTCCTTCCAGCTACAGATCAATGTC









CGAGT

CCTGTC





PECAM1
NM_000442
1801
TGTATTTCAAGACCTCTGTGCACT
1802
TTAGCCTGAGGAATTGCTGTGTT
1803
TTTATGAACCTGCCC
1804
TGTATTTCAAGACCTCTGTGCACTTATTTAT





T



TGCTCCCACA

GAACCTGCCCTGCTCCCACAGAACACAGCAA











TTCCTCAGGCT





PEX10
NM_153818
1805
GGAGAAGTTCCCTCCCCAG
1806
ATCTGTGTCCAGGCCCAC
1807
CTACCTTCGGCACTA
1808
GGAGAAGTTCCCTCCCCAGAAGCTCATCTAC









CCGCTGAGC

CTTCGGCACTACCGCTGAGCCGGCGCCCGGG











TGGGCCTGGAC





PGD
NM_002631
1809
ATTCCCATGCCCT
1810
CTGGCTGGAAGCATC
1811
ACTGCCCTCTCCTTC
1812
ATTCCCATGCCCTGTTTTACCACTGCCCTCT









TATGA

CCTTCT





PGF
NM_002632
1813
GTGGTTTTCCCTCG
1814
AGCAAGGGAACAGCC
1815
ATCTTCTCAGACGTC
1816
GTGGTTTTCCCTCGGAGCCCCCTGGCTCGGG









CCGAG

ACGTCT





PGK1
NM_000291
1817
AGAGCCAGTTGCTGTAGAACTCAA
1818
CTGGGCCTACACAGTCCTTCA
1819
TCTCTGCTGGGCAAG
1820
AGAGCCAGTTGCTGTAGAACTCAAATCTCTG









GATGTTCTGTTC

CTGGGCAAGGATGTTCTGTTCTTGAAGGACT











GTGTAGGCCCA





PGR
NM_000296
1821
GATAAAGGAGCCG
1822
TCACAAGTCCGGCAC
1823
TAAATTGCCGTCGCA
1824
GATAAAGGAGCCGCGTGTCACTAAATTGCCG









GCCGC

TCGCA





PHTF2
NM_020432
1825
GATATGGCTGATG
1826
GGTTTGGGTGTTCTTG
1827
ACAATCTGGCAATGC
1828
GATATGGCTGATGCTGCTCCTGGGAACTGTG









ACAGT

CATTGC





PIK3C2A
NM_002645
1829
ATACCAATCACCGCACAAACC
1830
CACACTAGCATTTTCTCCGCATA
1831
TGTGCTGTGACTGGA
1832
ATACCAATCACCGCACAAACCCAGGCTATTT









CTTAACAAATAGCCT

GTTAAGTCCAGTCACAGCACAAAGAAACATA











TGCGGAGAAAA





PIK3CA
NM_006218
1833
GTGATTGAAGAGC
1834
GTCCTGCGTGGGAAT
1835
TCCTGCTTCTCGGGA
1836
GTGATTGAAGAGCATGCCAATTGTTCTGTAT









TACAG

CCCGA





PIK3CG
NM_002649
1837
GGAGAACTCAATG
1838
TGATGCTTAGGCAGG
1839
TTCTGGACAATTACT
1840
GGAGAACTCAATGTCCATCTCCATTCTTCTG









GCCAC

GACAAT





PIM1
NM_002648
1841
CTGCTCAAGGACA
1842
GGATCCACTCTGGAG
1843
TACACTCGGGTCCCA
1844
CTGCTCAAGGACACCGTCTACACGGACTTCG









TCGAA

ATGGG





PLA2G7
NM_005084
1845
CCTGGCTGTGGTT
1846
TGACCCATGCTGATG
1847
TGGCAATACATAAAT
1848
CCTGGCTGTGGTTTATCCTTTTGACTGGCAA









CCTGT

TACATA





PLAU
NM_002658
1849
GTGGATGTGCCCT
1850
CTGCGGATCCAGGGT
1851
AAGCCAGGCGTCTAC
1852
GTGGATGTGCCCTGAAGGACAAGCCAGGCGT









ACGAG

CTACA





PLAUR
NM_002659
1853
CCCATGGATGCTC
1854
CCGGTGGCTACCAGA
1855
CATTGACTGCCGAGG
1856
CCCATGGATGCTCCTCTGAAGAGACTTTCCT









CCCCA

CATTGA





PLG
NM_000301
1857
GGCAAAATTTCCA
1858
ATGTATCCATGAGCG
1859
TGCCAGGCCTGGGAC
1860
GGCAAAATTTCCAAGACCATGTCTGGACTGG









TCTCA

AATGC





PLK1
NM_005030
1861
AATGAATACAGTATTCCCAAGCAC
1862
TGTCTGAAGCATCTTCTGGATGA
1863
AACCCCGTGGCCCGC
1864
AATGAATACAGTATTCCCAAGCACATCAACC





AT



CTCC

CCGTGGCCGCCTCCCTCATCCAGAAGATGCT











TCAGACA





PLOD2
NM_000935
1865
CAGGGAGGTGGTTGCAAAT
1866
TCTCCCAGGATGCATGAAG
1867
TCCAGCCTTTTCGTG
1868
CAGGGAGGTGGTTGCAAATTTCTAAGGTACA









GTGACTCAA

ATTGCTCTATTGAGTCACCACGAAAAGGCTG











GAGCTTCATG





PLP2
NM_002668
1869
CCTGATCTGCTTCA
1870
GCAGCAAGGATCATC
1871
ACACCAGGCTACTCC
1872
CCTGATCTGCTTCAGTGCCTCCACACCAGGC









TCCCT

TACTCC





PNLIPRP
NM_005396
1873
TGGAGAAGGTGAA
1874
CACGGCTTGGGTGTA
1875
ACCCGTGCCTCCAGT
1876
TGGAGAAGGTGAACTGCATCTGTGTGGACTG









CCACA

GAGGC





POSTN
NM_006475
1877
GTGGCCCAATTAG
1878
TCACAGGTGCCAGCA
1879
TTCTCCATCTGGCCT
1880
GTGGCCCAATTAGGCTTGGCATCTGCTCTGA









CAGAG

GGCCA





PPAP2B
NM_003713
1881
ACAAGCACCATCC
1882
CACGAAGAAAACTA
1883
ACCAGGGCTCCTTGA
1884
ACAAGCACCATCCCAGTGATGTTCTGGCAGG









GCAAA

ATTTGC





PPFIA3
NM_003660
1885
CCTGGAGCTCCGT
1886
AGCCACATAGGGATC
1887
CACCCACTTTACCTT
1888
CCTGGAGCTCCGTTACTCTCAGGCACCCACT









CTGGT

TTACCT





PPP1R12A
NM_002480
1889
CGGCAAGGGGTTGATATAGA
1890
TGCCTGGCATCTCTAAGCA
1891
CCGTTCTTCTTCCTT
1892
CGGCAAGGGGTTGATATAGAAGCAGCTCGAA









TCGAGCTGC

AGGAAGAAGAACGGATCATGCTTAGAGATGC











CAGGCA





PPP3CA
NM_000944
1893
ATACTCCGAGCCC
1894
GGAAGCCTGTTGTTT
1895
TACATGCGGTACCCT
1896
ATACTCCGAGCCCACGAAGCCCAAGATGCAG









GCATC

GGTAC





PRIMA1
NM_178013
1897
ATCCTCTTCCCTGA
1898
CCCAGCTGAGAGGGA
1899
TGACGCATCCAGGGC
1900
ATCCTCTTCCCTGAGCCGCTGACGCATCCAG









TCTAG

GGCTCT





PRKAR1
NM_002735
1901
ACAAAACCATGAC
1902
TGTCATCCAGGTGAG
1903
AAGGCCATCTCCAAG
1904
ACAAAACCATGACTGCGCTGGCCAAGGCCAT









AACGT

CTCCA





PRKAR2B
NM_002736
1905
TGATAATCGTGGGAGTTTCG
1906
GCACCAGGAGAGGTAGCAGT
1907
CGAACTGGCCTTAAT
1908
TGATAATCGTGGGAGTTTCGGCGAACTGGCC









GTACAATACACCCA

TTAATGTACAATACACCCAGAGCAGCTACAA











TCACTGCTAC





PRKCA
NM_002737
1909
CAAGCAATGCGT
1910
GTAAATCCGCCCCCT
1911
CAGCCTCTGCGGAAT
1912
CAAGCAATGCGTCATCAATGTCCCCAGCCTC









GGATC

TGCGG





PRKCB
NM_002738
1913
GACCCAGCTCCAC
1914
CCCATTCACGTACTCC
1915
CCAGACCATGGACCG
1916
GACCCAGCTCCACTCCTGCTTCCAGACCATG









CCTGT

GACCGC





PROM1
NM_006017
1917
CTATGACAGGCAT
1918
CTCCAACCATGAGGA
1919
ACCCGAGGCTGTGTC
1920
CTATGACAGGCATGCCACCCCGACCACCCGA









TCCAA

GGCTG





PROS1
NM_000313
1921
GCAGCACAGGAAT
1922
CCCACCTATCCAACCT
1923
CTCATCCTGACAGAC
1924
GCAGCACAGGAATCTTCTTCTTGGCAGCTGC









TGCAG

AGTCTG





PSCA
NM_005672
1925
ACCGTCATCAGCAAAGGCT
1926
CGTGATGTTCTTCTTGCCC
1927
CCTGTGAGTCATCCA
1928
ACCGTCATCAGCAAAGGCTGCAGCTTGAACT









CGCAGTTCA

GCGTGGATGACTCACAGGACTACTACGTGGG











CAAGAAGAAC





PSMD13
NM_002817
1929
GGAGGAGCTCTACACGAAGAAG
1930
CGGATCCTGCACAAAATCA
1931
CCTGAAGTGTCAGCT
1932
GGAGGAGCTCTACACGAAGAAGTTGTGGCAT









GATGCCACA

CAGCTGACACTTCAGGTGCTTGATTTTGTGC











AGGATCCG





PTCH1
NM_000264
1933
CCACGACAAAGCC
1934
TACTCGATGGGCTCT
1935
CCTGAAACAAGGCTG
1936
CCACGACAAAGCCGACTACATGCCTGAAACA









AGAAT

AGGCT





PTEN
NM_000314
1937
TGGCTAAGTGAAGATGACAATCAT
1938
TGCACATATCATTACACCAGTTCG
1939
CCTTTCCAGCTTTAC
1940
TGGCTAAGTGAAGATGACAATCATGTTGCAG





G

T

AGTGAATTGCTGCA

CAATTCACTGTAAAGCTGGAAAGGGACGAAC











TGGTGTAATG





PTGER3
NM_000957
1941
TAACTGGGGCAAC
1942
TTGCAGGAAAAGGTG
1943
CCTTTGCCTTCCTGG
1944
TAACTGGGGCAACCTTTTCTTCGCCTCTGCC









GGCTC

TTTGCC





PTGS2
NM_000963
1945
GAATCATTCACCAGGCAAATTG
1946
CTGTACTGCGGGTGGAACAT
1947
CCTACCACCAGCAAC
1948
GAATCATTCACCAGGCAAATTGCTGGCAGGG









CCTGCCA

TTGCTGGTGGTAGGAATGTTCCACCCGCAGT











ACAG





PTH1R
NM_000316
1949
CGAGGTACAAGCTGAGATCAAGAA
1950
GCGTGCCTTTCGCTTGAA
1951
CCAGTGCCAGTGTCC
1952
CGAGGTACAAGCTGAGATCAAGAAATCTTGG









AGCGGCT

AGCCGCTGGACACTGGCACTGGACTTCAAGC











GAAAGGCACG





PTHLH
NM_002820
1953
AGTGACTGGGAGTGGGCTAGAA
1954
AAGCCTGTTACCGTGAATCGA
1955
TGACACCTCCACAAC
1956
AGTGACTGGGAGTGGGCTAGAAGGGGACCAC









GTCGCTGGA

CTGTCTGACACCTCCACAACGTCGCTGGAGC











TCGATTCACG





PTK2
NM_005607
1957
GACCGGTCGAATG
1958
CTGGACATCTCGATG
1959
ACCAGGCCCGTCACA
1960
GACCGGTCGAATGATAAGGTGTACGAGAATG









TTCTC

TGACG





PTK2B
NM_004103
1961
CAAGCCCAGCCGA
1962
GAACCTGGAACTGCA
1963
CTCCGCAAACCAACC
1964
CAAGCCCAGCCGACCTAAGTACAGACCCCCT









TCCTG

CCGCA





PTK6
NM_005975
1965
GTGCAGGAAAGGTTCACAAA
1966
GCACACACGATGGAGTAAGG
1967
AGTGTCTGCGTCCAA
1968
GTGCAGGAAAGGTTCACAAATGTGGAGTGTC









TACACGCGT

TGCGTCCAATACACGCGTGTGCTCCTCTCCT











TACTCCATCGT





PTK7
NM_002821
1969
TCAGAGGACTCA
1970
CATACACCTCCACGC
1971
CGCAAGGTCCCATTC
1972
TCAGAGGACTCACGGTTCGAGGTCTTCAAGA









TTGAA

ATGGG





PTPN1
NM_002827
1973
AATGAGGAAGTTT
1974
CTTCGATCACAGCCA
1975
CTGATCCAGACAGCC
1976
AATGAGGAAGTTTCGGATGGGGCTGATCCAG









GACCA

ACAGC





PTPRK
NM_002844
1977
TCAAACCCTCCCA
1978
AGCAGCCAGTTCGTC
1979
CCCCATCGTTGTACA
1980
TCAAACCCTCCCAGTGCTGGCCCCATCGTTG









TTGCA

TACATT





PTTG1
NM_004219
1981
GGCTACTCTGATCTATGTTGATAA
1982
GCTTCAGCCCATCCTTAGCA
1983
CACACGGGTGCCTGG
1984
GGCTACTCTGATCTATGTTGATAAGGAAAAT





GG



TTCTCCA

GGAGAACCAGGCACCCGTGTGGTTGCTAAGG











ATGGGCTGAA





PYCARD
NM_013258
1985
CTTTATAGACCAG
1986
AGCATCCAGCAGCCA
1987
ACGTTTGTGACCCTC
1988
CTTTATAGACCAGCACCGGGCTGCGCTTATC









GCGAT

GCGAG





RAB27A
NM_004580
1989
TGAGAGATTAATG
1990
CCGGATGCTTTATTCG
1991
ACAAATTGCTTCTCA
1992
TGAGAGATTAATGGGCATTGTGTACAAATTG









CCATC

CTTCTC





RAB30
NM_014488
1993
TAAAGGCTGAGGC
1994
CTCCCCAGCATCTCAT
1995
CCATCAGGGCAGTTG
1996
TAAAGGCTGAGGCACGGAGAAGAAAAGGAAT









CTGAT

CAGCA





RAB31
NM_006868
1997
CTGAAGGACCCTA
1998
ATGCAAAGCCAGTGT
1999
CTTCTCAAAGTGAGG
2000
CTGAAGGACCCTACGCTCGGTGGCCTGGCAC









TGCCA

CTCAC





RAD21
NM_006265
2001
TAGGGATGGTATCTGAAACAACA
2002
TCGCGTACACCTCTGCTC
2003
CACTTAAAACGAATC
2004
TAGGGATGGTATCTGAAACAACAATGGTCAC









TCAAGAGGGTGACCA

CCTCTTGAGATTCGTTTTAAGTGTAATTCCA











TAATGAGCAGAG





RAD51
NM_002875
2005
AGACTACTCGGGT
2006
AGCATCCGCAGAAAC
2007
CTTTCAGCCAGGCAG
2008
AGACTACTCGGGTCGAGGTGAGCTTTCAGCC









ATGCA

AGGCA





RAD9A
NM_004584
2009
GCCATCTTCACCA
2010
CGGTGTCTGAGAGTG
2011
CTTTGCTGGACGGCC
2012
GCCATCTTCACCATCAAGGACTCTTTGCTGG









ACTTT

ACGGCC





RAF1
NM_002880
2013
CGTCGTATGCGAG
2014
TGAAGGCGTGAGGTG
2015
TCCAGGATGCCTGTT
2016
CGTCGTATGCGAGATCTGTTTCCAGGATGCC









AGTTC

TGTTA





RAGE
NM_014226
2017
ATTAGGGGACTTT
2018
GGGTGGAGATGTATT
2019
CCGGAGTGTCTATTC
2020
ATTAGGGGACTTTGGCTCCTGCCGGAGTGTC









CAAGC

TATTCC





RALA
NM_005402
2021
TGGTCCTGAATGT
2022
CCCCATTTCACCTCTT
2023
TTGTGTTTCTTGGGC
2024
TGGTCCTGAATGTAGCGTGTAAGCTTGTGTT









AGTCT

TCTTGG





RALBP1
NM_006788
2025
GGTGTCAGATATAAATGTGCAAAT
2026
TTCGATATTGCCAGCAGCTATAAA
2027
TGCTGTCCTGTCGGT
2028
GGTGTCAGATATAAATGTGCAAATGCCTTCT





GC



CTCAGTACGTTCA

TGCTGTCCTGTCGGTCTCAGTACGTTCACTT











TATAGCTGCTGG





RAP1B
NM_001010942
2029
TGACAGCGTGAGAGGTACTAGG
2030
CTGAGCCAAGAACGACTAGCTT
2031
CACGCATGATGCAAG
2032
TGACAGCGTGAGAGGTACTAGGTTTTGACAA









CTTGTCAAA

GCTTGCATCATGCGTGAGTATAAGCTAGTCG











TTCTTGGCTCA





RARB
NM_000965
2033
ATGAACCCTTGACCCCAAGT
2034
GAGCTGGGTGAGATGCTAGG
2035
TGTGCTCTGCTGTGT
2036
ATGAACCCTTGACCCCAAGTTCAAGTGGGAA









TCCCACTTG

CACAGCAGAGCACAGTCCTAGCATCTCACCC











AGCTC





RASSF1
NM_007182
2037
AGGGCACGTGAAGTCATTG
2038
AAAGAGTGCAAACTTGCGG
2039
CACCACCAAGAACTT
2040
AGGGCACGTGAAGTCATTGAGGCCCTGCTGC









TCGCAGCAG

GAAAGTTCTTGGTGGTGGATGACCCCCGCAA











GTTTGCACTCT





RB1
NM_000321
2041
CGAAGCCCTTACA
2042
GGACTCTTCAGGGGT
2043
CCCTTACGGATTCCT
2044
CGAAGCCCTTACAAGTTTCCTAGTTCACCCT









GGAGG

TACGGA





RECK
NM_021111
2045
GTCGCCGAGTGTG
2046
GTGGGATGATGGGTT
2047
TCAAGTGTCCTTCGC
2048
GTCGCCGAGTGTGCTTCTGTCAAGTGTCCTT









TCTTG

CGCTCT





REG4
NM_032044
2049
TGCTAACTCCTGCACAGCC
2050
TGCTAGGTTTCCCCTCTGAA
2051
TCCTCTTCCTTTCTGC
2052
TGCTAACTCCTGCACAGCCCCGTCCTCTTCC









TAGCCTGGC

TTTCTGCTAGCCTGGCTAAATCTGCTCATTA











TTTCAGAGGGGA





RELA
NM_021975
2053
CTGCCGGGATGGC
2054
CCAGGTTCTGGAAAC
2055
CTGAGCTCTGCCCGG
2056
CTGCCGGGATGGCTTCTATGAGGCTGAGCTC









ACCGC

TGCCC





RFX1
NM_002918
2057
TCCTCTCCAAGTTC
2058
CAGGCCCTGGTACAG
2059
TCCAATGGACCAAGC
2060
TCCTCTCCAAGTTCGAGCCCGTGCTCCAATG









ACTGT

GACCAA





RGS10
NM_001005339
2061
AGACATCCACGACAGCGAT
2062
CCATTTGGCTGTGCTCTTG
2063
AGTTCCAGCAGCAGC
2064
AGACATCCACGACAGCGATGGCAGTTCCAGC









CACCAGAG

AGCAGCCACCAGAGCCTCAAGAGCACAGCCA











AATGG





RGS7
NM_002924
2065
CAGGCTGCAGAGAGCATTT
2066
TTTGCTTGTGCTTCTGCTTG
2067
TGAAAATGAACTCCC
2068
CAGGCTGCAGAGAGCATTTGCCCGGAAGTGG









ACTTCCGGG

GAGTTCATTTTCATGCAAGCAGAAGCACAAG











CAAA





RHOA
NM_001664
2069
TGGCATAGCTCTG
2070
TGCCACAGCTGCATG
2071
AAATGGGCTCAACC
2072
TGGCATAGCTCTGGGGTGGGCAGTTTTTTGA









AGAAA

AAATG





RHOB
NM_004040
2073
AAGCATGAACAGG
2074
CCTCCCCAAGTCAGT
2075
CTTTCCAACCCCTGG
2076
AAGCATGAACAGGACTTGACCATCTTTCCAA









GGAAG

CCCCTG





RHOC
NM_175744
2077
CCCGTTCGGTCTG
2078
GAGCACTCAAGGTAG
2079
TCCGGTTCGCCATG
2080
CCCGTTCGGTCTGAGGAAGGCCGGGACATGG









TCCCG

CGAAC





RLN1
NM_006911
2081
AGCTGAAGGCAGCCCTATC
2082
TTGGAATCCTTTAATGCAGGT
2083
TGAGAGGCAACCATC
2084
AGCTGAAGGCAGCCCTATCTGAGAGGCAACC









ATTACCAGAGC

ATCATTACCAGAGCTACAGCAGTATGTACCT











GCATTAAAGG





RND3
NM_005168
2085
TCGGAATTGGACT
2086
CTGGTTACTCCCCTCC
2087
TTTTAAGCCTGACTC
2088
TCGGAATTGGACTTGGGAGGCGCGGTGAGGA









CTCAC

GTCAG





RNF114
NM_018683
2089
TGACAGGGGAAGT
2090
GGAAGACAGCTTTGG
2091
CCAGGTCAGCCCTTC
2092
TGACAGGGGAAGTGGGTCCCCAGGTCAGCCC









TCTTC

TTCTC





ROBO2
NM_002942
2093
CTACAAGGCCCAG
2094
CACCAGTGGCTTTAC
2095
CTGTACCATCCACTG
2096
CTACAAGGCCCAGCCAACCAAACGCTGGCAG









CCAGC

TGGAT





RRM1
NM_001033
2097
GGGCTACTGGCAG
2098
CTCTCAGCATCGGTA
2099
CATTGGATTGCCAT
2100
GGGCTACTGGCAGCTACATTGCTGGGACTAA









TAGTC

TGGCA





RRM2
NM_001034
2101
CAGCGGGATTAAA
2102
ATCTGCGTTGAAGCA
2103
CCAGCACAGCCAGTT
2104
CAGCGGGATTAAACAGTCCTTTAACCAGCAC









AAAAG

AGCCA





S100P
NM_005980
2105
AGACAAGGATGCC
2106
GAAGTCCACCTGGGC
2107
TTGCTCAAGGACCTG
2108
AGACAAGGATGCCGTGGATAAATTGCTCAAG









GACGC

GACCT





SAT1
NM_002970
2109
CCTTTTACCACTGC
2110
ACAATGCTGTGTCCTT
2111
TCCAGTGCTCTTTCG
2112
CCTTTTACCACTGCCTGGTTGCAGAAGTGCC









GCACT

GAAAGA





SCUBE2
NM_020974
2113
TGACAATCAGCACACCTGCAT
2114
TGTGACTACAGCCGTGATCCTTA
2115
CAGGCCCTCTTCCGA
2116
TGACAATCAGCACACCTGCATTCACCGCTCG









GCGGT

GAAGAGGGCCTGAGCTGCATGAATAAGGATC











ACGGCTGTAG





SDC1
NM_002997
2117
GAAATTGACGAGG
2118
AGGAGCTAACGGAGA
2119
CTCTGAGCGCCTCCA
2120
GAAATTGACGAGGGGTGTCTTGGGCAGAGCT









TCCAA

GGCTC





SDC2
NM_002998
2121
GGATTGAAGTGGC
2122
ACCAGCCACAGTACC
2123
AACTCCATCTCCTTC
2124
GGATTGAAGTGGCTGGAAAGAGTGATGCCTG









CCCAG

GGGAA





SDHC
NM_003001
2125
CTTCCCTCGGGTCT
2126
TTCCCTCCTGGTAAA
2127
TTACATCCTCCCTCT
2128
CTTCCCTCGGGTCTCAGGCATTTACATCCTC









CCCCG

CCTCTC





SEC14L1
NM_001039573
2129
AGGGTTCCCATGTGACCAG
2130
GCAGGCATGCTGTGGAAT
2131
CGGGCTTCTACATCC
2132
AGGGTTCCCATGTGACCAGGTGGCCGGGCTT









TGCAGTGG

CTACATCCTGCAGTGGAAATTCCACAGCATG











CCTGC





SEC23A
NM_006364
2133
CGTGTGCATTAGA
2134
CCCATTACCATGTATC
2135
TCCTGGAGATGAAAT
2136
CGTGTGCATTAGATCAGACAGGTCTCCTGGA









GCTGT

GATGA





SEMA3A
NM_006080
2137
TTGGAATGCAGTC
2138
CTCTTCATTTCGCCTC
2139
TTGCCAATAGACCAG
2140
TTGGAATGCAGTCCGAAGTCGCAGAGAGCGC









CGCTC

TGGTC





SEPT9
NM_006640
2141
CAGTGACCACGAG
2142
CTTCGATGGTACCCC
2143
TTGCCAATAGACCAG
2144
CAGTGACCACGAGTACCAGGTCAACGGCAAG









CGCTC

AGGAT





SERPINA3
NM_001085
2145
GTGTGGCCCTGTCTGCTTA
2146
CCCTGTGCATGTGAGAGCTAC
2147
AGGGAATCGCTGTCA
2148
GTGTGGCCCTGTCTGCTTATCCTTGGAAGGT









CCTTCCAAG

GACAGCGATTCCCTGTGTAGCTCTCACATGC











ACAGGG





SERPINB5
NM_002639
2149
CAGATGGCCACTTTGAGAACATT
2150
GGCAGCATTAACCACAAGGATT
2151
AGCTGACAACAGTGT
2152
CAGATGGCCACTTTGAGAACATTTTAGCTGA









GAACGACCAGACC

CAACAGTGTGAACGACCAGACCAAAATCCTT











GTGGTTAATG





SESN3
NM_144665
2153
GACCCTGGTTTTG
2154
GAGCTCGGAATGTTG
2155
TGCTCTTCTCCTCGT
2156
GACCCTGGTTTTGGGTATGAAGACTTTGCCA









CTGGC

GACGA





SFRP4
NM_003014
2157
TACAGGATGAGGC
2158
GTTGTTAGGGCAAGG
2159
CCTGGGACAGCCTAT
2160
TACAGGATGAGGCTGGGCATTGCCTGGGACA









GTAAG

GCCTA





SH3RF2
NM_152550
2161
CCATCACAACAGCCTTGAAC
2162
CACTGGGGTGCTGATCTCTA
2163
AACCGGATGGTCCAT
2164
CCATCACAACAGCCTTGAACACTCTCAACCG









TCTCCTTCA

GATGGTCCATTCTCCTTCAGGGCGCCATATG











GTAGAGATCAG





SH3YL1
NM_015677
2165
CCTCCAAAGCCAT
2166
CTTTGAGAGCCAGAG
2167
CACAGCAGTCATCTG
2168
CCTCCAAAGCCATTGTCAAGACCACAGCAGT









CACCA

CATCT





SHH
NM_000193
2169
GTCCAAGGCACAT
2170
GAAGCAGCCTCCCGA
2171
CACCGAGTTCTCTGC
2172
GTCCAAGGCACATATCCACTGCTCGGTGAAA









TTTCA

GCAGA





SHMT2
NM_005412
2173
AGCGGGTGCTAGA
2174
ATGGCACTTCGGTCT
2175
CCATCACTGCCAACA
2176
AGCGGGTGCTAGAGCTTGTATCCATCACTGC









AGAAC

CAACA





SIM2
NM_005069
2177
GATGGTAGGAAGG
2178
CACAAGGAGCTGTGA
2179
CGCCTCTCCACGCAC
2180
GATGGTAGGAAGGGATGTGCCCGCCTCTCCA









TCAGC

CGCAC





SIPA1L1
NM_015556
2181
CTAGGACAGCTTG
2182
CATAACCGTAGGGCT
2183
CGCCACAATGCCCTC
2184
CTAGGACAGCTTGGCTTCCATGTCAACTATG









ATAGT

AGGGC





SKIL
NM_005414
2185
AGAGGCTGAATAT
2186
CTATCGGCCTCAGCA
2187
CCAATCTCTGCCTCA
2188
AGAGGCTGAATATGCAGGACAGTTGGCAGAA









GTTCT

CTGAG





SLC22A3
NM_021977
2189
ATCGTCAGCGAGT
2190
CAGGATGGCTTGGGT
2191
CAGCATCCACGCATT
2192
ATCGTCAGCGAGTTTGACCTTGTCTGTGTCA









GACAC

ATGCGT





SLC25A21
NM_030631
2193
AAGTGTTTTTCCCCCTTGAGAT
2194
GGCCGATCGATAGTCTCTCTT
2195
TCATGGTGCTGCATA
2196
AAGTGTTTTTCCCCCTTGAGATAATGGATAT









GCAAATATCCA

TTGCTATGCAGCACCATGAAGAAGAGAGACT











ATCGATCGGCC





SLC44A1
NM_080546
2197
AGGACCGTAGCTG
2198
ATCCCATCCCAATGC
2199
TACCATGGCTGCTGC
2200
AGGACCGTAGCTGCACAGACATACCATGGCT









TCTTC

GCTGC





SMAD4
NM_005359
2201
GGACATTACTGGC
2202
ACCAATACTCAGGAG
2203
TGCATTCCAGCCTCC
2204
GGACATTACTGGCCTGTTCACAATGAGCTTG









CATTT

CATTCC





SMARCC2
NM_003075
2205
TACCGACTGAACCCCCAA
2206
GACATCACCCGCTAGGTTTC
2207
TATCTTACCTCTACC
2208
TACCGACTGAACCCCCAAGAGTATCTTACCT









GCCTGCCGC

CTACCGCCTGCCGCCGAAACCTAGCGGGTGA











TGTC





SMARCD1
NM_003076
2209
CCGAGTTAGCATATCCCAGG
2210
CCTTTGTGCCCAGCTGTC
2211
CCCACCCTTGCTGTG
2212
CCGAGTTAGCATATCCCAGGCTCGCAGACTC









TTGAGTCTG

AACACAGCAAGGGTGGGAGACAGCTGGGCAC











AAAGG





SMO
NM_005631
2213
GGCATCCAGTGCC
2214
CGCGATGTAGCTGTG
2215
CTTCACAGAGGCTGA
2216
GGCATCCAGTGCCAGAACCCGCTCTTCACAG









GCACC

AGGCT





SNAI1
NM_005985
2217
CCCAATCGGAAGC
2218
GTAGGGCTGCTGGAA
2219
TCTGGATTAGAGTCC
2220
CCCAATCGGAAGCCTAACTACAGCGAGCTGC









TGCAG

AGGAC





SNRPB2
NM_003092
2221
CGTTTCCTGCTTTT
2222
AGGTAGAAGGCGCAC
2223
CCCACCTAAGGCCTA
2224
CGTTTCCTGCTTTTGGTTCTTACAGTAGTCG









CGCCG

GCGTAG





SOD1
NM_000454
2225
TGAAGAGAGGCAT
2226
AATAGACACATCGGC
2227
TTTGTCAGCAGTCAC
2228
TGAAGAGAGGCATGTTGGAGACTTGGGCAAT









ATTGC

GTGAC





SORBS1
NM_015385
2229
GCAGATGAGTGGA
2230
AGCGAGTGAAGAGGG
2231
ATTTCCATTGGCATC
2232
GCAGATGAGTGGAGGCTTTCTTCCAGTGCTG









AGCAC

ATGCC





SOX4
NM_003107
2233
AGATGATCTCGGG
2234
GCGCCCTTCAGTAGG
2235
CGAGTCCAGCATCTC
2236
AGATGATCTCGGGAGACTGGCTCGAGTCCAG









CAACC

CATCT





SPARC
NM_003118
2237
TCTTCCCTGTACACTGGCAGTTC
2238
AGCTCGGTGTGGGAGAGGTA
2239
TGGACCAGCACCCCA
2240
TCTTCCCTGTACACTGGCAGTTCGGCCAGCT









TTGACGG

GGACCAGCACCCCATTGACGGGTACCTCTCC











CACACCGAGCT





SPARCL
NM_004684
2241
GGCACAGTGCAAG
2242
GATTGAGCTCTCTCG
2243
ACTTCATCCCAAGCC
2244
GGCACAGTGCAAGTGATGACTACTTCATCCC









AGGCC

AAGCC





SPDEF
NM_012391
2245
CCATCCGCCAGTATTACAAG
2246
GGGTGCACGAACTGGTAGA
2247
ATCATCCGGAAGCCA
2248
CCATCCGCCAGTATTACAAGAAGGGCATCAT









GACATCTCC

CCGGAAGCCAGACATCTCCCAGCGCCTCGTC











TACCAGTTCGT





SPINK1
NM_003122
2249
CTGCCATATGACC
2250
GTTGAAAACTGCACC
2251
ACCACGTCTCTTCAG
2252
CTGCCATATGACCCTTCCAGTCCCAGGCTTC









AAGCC

TGAAGA





SPINT1
NM_003710
2253
ATTCCCAGCACAG
2254
AGATGGCTACCACCA
2255
CTGTCGCAGTGTTCC
2256
ATTCCCAGCACAGGCTCTGTGGAGATGGCTG









TGGTC

TCGCA





SPP1
NM_001040058
2257
TCACACATGGAAAGCGAGG
2258
GTTCAGGTCCTGGGCAAC
2259
TGAATGGTGCATACA
2260
TCACACATGGAAAGCGAGGAGTTGAATGGTG









AGGCCATCC

CATACAAGGCCATCCCCGTTGCCCAGGACCT











GAAC





SQLE
NM_003129
2261
ATTTTCGAGGCCAAAAATC
2262
CCTGAGCAAGGATATTCACG
2263
TGGGCAAGAAAAACA
2264
ATTTTCGAGGCCAAAAAATCATTTTACTGGG









TCTCATTCCTTTG

CAAGAAAAACATCTCATTCCTTTGTCGTGAA











TATCCTTGCTC





SRC
NM_005417
2265
TGAGGAGTGGTATTTTGGCAAGA
2266
CTCTCGGGTTCTCTGCATTGA
2267
AACCGCTCTGACTCC
2268
TGAGGAGTGGTATTTTGGCAAGATCACCAGA









CGTCTGGTG

CGGGAGTCAGAGCGGTTACTGCTCAATGCAG











AGAACCCGAG





SRD5A1
NM_001047
2269
GGGCTGGAATCTG
2270
CCATGACTGCACAAT
2271
CCTCTCTCGGAGGCC
2272
GGGCTGGAATCTGTCTAGGAGCCCTCTCTCG









ACAGA

GAGGC





SRD5A2
NM_000348
2273
GTAGGTCTCCTGGCGTTCTG
2274
TCCCTGGAAGGGTAGGAGTAA
2275
AGACACCACTCAGAA
2276
GTAGGTCTCCTGGCGTTCTGCCAGCTGGCCT









TCCCCAGGC

GGGGATTCTGAGTGGTGTCTGCTTAGAGTTT











ACTCCTACCCTT





ST5
NM_005418
2277
CCTGTCCTGCCAG
2278
CAGCTGCACAAAACT
2279
AGTCACGAGCACCCA
2280
CCTGTCCTGCCAGAGCATGGATGAAGTTTCG









GCGA

CTGGGT





STAT1
NM_007315
2281
GGGCTCAGCTTTCAGAAGTG
2282
ACATGTTCAGCTGGTCCACA
2283
TGGCAGTTTTCTTCT
2284
GGGCTCAGCTTTCAGAAGTGCTGAGTTGGCA









GTCACCAAAA

GTTTTCTTCTGTCACCAAAAGAGGTCTCAAT











GTGGACCAGCT





STAT3
NM_003150
2285
TCACATGCCACTTT
2286
CTTGCAGGAAGCGGC
2287
TCCTGGGAGAGATTG
2288
TCACATGCCACTTTGGTGTTTCATAATCTCC









ACCAG

TGGGAG





STAT5A
NM_003152
2289
GAGGCGCTCAACATGAAATTC
2290
GCCAGGAACACGAGGTTCTC
2291
CGGTTGCTCTGCACT
2292
GAGGCGCTCAACATGAAATTCAAGGCCGAAG









TCGGCCT

TGCAGAGCAACCGGGGCCTGACCAAGGAGAA











CCTCGTGTTC





STAT5B
NM_012448
2293
CCAGTGGTGGTGA
2294
GCAAAAGCATTGTCC
2295
CAGCCAGGACAACAA
2296
CCAGTGGTGGTGATCGTTCATGGCAGCCAGG









TGCG

ACAAC





STMN1
NM_005563
2297
AATACCCAACGCA
2298
GGAGACAATGCAAAC
2299
CACGTTCTCTGCCCC
2300
AATACCCAACGCACAAATGACCGCACGTTCT









GTTTC

CTGCC





STS
NM_000351
2301
GAAGATCCCTTTCCTCCTACTGTT
2302
GGATGATGTTCGGCCTTGAT
2303
CTGCGTGGCTCTCGG
2304
GAAGATCCCTTTCCTCCTACTGTTCTTTCTGT





C



CTTCCCA

GGGAAGCCGAGAGCCACGCAGCATCAAGGCCG











AACATCATC





SULF1
NM_015170
2305
TGCAGTTGTAGGGAGTCTGG
2306
TCTCAAGAATTGCCGTTGAC
2307
TACCGTGCCAGCAGA
2308
TGCAGTTGTAGGGAGTCTGGTTACCGTGCCAG









AGCCAAAG

CAGAAGCCAAAGAAAGAGTCAACGGCAATTCT











TGAGA





SUMO1
NM_003352
2309
GTGAAGCCACCGT
2310
CCTTCCTTCTTATCCC
2311
CTGACCAGGAGGCAA
2312
GTGAAGCCACCGTCATCATGTCTGACCAGGA









AACCT

GGCAA





SVIL
NM_003174
2313
ACTTGCCCAGCAC
2314
GACACCATCCGTGTC
2315
ACCCCAGGACTGATG
2316
ACTTGCCCAGCACAAGGAAGACCCCAGGACT









TCAAG

GATGT





TAF2
NM_003184
2317
GCGCTCCACTCTCAGTCTTT
2318
CTTGTGCTCATGGTGATGGT
2319
AGCCTCCAAACACAG
2320
GCGCTCCACTCTCAGTCTTTACTAAGGAATC









TGACCACCA

TACAGCCTCCAAACACAGTGACCACCATCAC











CACCATCACCAT





TARP
NM_001003799
2321
GAGCAACACGATTCTGGGA
2322
GGCACCGTTAACCAGCTAAAT
2323
TCTTCATGGTGTTCC
2324
GAGCAACACGATTCTGGGATCCCAGGAGGGG









CCTCCTGG

AACACCATGAAGACTAACGACACATACATGA











AATTTAGCTG





TBP
NM_003194
2325
GCCCGAAACGCCG
2326
CGTGGCTCTCTTATCC
2327
TACCGCAGCAAACCG
2328
GCCCGAAACGCCGAATATAATCCCAAGCGGT









CTTGG

TTGCT





TFDP1
NM_007111
2329
TGCGAAGTGCTTTTGTTTGT
2330
GCCTTCCAGACAGTCTCCAT
2331
CGCACCAGCATGGCA
2332
TGCGAAGTGCTTTTGTTTGTTTGTTTTCGTT









ATAAGCTTT

TGGTTAAAGCTTATTGCCATGCTGGTGCGGC











TATGGAGACTGTC





TFF1
NM_003225
2333
GCCCTCCCAGTGTGCAAAT
2334
CGTCGATGGTATTAGGATAGAAGC
2335
TGCTGTTTCGACGAC
2336
GCCCTCCCAGTGTGCAAATAAGGGCTGCTGT







A

ACCGTTCG

TTCGACGACACCGTTCGTGGGGTCCCCTGGT











GCTTCTATCCTA





TFF3
NM_003226
2337
AGGCACTGTTCATCTCAGTTTTTC
2338
CATCAGGCTCCAGATATGAACTTT
2339
CAGAAGCGCTTGCCG
2340
AGGCACTGTTCATCTCAGCTTTTCTGTCCCT





T

C

GGAGCAAAGG

TTGCTCCCGGCAAGCGCTTCTGCTGAAAGTT











CATATCTGGAG





TGFA
NM_003236
2341
GGTGTGCCACAGACCTTCCT
2342
ACGGAGTTCTTGACAGAGTTTTGA
2343
TTGGCCTGTAATCAC
2344
GGTGTGCCACAGACCTTCTACTTGGCCTGTA









CTGTGCAGCCTT

ATCACCTGTGCAGCCTTTTGTGGGCCTTCAA











AACTCTGTCAA





TGFB1I1
NM_001042454
2345
GCTACTTTGAGCGCTTCTCG
2346
GGTCACCATCTTGTGTCGG
2347
CAAGATGTGGCTTCT
2348
GCTACTTTGAGCGCTTCTCGCCAAGATGTGG









GCAACCAGC

CTTCTGCAACCAGCCCATCCGACACAAGATG











GTGACC





TGFB2
NM_003238
2349
ACCAGTCCCCCAG
2350
CCTGGTGCTGTTGTA
2351
TCCTGAGCCCGAGGA
2352
ACCAGTCCCCCAGAAGACTATCCTGAGCCCG









AGTCC

AGGAA





TGFB3
NM_003239
2353
GGATCGAGCTCTT
2354
GCCACCGATATAGCG
2355
CGGCCAGATGAGCAC
2356
GGATCGAGCTCTTCCAGATCCTTCGGCCAGA









ATTGC

TGAGC





TGFBR2
NM_003242
2357
AACACCAATGGGT
2358
CCTCTTCATCAGGCC
2359
TTCTGGGCTCCTGAT
2360
AACACCAATGGGTTCCATCTTTCTGGGCTCC









TGCTC

TGATTG





THBS2
NM_003247
2361
CAAGACTGGCTACATCAGAGTCTT
2362
CAGCGTAGGTTTGGTCATAGATAG
2363
TGAGTCTGCCATGAC
2364
CAAGACTGGCTACATCAGAGTCTTAGTGCAT





AG

G

CTGTTTTCCTTCAT

GAAGGAAAACAGGTCATGGCAGACTCAGGAC











CTATCTATGA





THY1
NM_006288
2365
GGACAAGACCCTC
2366
TTGGAGGCTGTGGGT
2367
CAAGCTCCCAAGAGC
2368
GGACAAGACCCTCTCAGGCTGTCCCAAGCTC









TTCCA

CCAAG





TIAM1
NM_003253
2369
GTCCCTGGCTGAA
2370
GGGCTCCCGAAGTCT
2371
TGGAGCCCTTCTCCC
2372
GTCCCTGGCTGAAAATGGCCTGGAGCCCTTC









AAGAT

TCCCAA





TIMP2
NM_003255
2373
TCACCCTCTGTGA
2374
TGTGGTTCAGGCTCTT
2375
CCCTGGGACACCCTG
2376
TCACCCTCTGTGACTTCATCGTGCCCTGGGA









AGCAC

CACCCT





TIMP3
NM_000362
2377
CTACCTGCCTTGCT
2378
ACCGAAATTGGAGAG
2379
CCAAGAACGAGTGTC
2380
CTACCTGCCTTGCTTTGTGACTTCCAAGAAC









TCTGG

GAGTGT





TK1
NM_003258
2381
GCCGGGAAGACCGTAATTGT
2382
CAGCGGCACCAGGTTCAG
2383
CAAATGGCTTCCTCT
2384
GCCGGGAAGACCGTAATTGTGGCTGCACTGG









GGAAGGTCCCA

ATGGGACCTTCCAGAGGAAGCCATTTGGGGC











CATCCTGAAC





TMPRSS
NM_005656
2385
GGACAGTGTGCAC
2386
CTCCCACGAGGAAGG
2387
AAGCACTGTGCATCA
2388
GGACAGTGTGCACCTCAAAGACTAAGAAAGC









CCTTG

ACTGT





TMPRSS
DQ204772
2389
GAGGCGGAGGGCGAG
2390
ACTGGTCCTCACTCACAACT
2391
TAAGGCTTCCTGCCG
2392
GAGGCGGAGGCGGAGGGCGAGGGGCGGGGAG


2ERGA






CGCTCCA

CGCCGCCTGGAGCGCGGCAGGAAGCCTTATC











AGTTGTGAG





TMPRSS
DQ204773
2393
GAGGCGGAGGGCGAG
2394
TTCCTCGGGTCTCCAAAGAT
2395
CCTGGAATAACCTGC
2396
GAGGCGGAGGGCGAGGGGCGGGGAGCGCCGC


2ERGB






CGCGC

CTGGAGCGCGGCAGGTTATTCCAGGATCTTT











GGAGACCCG





TNF
NM_000594
2397
GGAGAAGGGTGAC
2398
TGCCCAGACTCGGCA
2399
CGCTGAGATCAATCG
2400
GGAGAAGGGTGACCGACTCAGCGCTGAGATC









GCCCG

AATCG





TNFRSF1
NM_003844
2401
TGCACAGAGGGTGTGGGTTAC
2402
TCTTCATCTGATTTACAAGCTGTA
2403
CAATGCTTCCAACAA
2404
TGCACAGAGGGTGTGGGTTACACCAATGCTT


0A




CATG

TTTGTTTGCTTGCC

CCAACAATTTGTTTGCTTGCCTCCCATGTAC











AGCTTGTAAAT





TNFRSF1
NM_003842
2405
CTCTGAGACAGTGCTTCGATGACT
2406
CCATGAGGCCCAACTTCCT
2407
CAGACTTGGTGCCCT
2408
CTCTGAGACAGTGCTTCGATGACTTTGCAGA


0B






TTGACTCC

CTTGGTGCCCTTTGACTCCTGGGAGCCGCTC











ATGAGGAAGTT





TNFRSF18
NM_148901
2409
CAGAAGCTGCCAGTTCCC
2410
CACCCACAGGTCTCCCAG
2411
CCTTCTCCTCTGCCG
2412
CAGAAGCTGCCAGTTCCCCGAGGAAGAGCGG









ATCGCTC

GGCGAGCGATCGGCAGAGGAGAAGGGGCGGC











TGGGAGACCT





TNFSF10
NM_003810
2413
CTTCACAGTGCTC
2414
CATCTGCTTCAGCTCG
2415
AAGTACACGTAAGTT
2416
CTTCACAGTGCTCCTGCAGTCTCTCTGTGTG









ACAGC

GCTGTA





TNFSF11
NM_003701
2417
AACTGCATGTGGG
2418
TGACACCCTCTCCACT
2419
ACATGACCAGGGACC
2420
AACTGCATGTGGGCTATGGGAGGGGTTGGTC









AACCC

CCTGG





TOP2A
NM_001067
2421
AATCCAAGGGGGA
2422
GTACAGATTTTGCCC
2423
CATATGGACTTTGAC
2424
AATCCAAGGGGGAGAGTGATGACTTCCATAT









TCAGC

GGACT





TP53
NM_000546
2425
CTTTGAACCCTTGC
2426
CCCGGGACAAAGCAA
2427
AAGTCCTGGGTGCTT
2428
CTTTGAACCCTTGCTTTGCAATAGGTGTGCG









CTGAC

TCAGAAG





TP63
NM_003722
2429
CCCCAAGCAGTGC
2430
GAATCGCACAGCATC
2431
CCCGGGTCTCACTGG
2432
CCCCAAGCAGTGCCTCTACAGTCAGTGTGGG









AGCCC

CTCCA





TPD52
NM_005079
2433
GCCTGTGAGATTC
2434
ATGTGCTTGGACCTC
2435
TCTGCTACCCACTGC
2436
GCCTGTGAGATTCCTACCTTTGTTCTGCTAC









CAGAT

CCACTG





TPM1
NM_001018005
2437
TCTCTGAGCTCTGCATTTGTC
2438
GGCTCTAAGGCAGGATGCTA
2439
TTCTCCAGCTGACCC
2440
TCTCTGAGCTCTGCATTTGTCTATTCTCCAG









TGGTTCTCTC

CTGACCCTGGTTCTCTCTCTTAGCATCCTGC











CTTAGAGCC





TPM2
NM_213674
2441
AGGAGATGCAGCT
2442
CCACCTCTTCATATTT
2443
CCAAGCACATCGCTG
2444
AGGAGATGCAGCTGAAGGAGGCCAAGCACAT









AGGAT

CGCTG





TPP2
NM_003291
2445
TAACCGTGGCATC
2446
ATGCCAACGCCATGA
2447
ATCCTGTTCAGGTGG
2448
TAACCGTGGCATCTACCTCCGAGATCCTGTT









CTGCA

CAGGTG





TPX2
NM_012112
2449
TCAGCTGTGAGCTGCGGATA
2450
ACGGTCCTAGGTTTGAGGTTAAGA
2451
CAGGTCCCATTGCCG
2452
TCAGCTGTGAGCTGCGGATACCGCCCGGCAA









GGCG

TGGGACCTGCTCTTAACCTCAAACCTAGGAC











CGT





TRA2A
NM_013293
2453
GCAAATCCAGATC
2454
CTTCACGAAGATCCC
2455
AACTGAGGCCAAACA
2456
GCAAATCCAGATCCCAACACTTGCCTTGGAG









CTCCA

TGTTTG





TRAF3IP
NM_147200
2457
CCTCACAGGAACC
2458
CTGGGGCTGGGAATC
2459
TGGATCTGCCAACCA
2460
CCTCACAGGAACCGAGCAGGCCTGGATCTGC









TAGAC

CAACC





TRAM1
NM_014294
2461
CAAGAAAAGCACC
2462
ATGTCCGCGTGATTCT
2463
AGTGCTGAGCCACGA
2464
CAAGAAAAGCACCAAGAGCCCCCCAGTGCTG









ATTCG

AGCCA





TRAP1
NM_016292
2465
TTACCAGTGGCTTT
2466
TGTCCCGGTTCTAACT
2467
TTCGGCGATTTCAAA
2468
TTACCAGTGGCTTTCAGATGGTTCTGGAGTG









CACTC

TTTGAA





TRIM14
NM_033220
2469
CATTCGCCTTAAG
2470
CAAGGTACCTGGCTT
2471
AACTGCCAGCTCTCA
2472
CATTCGCCTTAAGGAAAGCATAAACTGCCAG









GACCC

CTCTCA





TRO
NM_177556
2473
GCAACTGCCACCC
2474
TGGTGTGGATACTGG
2475
CCACCCAAGGCCAAA
2476
GCAACTGCCACCCATACAGCTACCACCCAAG









TTACC

GCCAA





TRPC6
NM_004621
2477
CGAGAGCCAGGACTATCTGC
2478
TAGCCGTAGCAAGGCAGC
2479
CTTCTCCCAGCTCCG
2480
CGAGAGCCAGGACTATCTGCTCATGGACTCG









AGTCCATG

GAGCTGGGAGAAGACGGCTGCCCGCAAGCCC











CGCTGCCTTG





TRPV6
NM_018646
2481
CCGTAGTCCCTGCAACCTC
2482
TCCTCACTGTTCACACAGGC
2483
ACTTTGGGGAGCACC
2484
CCGTAGTCCCTGCAACCTCATCTACTTTGGG









CTTTGTCCT

GAGCACCCTTTGTCCTTTGCTGCCTGTGTGA











ACAGTGAGGA





TSTA3
NM_003313
2485
CAATTTGGACTTCT
2486
CACCTCAAAGGCCGA
2487
AACGTGCACATGAAC
2488
CAATTTGGACTTCTGGAGGAAAAACGTGCAC









GACAA

ATGAA





TUBB2A
NM_001069
2489
CGAGGACGAGGCT
2490
ACCATGCTTGAGGAC
2491
TCTCAGATCAATCGT
2492
CGAGGACGAGGCTTAAAAACTTCTCAGATCA









GCATC

ATCGT





TYMP
NM_001953
2493
CTATATGCAGCCAGAGATGTGACA
2494
CCACGAGTTTCTTACTGAGAATGG
2495
ACAGCCTGCCACTCA
2496
CTATATGCAGCCAGAGATGTGACAGCCACCG









TCACAGCC

TGGACAGCCTGCCACTCATCACAGCCTCCAT











TCTCAGTAAGA





TYMS
NM_001071
2497
GCCTCGGTGTGCC
2498
CGTGATGTGCGCAAT
2499
CATCGCCAGCTACGC
2500
GCCTCGGTGTGCCTTTCAACATCGCCAGCTA









CCTGC

CGCCCT





UAP1
NM_003115
2501
CTGGAGACGGTCGTAGCTG
2502
GCCAAGCTTTGTAGAAATAGGG
2503
TACCTGTAAACCTTT
2504
CTGGAGACGGTCGTAGCTGCGGTCGCGCCGA









CTCGGCGCG

GAAAGGTTTACAGGTACATACATTACACCCC











TATTTCTACAA





UBE2C
NM_007019
2505
TGTCTGGCGATAA
2506
ATGGTCCCTACCCATT
2507
TCTGCCTTCCCTGAA
2508
TGTCTGGCGATAAAGGGATTTCTGCCTTCCC









TCAGA

TGAATC





UBE2G1
NM_003342
2509
TGACACTGAACGA
2510
AAGCAGAGAGGAATC
2511
TTGTCCCACCAGTGC
2512
TGACACTGAACGAGGTGGCTTTTGTCCCACC









CTCAT

AGTGCC





UBE2T
NM_014176
2513
TGTTCTCAAATTGC
2514
AGAGGTCAACACAGT
2515
AGGTGCTTGGAGACC
2516
TGTTCTCAAATTGCCACCAAAAGGTGCTTGG









ATCCC

AGACC





UGDH
NM_003359
2517
GAAACTCCAGAGG
2518
CTCTGGGAACCCAGT
2519
TATACAGCACACAGG
2520
GAAACTCCAGAGGGCCAGAGAGCTGTGCAGG









GCCTG

CCCTG





UGT2B1
NM_001076
2521
AAGCCTGAAGTGG
2522
CCTCCATTTAAAACCC
2523
AAAGATGGGACTCCT
2524
AAGCCTGAAGTGGAATGACTGAAAGATGGGA









CCTTT

CTCCT





UGT2B1
NM_001077
2525
TTGAGTTTGTCATG
2526
TCCAGGTGAGGTTGT
2527
ACCCGAAGGTGCTTG
2528
TTGAGTTTGTCATGCGCCATAAAGGAGCCAA









GCTCC

GCACC





UHRF1
NM_013282
2529
CTACAGGGGCAAA
2530
GGTGTCATTCAGGCG
2531
CGGCCATACCCTCTT
2532
CTACAGGGGCAAACAGATGGAGGACGGCCAT









CGACT

ACCCT





UTP23
NM_032334
2533
GATTGCACAAAAA
2534
GGAAAGCAGACATTC
2535
TCGAAATTGTCCTCA
2536
GATTGCACAAAAATGCCAAGTTCGAAATTGT









TTTCA

CCTCAT





VCAM1
NM_001078
2537
TGGCTTCAGGAGCTGAATACC
2538
TGCTGTCGTGATGAGAAAATAGTG
2539
CAGGCACACACAGG
2540
TGGCTTCAGGAGCTGAATACCCTCCCAGGCA









TGGGACACAAAT

CACACAGGTGGGACACAAATAAGGGTTTTGG











AACCACTATT





VCL
NM_003373
2541
GATACCACAACTCCCATCAAGCT
2542
TCCCTGTTAGGCGCATCAG
2543
AGTGGCAGCCACGGC
2544
GATACCACAACTCCCATCAAGCTGTTGGCAG









GCC

TGGCAGCCACGGCGCCTCCTGATGCGCCTAA











CAGGGA





VCPIP1
NM_250054
2545
TTTCTCCCAGTACC
2546
TGAATAGGGAGCCTT
2547
TGGTCCATCCTCTGC
2548
TTTCTCCCAGTACCATTCGTGATGGTCCATC









ACCTG

CTCTGC





VDR
NM_000376
2549
CCTCTCCTTCCAGC
2550
TCATTGCCAAACACTT
2551
CAGCATGAAGCTAAC
2552
CCTCTCCTTCCAGCCTGAGTGCAGCATGAAG









GCCCC

CTAACG





VEGFA
NM_003376
2553
CTGCTGTCTTGGG
2554
GCAGCCTGGGACCAC
2555
TTGCCTTGCTGCTCT
2556
CTGCTGTCTTGGGTGCATTGGAGCCTTGCCT









ACCTC

TGCTGC





VEGFB
NM_003377
2557
TGACGATGGCCTG
2558
GGTACCGGATCATGA
2559
CTGGGCAGCACCAAG
2560
TGACGATGGCCTGGAGTGTGTGCCCACTGGG









TCCGG

CAGCA





VEGFC
NM_005429
2561
CCTCAGCAAGACGTTATTTGAAAT
2562
AAGTGTGATTGGCAAAACTGATTG
2563
CCTCTCTCTCAAGGC
2564
CCTCAGCAAGACGTTATTTGAAATTACAGTG





T



CCCAAACCAGT

CCTCTCTCTCAAGGCCCCAAACCAGTAACAA











TCAGTTTTGCCA





VIM
NM_003380
2565
TGCCCTTAAAGGA
2566
GCTTCAACGGCAAAG
2567
ATTTCACGCATCTGG
2568
TGCCTTAAAGGAACCAATGAGTCCCTGGAAC









CGTTC

GCCA





VTI1B
NM_006370
2569
ACGTTATGCACCCCTGTCTT
2570
CCGATGGAGTTTAGCAAGGT
2571
CGAAACCCCATGATG
2572
ACGTTATGCACCCCTGTCTTTCCGAAACCCC









TCTAAGCTTCG

ATGATGTCTAAGCTTCGAAACTACCGGAAGG











ACCTTGCTAAA





WDR19
NM_025132
2573
GAGTGGCCCAGAT
2574
GATGCTTGAGGGCTT
2575
CCCCTCGACGTATGT
2576
GAGTGGCCCAGATGTCCATAAGAATGGGAGA









CTCCC

CATAC





WFDC1
NM_021197
2577
ACCCCTGCTCTGT
2578
ATACCTTCGGCCACG
2579
CTATGAGTGCCACAT
2580
ACCCCTGCTCTGTCCCTCGGGCTATGAGTGC









CCTGA

CACATC





WISP1
NM_003882
2581
AGAGGCATCCATGAACTTCACA
2582
CAAACTCCACAGTACTTGGGTTGA
2583
CGGGCTGCATCAGCA
2584
AGAGGCATCCATGAACTTCACACTTGCGGGC









CACGC

TGCATCAGCACACGCTCCTATCAACCCAAGT











ACTGTGGAGTT





WNT5A
NM_003392
2585
GTATCAGGACCACATGCAGTACAT
2586
TGTCGGAATTGATACTGGCATT
2587
TTGATGCCTGTCTTC
2588
GTATCAGGACCACATGCAGTACATCGGAGAA





C



GCGCCTTCT

GGCGCGAAGACAGGCATCAAAGAATGCCAGT











ATCAATTCCG





WWOX
NM_016373
2589
ATCGCAGCTGGTG
2590
AGCTCCCTGTTGCAT
2591
CTGCTGTTTACCTTG
2592
ATCGCAGCTGGTGGGTGTACACACTGCTGTT









GCGAG

TACCTT





XIAP
NM_001167
2593
GCAGTTGGAAGACACAGGAAAGT
2594
TGCGTGGCACTATTTTCAAGA
2595
TCCCCAAATTGCAGA
2596
GCAGTTGGAAGACACAGGAAAGTATCCCCAA









TTTATCAACGGC

ATTGCAGATTTATCAACGGCTTTTATCTTGA











AAATAGTGCCA





XRCC5
NM_021141
2597
AGCCCACTTCAGC
2598
AGCAGGATTCACACT
2599
TCTGGCTGAAGGCAG
2600
AGCCCACTTCAGCGTCTCCAGTCTGGCTGAA









TGTCA

GGCAG





YY1
NM_003403
2601
ACCCGGGCAACAA
2602
GACCGAGAACTCGCC
2603
TTGATCTGCACCTGC
2604
ACCCGGGCAACAAGAAGTGGGAGCAGAAGCA









TTCTG

GGTGC





ZFHX3
NM_006885
2605
CTGTGGAGCCTCT
2606
GGAGCAGGGTTGGAT
2607
ACCTGGCCCAACTCT
2608
CTGTGGAGCCTCTGCCTGCGGACCTGGCCCA









ACCAG

ACTCTA





ZFP36
NM_003407
2609
CATTAACCCACTC
2610
CCCCCACCATCATGA
2611
CAGGTCCCCAAGTGT
2612
CATTAACCCACTCCCCTGACCTCACGCTGGG









GCAAG

GCAGGT





ZMYND8
NM_183047
2613
GGTCTGGGCCAAA
2614
TGCCCGTCTTTATCCC
2615
CTTTTGCAGGCCAGA
2616
GGTCTGGGCCAAACTGAAGGGGTTTCCATTC









ATGGA

TGGCCT





ZNF3
NM_017715
2617
CGAAGGGACTCTG
2618
GCAGGAGGTCCTCAG
2619
AGGAGGTTCCACACT
2620
CGAAGGGACTCTGCTCCAGTGAACTGGCGAG









CGCCA

TGTGG





ZNF827
NM_178835
2621
TGCCTGAGGACCC
2622
GAGGTGGCGGAGTGA
2623
CCCGCCTTCAGAGAA
2624
TGCCTGAGGACCCTCTACCGCCCCCGCCTTC









GAAAC

AGAGA





ZWINT
NM_007057
2625
TAGAGGCCATCAA
2626
TCCGTTTCCTCTGGGC
2627
ACCAAGGCCCTGACT
2628
TAGAGGCCATCAAAATTGGCCTCACCAAGGC









CAGAT

CCTGA


















TABLE B







SEQ


microRNA
Sequence
ID NO







hsa-miR-1
UGGAAUGUAAAGAAGUAUGUAU
2629





hsa-miR-103
GCAGCAUUGUACAGGGCUAUGA
2630





hsa-miR-106b
UAAAGUGCUGACAGUGCAGAU
2631





hsa-miR-10a
UACCCUGUAGAUCCGAAUUUGUG
2632





hsa-miR-133a
UUUGGUCCCCUUCAACCAGCUG
2633





hsa-miR-141
UAACACUGUCUGGUAAAGAUGG
2634





hsa-miR-145
GUCCAGUUUUCCCAGGAAUCCCU
2635





hsa-miR-146b-5p
UGAGAACUGAAUUCCAUAGGCU
2636





hsa-miR-150
UCUCCCAACCCUUGUACCAGUG
2637





hsa-miR-152
UCAGUGCAUGACAGAACUUGG
2638





hsa-miR-155
UUAAUGCUAAUCGUGAUAGGGGU
2639





hsa-miR-182
UUUGGCAAUGGUAGAACUCACACU
2640





hsa-miR-191
CAACGGAAUCCCAAAAGCAGCUG
2641





hsa-miR-19b
UGUAAACAUCCUCGACUGGAAG
2642





hsa-miR-200c
UAAUACUGCCGGGUAAUGAUGGA
2643





hsa-miR-205
UCCUUCAUUCCACCGGAGUCUG
2644





hsa-miR-206
UGGAAUGUAAGGAAGUGUGUGG
2645





hsa-miR-21
UAGCUUAUCAGACUGAUGUUGA
2646





hsa-miR-210
CUGUGCGUGUGACAGCGGCUGA
2647





hsa-miR-22
AAGCUGCCAGUUGAAGAACUGU
2648





hsa-miR-222
AGCUACAUCUGGCUACUGGGU
2649





hsa-miR-26a
UUCAAGUAAUCCAGGAUAGGCU
2650





hsa-miR-27a
UUCACAGUGGCUAAGUUCCGC
2651





hsa-miR-27b
UUCACAGUGGCUAAGUUCUGC
2652





hsa-miR-29b
UAGCACCAUUUGAAAUCAGUGUU
2653





hsa-miR-30a
CUUUCAGUCGGAUGUUUGCAGC
2654





hsa-miR-30e-5p
CUUUCAGUCGGAUGUUUACAGC
2655





hsa-miR-31
AGGCAAGAUGCUGGCAUAGCU
2656





hsa-miR-331
GCCCCUGGGCCUAUCCUAGAA
2657





hsa-miR-425
AAUGACACGAUCACUCCCGUUGA
2658





hsa-miR-449a
UGGCAGUGUAUUGUUAGCUGGU
2659





hsa-miR-486-5p
UCCUGUACUGAGCUGCCCCGAG
2660





hsa-miR-92a
UAUUGCACUUGUCCCGGCCUGU
2661





hsa-miR-93
CAAAGUGCUGUUCGUGCAGGUAG
2662





hsa-miR-99a
AACCCGUAGAUCCGAUCUUGUG
2663








Claims
  • 1. 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 consisting 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.
  • 2. The method of claim 1, wherein the at least one reference gene comprises one or more of AAMP, ARF1, ATP5E, CLTC, EEF1A1, GPS1, GPX1, and PGK1.
  • 3. The method of claim 1, wherein the at least one reference gene is selected from the group consisting of AAMP, ARF1, ATP5E, CLTC, EEF1A1, GPS1, GPX1, and PGK1.
  • 4. The method of claim 1, wherein the tissue sample has a positive TMPRSS2 fusion status.
  • 5. The method of claim 1, wherein the tissue sample has a negative TMPRSS2 fusion status.
  • 6. The method of claim 1, wherein the patient has early-stage prostate cancer.
  • 7. The method of claim 1, wherein the tissue sample comprises prostate tumor tissue with the primary Gleason pattern for the patient's prostate tumor.
  • 8. The method of claim 1, wherein the tissue sample comprises prostate tumor tissue with the highest Gleason pattern for the patient's prostate tumor.
  • 9. The method of claim 1, wherein the tissue sample comprises non-tumor prostate tissue.
  • 10. The method of claim 1, wherein the patient is receiving active surveillance treatment.
  • 11. The method of claim 1, wherein the at least one reference gene consists of from 1 to 6 reference genes.
Parent Case Info

This application is a continuation of U.S. patent application Ser. No. 13/190,391, filed Jul. 25, 2011, and 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 in their entirety.

US Referenced Citations (101)
Number Name Date Kind
5712097 Kern et al. Jan 1998 A
6190857 Ralph et al. Feb 2001 B1
6300060 Kantoff et al. Oct 2001 B1
6692916 Bevilacqua et al. Feb 2004 B2
RE38490 Thompson Apr 2004 E
6960439 Bevilacqua et al. Nov 2005 B2
6964850 Bevilacqua et al. Nov 2005 B2
7018837 Filvaroff et al. Mar 2006 B2
7022474 Nezu et al. Apr 2006 B2
7229774 Chinnaiyan et al. Jun 2007 B2
7695913 Cowens et al. Apr 2010 B2
7943306 Chang et al. May 2011 B2
7957909 Bevilacqua et al. Jun 2011 B2
8067178 Baker et al. Nov 2011 B2
8114597 Liew Feb 2012 B2
20020173461 Pennica Nov 2002 A1
20030017513 Khosravi et al. Jan 2003 A1
20030087818 Jiang et al. May 2003 A1
20030113743 Slawin et al. Jun 2003 A1
20030138793 Su et al. Jul 2003 A1
20030148410 Berger et al. Aug 2003 A1
20030170713 Srivastava et al. Sep 2003 A1
20030198970 Roberts Oct 2003 A1
20030207808 Savitzky et al. Nov 2003 A1
20030215835 Sun et al. Nov 2003 A1
20040053317 Glinskii Mar 2004 A1
20040203012 Diamandis Oct 2004 A1
20050048542 Baker et al. Mar 2005 A1
20050112705 Bracco et al. May 2005 A1
20050191673 Schlegel et al. Sep 2005 A1
20050260646 Baker et al. Nov 2005 A1
20050282170 Fradet et al. Dec 2005 A1
20060051763 Loukola et al. Mar 2006 A1
20060088823 Haab et al. Apr 2006 A1
20060166230 Baker et al. Jul 2006 A1
20060281122 Bryant et al. Dec 2006 A1
20060292572 Stuart et al. Dec 2006 A1
20060292610 Shen et al. Dec 2006 A1
20070048738 Donkena et al. Mar 2007 A1
20070059697 Strovel et al. Mar 2007 A1
20070099209 Clarke et al. May 2007 A1
20070105133 Clarke et al. May 2007 A1
20070212702 Tomlins et al. Sep 2007 A1
20070218512 Strongin et al. Sep 2007 A1
20070224596 Nacht et al. Sep 2007 A1
20070253953 Chen et al. Nov 2007 A1
20070275398 Kiefer et al. Nov 2007 A1
20080015448 Keely et al. Jan 2008 A1
20080131887 Stephan et al. Jun 2008 A1
20080171352 Goix et al. Jul 2008 A1
20080213791 Freije et al. Sep 2008 A1
20080222741 Chinnaiyan Sep 2008 A1
20080254481 Love et al. Oct 2008 A1
20080269064 Ramael Oct 2008 A1
20080275652 Sotiriou et al. Nov 2008 A1
20090023149 Knudsen Jan 2009 A1
20090047694 Shuber Feb 2009 A1
20090048266 Heise et al. Feb 2009 A1
20090098538 Glinsky Apr 2009 A1
20090123439 Yun et al. May 2009 A1
20090142262 Salceda et al. Jun 2009 A1
20090170075 Petrovics et al. Jul 2009 A1
20090215709 Van Criekinge et al. Aug 2009 A1
20090233279 Glinskii Sep 2009 A1
20090258795 Cowens et al. Oct 2009 A1
20090297525 Depinho et al. Dec 2009 A1
20090298082 Klee et al. Dec 2009 A1
20090305277 Baker et al. Dec 2009 A1
20090318775 Michelson et al. Dec 2009 A1
20100015620 Strovel et al. Jan 2010 A1
20100048414 Weaver et al. Feb 2010 A1
20100113290 Klass et al. May 2010 A1
20100120788 Wang et al. May 2010 A1
20100124745 Liew May 2010 A1
20100130377 Vasmatzis et al. May 2010 A1
20100143247 Fenske et al. Jun 2010 A1
20100227317 Thomson Okatsu Sep 2010 A1
20100233187 Chan et al. Sep 2010 A1
20100233732 Bates et al. Sep 2010 A1
20100233961 Holden et al. Sep 2010 A1
20100267032 Baker et al. Oct 2010 A1
20100291573 Cowens et al. Nov 2010 A1
20100293130 Stephan et al. Nov 2010 A1
20100297657 Chinnaiyan Nov 2010 A1
20100303795 Sorensen Dec 2010 A1
20110039269 Cowens et al. Feb 2011 A1
20110039271 Cowens et al. Feb 2011 A1
20110059447 Liew Mar 2011 A1
20110097759 Cowens et al. Apr 2011 A1
20110111421 Cowens et al. May 2011 A1
20110123990 Baker et al. May 2011 A1
20110124003 Ralph May 2011 A1
20110136683 Davicioni Jun 2011 A1
20110153534 Chudin et al. Jun 2011 A1
20110171633 Cowens et al. Jul 2011 A1
20110236903 McClelland et al. Sep 2011 A1
20110265197 Depinho et al. Oct 2011 A1
20120028264 Shak et al. Feb 2012 A1
20120040842 Baker et al. Feb 2012 A1
20120136583 Lazar et al. May 2012 A1
20120171688 Cowens et al. Jul 2012 A1
Foreign Referenced Citations (86)
Number Date Country
2005211023 Aug 2005 JP
WO-9700449 Jan 1997 WO
WO-9802748 Jan 1998 WO
WO-9904238 Jan 1999 WO
WO-9945398 Sep 1999 WO
WO-9964626 Dec 1999 WO
WO-9964627 Dec 1999 WO
0050899 Aug 2000 WO
WO-0050899 Aug 2000 WO
WO-0136674 May 2001 WO
WO-0231209 Apr 2002 WO
WO-0237113 May 2002 WO
WO-03050243 Jun 2003 WO
2003053223 Jul 2003 WO
03089932 Oct 2003 WO
WO-03089932 Oct 2003 WO
WO-2004053106 Jun 2004 WO
WO-2004077942 Sep 2004 WO
2014108896 Dec 2004 WO
WO-2005008213 Jan 2005 WO
WO-2005012875 Feb 2005 WO
WO-2005068655 Jul 2005 WO
WO-2005076005 Aug 2005 WO
WO-2005083128 Sep 2005 WO
WO-2005117943 Dec 2005 WO
WO-2005119260 Dec 2005 WO
WO-2006005043 Jan 2006 WO
WO-2006028655 Mar 2006 WO
WO-2006066240 Jun 2006 WO
WO-2006105642 Oct 2006 WO
WO-2006124836 Nov 2006 WO
WO-2007070621 Jun 2007 WO
WO-2007072225 Jun 2007 WO
WO-2007075672 Jul 2007 WO
WO-2007082099 Jul 2007 WO
WO-2007140352 Dec 2007 WO
WO-2008036717 Mar 2008 WO
WO-2008046510 Apr 2008 WO
WO-2008048570 Apr 2008 WO
WO-2008067065 Jun 2008 WO
WO-2008077165 Jul 2008 WO
WO-2008122447 Oct 2008 WO
WO-2008141275 Nov 2008 WO
WO-2008153743 Dec 2008 WO
WO-2009021338 Feb 2009 WO
WO-2009049966 Apr 2009 WO
WO-2009051734 Apr 2009 WO
WO-2009056862 May 2009 WO
WO-2009068409 Jun 2009 WO
WO-2009068423 Jun 2009 WO
WO-2009070767 Jun 2009 WO
WO-2009089521 Jul 2009 WO
WO-2009105154 Aug 2009 WO
WO-2009105640 Aug 2009 WO
WO-2009118204 Oct 2009 WO
WO-2009124251 Oct 2009 WO
WO-2009126122 Oct 2009 WO
WO-2009132257 Oct 2009 WO
WO-2009138392 Nov 2009 WO
WO-2009139915 Nov 2009 WO
WO-2009140741 Nov 2009 WO
WO-2009143603 Dec 2009 WO
WO-2009144460 Dec 2009 WO
WO-2009149166 Dec 2009 WO
WO-2010003773 Jan 2010 WO
WO-2010006048 Jan 2010 WO
WO-2010009337 Jan 2010 WO
WO-2010011310 Jan 2010 WO
WO-2010028820 Mar 2010 WO
WO-2010046530 Apr 2010 WO
WO-2010048278 Apr 2010 WO
WO-2010056351 May 2010 WO
WO-2010056993 May 2010 WO
WO-2010063454 Jun 2010 WO
WO-2010065940 Jun 2010 WO
WO-2010080702 Jul 2010 WO
WO-2010080933 Jul 2010 WO
WO-2010083252 Jul 2010 WO
WO-2010086389 Aug 2010 WO
WO-2010096734 Aug 2010 WO
WO-2010099577 Sep 2010 WO
WO-2010118520 Oct 2010 WO
WO-2010119126 Oct 2010 WO
WO-2010127399 Nov 2010 WO
WO-2010129965 Nov 2010 WO
WO-2011039734 Apr 2011 WO
Non-Patent Literature Citations (110)
Entry
Whitehead (Genome Biology 2005 vol. 6 Issue 2 Article R13).
Nakagawa (PloS ONE May 2008 vol. 3 Issue 5 e2318 pp. 1-14).
Lapointe (PNAS Jan. 20, 2004 vol. 101 No. 3 pp. 811-816).
Edwards (British Journal of Cancer 2005 vol. 92 pp. 376-381).
Erickson (Nature Protocols vol. 4 No. 6 May 21, 2009 pp. 902-922).
Tomlins (Nature Genetics vol. 39 No. Jan. 1, 2007 pp. 41-51).
Singh (Cancer Letters 237 vol. 2006 pp. 298-304).
Barwick (British Journal of Cancer Jan. 12, 2010 vol. 102 pp. 570-576).
Ornish (PNAS Jun. 17, 2008 vol. 105 No. 24 pp. 8369-8374).
Cheville (Journal of Clinical Oncology vol. 26 No. 24 Aug. 20, 2008 pp. 3930-3936).
International Search Report and Written Opinion for Application No. PCT/US2013/023409, dated Jun. 7, 2013, 12 pages.
Nishidate T., et al., “Genome-wide Gene-expression Profiles of Breast-cancer Cells Purified with Laser Microbeam Microdissection: Identification of Genes Associated with Progression and Metastasis,” International Journal of Oncology, 2004, vol. 25 (4), pp. 797-819.
Peters D., et al., “Genome-Wide Transcriptional Analysis of Carboplatin Response in Chemosensitive and Chemoresistant Ovarian Cancer Cells,” Molecular Cancer Therapeutics, 2005, vol. 4 (10), pp. 1605-1616.
Shen R., et al., “Prognostic Meta-signature of Breast Cancer Developed by Two-stage Mixture Modeling of Microarray Data,” BMC Genomics, 2004, vol. 5 (1), pp. 94.
Taioli E., et al., “Multi-institutional Prostate Cancer Study of Genetic Susceptibility in Populations of African Descent,” Carcinogenesis, 2011, vol. 32 (9), pp. 1361-1365.
True L., et al., “A Molecular Correlate to the Gleason Grading System for Prostate Adenocarcinoma,” Proceedings of the National Academy of Sciences, 2006, vol. 103 (29), pp. 10991-10996.
Turashvili G., et al., “Novel Markers for Differentiation of Lobular and Ductal Invasive Breast Carcinomas by Laser Microdissection and Microarray Analysis,” BMC Cancer, 2007, vol. 7, pp. 55.
Vaarala M., “Differential Gene Expression in Prostate Cancer,” Biocenter Oulu, 2000.
Aaltomaa., et al., “Expression and Prognostic Value of CD44 Standard and Variant v3 and v6 Isoforms in Prostate Cancer,” Eur Urol., 2001, vol. 39, pp. 138-144.
Abrahams., et al., “Distinguishing Atrophy and High-Grade Prostatic Intraepithelial Neoplasia From Prostatic Adenocarcinoma With and Without Previous Adjuvant Hormone Therapy With the Aid of Cytokeratin 5/6,” Am J Clin Pathol, 2003, vol. 120, pp. 368-376.
Abrahams., et al., “Validation of Cytokeratin in 5/6 as an Effective Substitute for Keratin 903 in the Differentiation of Benign From Malignant Glands in Prostate Needle Biopsies,” Histopathology, 2002, vol. 41, pp. 35-41.
Aitchison A.A., et al., “Promoter Methylation Correlates with Reduced Smad4 Expression in Advanced Prostate Cancer,” Prostate, 2008, vol. 68 (6), pp. 661-674.
Anders M., et al., “Microarray Meta-analysis Defines Global Angiogenesis-related Gene Expression Signatures in Human Carcinomas,” Molecular Carcinogenesis, 2011.
Aoyagi., et al., “Specific Transcription Factors Prognostic for Prostate Cancer Progression,” Clin Cancer Res, 1998, vol. 4, pp. 2153-2160.
Barwick B.G., et al., “Prostate Cancer Genes Associated with TMPRSS2-ERG Gene Fusion and Prognostic of Biochemical Recurrence in Multiple Cohorts,” British Journal of Cancer, 2010, vol. 102 (3), pp. 570-576.
Bibikova., et al., “Expression Signatures That Correlated With Gleason Score and Relapse in Prostate Cancer,” Genomics, 2007, vol. 89 (6), pp. 666-672, available at www.sciencedirect.com.
Brewster., et al., “Preoperative p53, bcl-2, CD44 and E-cadherin Immunohistochemistry as Predictors of Biochemical Relapse After Radical Prostatectomy,” J Urol., 1999, vol. 161, pp. 1238-1243.
Chan E., et al., “Integrating Transcriptomics and Proteomics,” G & P Magazine, 2006, vol. 6 (3), pp. 20-26.
Chan., et al., “Insulin-Like Growth Factor-I (IGF-I) and IGF Binding Protein-3 as Predictors of Advanced-Stage Prostate Cancer,” Journal of Nat'l Cancer Institute, 2002, vol. 94, pp. 1-8.
Cheville J.C., et al., “Gene Panel Model Predictive of Outcome in Men at High-risk of Systemic Progression and Death from Prostate Cancer After Radical Retropubic Prostatectomy,” Journal of Clinical Oncology, 2008, vol. 26 (24), pp. 3930-3936.
Chiang et al., “Human Kallikrein-2 Gene Polymorphism is Associated with the Occurrence of Prostate Cancer”, Journal of Pathology, 2005, vol. 173(2), pp. 429-432.
Clarke R.A., et al., “Markers for Detection of Prostate Cancer,” Cancers, 2010, vol. 2 (2), pp. 1125-1154.
Creighton, “Multiple Oncogenic Pathway Signatures Show Coordinate Expression Patterns in Human Prostate Tumors,” PloS One, 2008, vol. 3 (3), 8 pages, online publication at milw.plosone.ora.
Davies et al., “Growth Factor Receptors and Oncogene Expression in Prostate Cells,” Am J Clin Oncol., 1988, vol. 11 (2), pp. S1-S7.
DeMarzo., et al., “CD44 and CD44v6 Downregulation in Clinical Prostatic Carcinoma: Relation to Gleason Grade and Cytoarchitecture,” Prostate, 1998, vol. 34, pp. 162-168.
Diamandis., et al., The New Human Kallikrein Gene Family: Implications in Carcinogenesis, TEM, 2000, vol. 11 (2), pp. 54-60.
Edwards., et al., “Gene Amplifications Associated With the Development of Hormone-Resistant Prostate Cancer,” Clin Cancer Res, 2003, vol. 9, pp. 5271-5281, downloaded from d:ncaner;es.aacr;o:rnas ug on Feb. 15, 2011.
Edwards., et al., “The Role of c-Jun and C-Fos Expression in Androgen-Independent Prostate Cancer,” J Pathol, 2004, vol. 2, pp. 153-158.
Ekici., et al., “Determination of Prognosis in Patients With Prostate Cancer Treated With Radical Prostatectomy: Prognostic Value of CD44v6 Score,” J Urol., 2002, vol. 167, pp. 2037-2041.
Eid., et al., “Expression of Early Growth Response Genes in Human Prostate Cancer,” Cancer Res, 1998, vol. 58, pp. 2461-2468, downloaded from d:ncancerres.aacriournas org on Feb. 10, 2011.
Extended European Search Report for EP Application No. 15152517.7, dated May 18, 2015, 7 pages.
Extended European Search Report for European Application No. 11813024.4, dated Dec. 2, 2013, 5 pages.
Gavrilov., et al., “Expression of Urokinase Plasminogen Activator and Receptor in Conjunction With the ets Family and AP-1 Complex Transcription Factors in High Grade Prostate Cancers,” Eur J Cancer, 2001, vol. 37, pp. 1033-1040.
Glinsky G.V., et al., “Gene Expression Profiling Predicts Clinical Outcome of Prostate Cancer,” Journal of Clinical Investigation, 2004, vol. 113 (6), pp. 913-923.
Goldstein, “Immunophenotypic Characterization of 225 Prostate Adenocarcinomas With Intermediate or High Gleason Scores,” Am J Clin Pathol, 2002, vol. 117, pp. 471-477.
Graff., et al., “Integrin-linked Kinase Expression Increases With Prostate Tumor Grade,” Clin Can Res, 2001, vol. 7, pp. 1987-1991.
Gunia., et al., “Expression of CD44s in Incidental Prostate Cancer is More Strongly Associated With Gleason Scores on Subsequent Radical Prostatectomies Than Conventional Prognostic Parameters,” Pathobiology, 2009, vol. 76, pp. 286-292.
Haese et al., “The Role of Human Glandular Kallikrein 2 for Prediction of Pathologically Organ Confined Prostate Cancer,” The Prostate, 2003, vol. 54(3), pp. 181-186.
Hale., et al., “Zinc a-2-Glycoprotein is Expressed by Malignant Prostatic Epithelium and May Serve as a Potential Serum Marker for Prostate Cancer,” Clin Can Res, 2001, vol. 7, pp. 846-853.
Horvath., et al., “Membranous Expression of Secreted Frizzled-Related Protein 4 Predicts for Good Prognosis in Localized Prostate Cancer and Inhibits PC3 Cellular Proliferation in Vitro,” Clin Can Res, 2004, vol. 10, pp. 615-625.
Horvath L.G., et al., “Loss of BMP2, Smad8 and Smad4 Expression in Prostate Cancer Progression,” Prostate, 2004, vol. 59 (3), pp. 234-242.
Hoshikawa Y., et al., “Hypoxia Induces Different Genes in the Lungs of Rats Compared with Mice,” Physiological Genomics, 2003, vol. 12 (3), pp. 209-219.
Humphrey, “Gleason Grading and Prognostic Factors in Carcinoma of the Prostate,” Modern Pathology, 2004, vol. 17, pp. 292-306.
International Search Report and Written Opinion for Application No. PCT/US2011/045253, dated Feb. 27, 2012, 13 pages.
Isler., et al., “Genomic Organization and Chromosomal Mapping of SPARC-like 1, a Gene Down Regulated in Cancers,” Int J Oncol., 2001, vol. 18, pp. 521-526.
Kallakury., et al., “Co-Downregulation of Cell Adhesion Proteins Alpha- and beta-catenins, p120CTN, E-cadherin, and CD44 in Prostatic Adenocarcinomas,” Hum Pathol, 2001, vol. 32, pp. 849-855.
Khuntia D., et al., “Recurrence-free Survival Rates After External-beam Radiotherapy for Patients with Clinical T1-T3 Prostate Carcinoma in the Prostate-specific Antigen Era: What Should We Expect?,” Cancer, 2004, vol. 100 (6), pp. 1283-1292.
Kim., et al., “The Retinoic Acid Synthesis Gene ALDH1 a2 Is a Candidate Tumor Suppressor in Prostate Cancer,” Cancer Res, 2005, vol. 65, pp. 8118-8124.
Kristiansen et al., “ALCAM/CD166 Is Up-Regulated in Low-Grade Prostate Cancer and Progressively Lost in High-Grade Lesions”, The Prostate, vol. 54, 2003, pp. 34-43.
Kristiansen G., et al., “Expression Profiling of Microdissected Matched Prostate Cancer Samples Reveals CD166/MEMD and CD24 as New Prognostic Markers for Patient Survival,” Journal of Pathology, 2005, vol. 205 (3), pp. 359-376.
Kube D.M., et al., “Optimization of Laser Capture Microdissection and RNA Amplification for Gene Expression Profiling of Prostate Cancer,” BMC Molecular Biology, 2007, vol. 8, pp. 25.
Lapointe J., et al., “Gene Expression Profiling Identifies Clinically Relevant Subtypes of Prostate Cancer,” Proceedings of the National Academy of Sciences, 2004, vol. 101 (3), pp. 811-816.
Latil A., et al., “Gene Expression Profiling in Clinically Localized Prostate Cancer: A Four-gene Expression Model Predicts Clinical Behavior,” Clinical Cancer Research, 2003, vol. 9 (15), pp. 5477-5485,downloaded from clincancer.aacrjournals.org on Feb. 23, 2011.
Latulippe., et al., “Comprehensive Gene Expression Analysis of Prostate Cancer Reveals Distinct Transcriptional Programs Associated With Metastatic Disease,” Cancer Res, 2002, vol. 62, pp. 4499-4506, downloaded from c:incacerres a3CriOUri:Z3j3 org on Feb. 24, 2011.
Lipponen., et al., “High Strome! Hyaluronan Level is Associated With Poor Differentiation and Metastasis in Prostate Cancer,” Eur J. Cancer, 2001, vol. 37, pp. 849-856.
Maki., et al., “Screening of Genetic and Expression Alterations of SRC1 Gene in Prostate Cancer,” Prostate, 2006, vol. 66, pp. 1391-1398.
Merz., et al., “Differential Expression of Transforming Growth Factor-Beta 1 and Beta 3 as Well as C-Fos mRNA in Normal Human Prostate, Benign Prostatic Hyperplasia and Prostatic Cancer,” World J. Urol., 1994, vol. 12, pp. 96-98.
Molinie., et al., “Diagnostic Utility of a p63/a-methyl-CoA-Racemase (p504s) Cocktail in Atypical Foci in the Prostate,” Modern Pathology, 2004, vol. 17, pp. 1180-1190.
Mukherjee., et al., “Raf-1 Expression May Influence Progression to Androgen Insensitive Prostate Cancer,” Prostate, 2005, vol. 64, pp. 101-107.
Noordzij., et al., “The Prognostic Value of CD44 Isoforms in Prostate Cancer Patients Treated by Radical Prostatectomy,” Clin Cancer Res, 1997, vol. 3, pp. 805-815, downloaded from c::ncaricerres aacqc;iJm:?j3 9 on Feb. 7, 2011.
Ohl F., et al., “Gene Expression Studies in Prostate Cancer Tissue: Which Reference Gene Should be Selected for Normalization?,” Journal of Molecular Medicine, 2005, vol. 83 (12), pp. 1014-1024.
Okada., et al., “Keratin Profiles in Normal/Hyperplastic Prostates and Prostate Carcinoma,” Virchows Arch A Pathol Anat Histopathol., 1992, vol. 421, pp. 157-161.
Paronetto., et al., “Expression of a Truncated Form of the c-Kit Tyrosine Kinase Receptor and Activation of Src Kinase in Human Prostatic Cancer,” American Journal of Pathology, 2004, vol. 164 (4), pp. 1243-1251.
Partin et al., “Use of Human Glandular Kallikrein 2 for the Detection of Prostate Cancer Preliminary Analysis,” Adult Urology, 1999, vol. 54(5), pp. 839-845.
Perner S., et al., “TMPRSS2-ETS Gene Fusion in Prostate Cancer,” Urologe A, 2007, vol. 46 (7), pp. 754-760.
Perttu M.C., et al., “Altered Levels of Smad2 and Smad4 are Associated with Human Prostate Carcinogenesis,” Prostate Cancer Prostatic Diseases, 2006, vol. 9 (2), pp. 185-189.
Ramaswamy., et al., “A Molecular Signature of Metastasis in Primary Solid Tumors,” Nature Genetics, 2003, vol. 33, pp. 49-54.
Rauhala., et al., “Clusterin is Epigenetically Regulated in Prostate Cancer,” Int. J. Cancer, 2008, vol. 123, pp. 1601-1609.
Schlomm., et al., “Molecular Cancer Phenotype in Normal Prostate Tissue,” Eur Urol., 2009, vol. 4, pp. 885-890.
Shariat., et al., “Survivin Expression is Associated With Features of Biologically Aggressive Prostate Carcinoma,” Cancer, 2004, vol. 100 (4), pp. 751-757.
Sheehan G.M., et al., “Smad4 Protein Expression Correlates with Grade, Stage and DNA Ploidy in Prostatic Adenocarcinomas,” Human Pathology, 2005, vol. 36 (11), pp. 1204-1209.
Singh D., et al., “Gene Expression Correlates of Clinical Prostate Cancer Behavior,” Cancer Cell, 2002, vol. 1 (2), pp. 203-209.
Sorlie T., et al., “Gene Expression Patterns of Breast Carcinomas Distinguish Tumor Subclasses with Clinical Implications,” Proceedings of the National Academy of Sciences, 2001, vol. 98 (19), pp. 10869-10874.
Stattin., et al., “High Levels of Circulating Insulin-Like Growth Factor-I Increase Prostate Cancer Risk: A Prospective Study in a Population-Based Nonscreened Cohort,” Journal of Clinical Oncology, 2004, vol. 22 (15), pp. 3104-3112.
Stephenson A.J., et al., “Integration of Gene Expression Profiling and Clinical Variables to Predict Prostate Carcinoma Recurrence after Radical Prostatectomy,” Molecular Prediction of Prostate Ca Recurrence, 2005, vol. 104 (2), pp. 290-298.
Tang S.C., et al., “Expression of Glutathione S-transferase M2 in Stage I/II Non-small Cell Lung Cancer and Alleviation of DNA Damage Exposure to Benzo[a]pyrene,” Toxicology Letters, 2010, vol. 192 (3), pp. 316-323.
Taylor., et al., “Integrative Genomic Profiling of Human Prostate Cancer,” Cancer Cell, 2010, vol. 18, pp. 1-12.
Thalmann., et al., “Osteopontin: Possible Role in Prostate Cancer Progression,” Clin Cancer Res, 1999, vol. 5, pp. 2271-2277, downloaded from d:no:arx:erret,..r3acOurnais org on Feb. 7, 2011.
Thomas R., et al., “Differential Expression of Osteonectin/SPARC During Human Prostate Cancer Progression,” Clinical Cancer Research, 2000, vol. 6 (3), pp. 1140-1149, downloaded from clincancer.aacrjournals.org on Feb. 7, 2011.
Van Leenders., et al., “Expression of Basal Cell Keratins in Human Prostate Cancer Metastases and Cell Lines,” J. Pathol., 2001, vol. 195, pp. 563-570.
Van Leenders., et al., “Intermediate Cells in Human Prostate Epithelium Are Enriched in Proliferative Inflammatory Atrophy,” American Journal of Pathology, 2003, vol. 162 ( 5), pp. 1529-1537.
Vis., et al., “Prognostic Value of Cell Cycle Proteins p27(kiplS) and MIB-1, and the Cell Adhesion Protein CD44s in Surgically Treated Patients With Prostate Cancer,” J Urol., 2000, vol. 164, pp. 2156-2161.
Written Opinion dated Nov. 17, 2014, for Singapore Patent Application No. 201300086-4.
Xu., et al., “Expressions of MAD2 and p55CDC in Prostate Cancer and Their Correlations With the Prostate Cancer Grading,” Journal of Peking University (Health Sciences), 2003, vol. 35 (6), pp. 586-590.
Yan., et al., “Steroid Receptor Coactivator-3/AIB1 Promotes Cell Migration and Invasiveness Through Focal Adhesion Turnover and Matrix Metalloproteinase Expression,” Cancer Res, 2008, vol. 68, pp. 5460-5468, downloaded from c;:ricanc;:m3.aacijouma::.org on Feb. 15, 2011.
Yang., et al., “Differential Expression of Cytokeratin mRNA and Protein in Normal Prostate, Prostatic Intraepithelial Neoplasia, and Invasive Carcinoma,” American Journal of Pathology, 1997, vol. 150 (2), pp. 693-704.
Yang., et al., “Meta-Analysis of Several Gene Lists for Distinct Types of Cancer: A Simple Way to Reveal Common Prognostic Markers,” BMC Bioinformatics, 2007, vol. 8, pp. 1-17.
Zeng., et al., “Apoptosis Incidence and Protein Expression of p53, TGF-Beta Receptor II, p27Kip1, and Smad4 in Benign, Premalignant, and Malignant Human Prostate,” Hum Pathol., 2004, vol. 35, pp. 290-297.
Zhou., et al., “SRC-3 Is Required for Prostate Cancer Cell Proliferation and Survival,” Cancer Res, 2005, vol. 65, pp. 7976-7983, downloaded from c,i,...aancerres aacnourriais.oi-g on Feb. 15, 2011.
Li et al., Prostatic Intraepithelial Neoplasia and Adenocarcinoma in Mice Expressing a Probasin-Neu Oncogenic Transgene, Carcinogenesis, vol. 27, No. 5, 2006, pp. 1054-1067.
Murphy et al., “Patented Prostate Cancer Biomarkers”, Nature Reviews Urology, vol. 9, No. 8, 2012, pp. 464-472.
Partial European Search Report dated May 11, 2017, for European Patent Application No. 16191856.0.
Cuzick et al,. “Prognostc value of an RNA expression signature derived from cell cycle proliferation genes in patient with prostate cancer: a retrospective study”, Lancet Oncology, vol. 12, 2011. pp. 245-255.
Kidokoro et al., “CDC20, a potential cancer therapeutic target, is negatively regulated by p53”, Oncogene, vol. 27. 2008, pp. 1562-1571.
Haller et al., “Equivalence Test in Quantitative Reverse Transcription Polymerase Chain Reaction: Confirmation of Reference Genes Suitable for Normalization”, Analytical Biochemistry, vol. 335, No. 1, 2004, pp. 1-9.
Yang et al., “A Molecular Classification of Papillary Renal Cell Carcinoma”, Cancer Research, vol. 65, 2005, pp. 5628-5637.
Yao et al., “A Three-Gene Expression Signature Model to Predict Clinical Outcome of Clear Cell Renal Carcinoma”, Int. J. Cancer, vol. 123, No. 5, 2008, pp. 1126-1132.
Partial European Search Report dated May 8, 2017, for European Patent Application No. 17153152.8.
Extended Search Report dated Aug. 16, 2017, for European Patent Application No. 16191856.0.
Ohl et al., Gene expression studies in prostate cancer tissue: which reference gene should be selected for normalization?, J. Mol. Med. (Berl) 83(12):1014-24, Abstract, 2005.
Related Publications (1)
Number Date Country
20160097105 A1 Apr 2016 US
Provisional Applications (3)
Number Date Country
61368217 Jul 2010 US
61414310 Nov 2010 US
61485536 May 2011 US
Continuations (1)
Number Date Country
Parent 13190391 Jul 2011 US
Child 14887605 US