US20120028264A1

US20120028264A1 - Method for using gene expression to determine prognosis of prostate cancer

Info

Publication number: US20120028264A1
Application number: US13/190,391
Authority: US
Inventors: Steven Shak; Frederick L. Baehner; Tara Maddala; Mark Lee; Robert J. Pelham; Wayne Cowens; Diana Cherbavaz; Michael C. Kiefer; Michael Crager; Audrey Goddard; Joffre B. Baker
Original assignee: Individual
Current assignee: Mdxhealth SA
Priority date: 2010-07-27
Filing date: 2011-07-25
Publication date: 2012-02-02
Also published as: CA2804626A1; EP3147373A1; JP2013532482A; IL243205A; JP6246845B2; DK3147373T3; US20200255911A1; CA3081061A1; IL251403A0; EP3556870A1; JP7042784B2; EP3147373B1; JP2020031642A; US10260104B2; EP3556870B9; ES2537403T3; EP2913405B1; EP2598659A2; EP4083233A2; HK1212395A1

Abstract

Molecular assays that involve measurement of expression levels of prognostic biomarkers, or co-expressed biomarkers, from a biological sample obtained from a prostate cancer patient, and analysis of the measured expression levels to provide information concerning the likely prognosis for said patient, and likelihood that said patient will have a recurrence of prostate cancer, or to classify the tumor by likelihood of clinical outcome or TMPRSS2 fusion status, are provided herein.

Description

This application 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.

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 N0M0G2-4) or (T1b, c, T1, T2, N0 M0 Any G); Stage III: T3 N0 M0 Any G; Stage 1V: (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 Andrés 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 (“C_T”). Fluorescence values are recorded during every cycle and represent the amount of product amplified to that point in the amplification reaction. The threshold cycle (C_T) is generally described as the point when the fluorescent signal is first recorded as statistically significant. Alternatively, data may be expressed as a crossing point (“Cp”). The Cp value is calculated by determining the second derivatives of entire qPCR amplification curves and their maximum value. The Cp value represents the cycle at which the increase of fluorescence is highest and where the logarithmic phase of a PCR begins.
To minimize errors and the effect of sample-to-sample variation, RT-PCR is usually performed using an internal standard. The ideal internal standard gene (also referred to as a reference gene) is expressed at a quite constant level among cancerous and non-cancerous tissue of the same origin (i.e., a level that is not significantly different among normal and cancerous tissues), and is not significantly affected by the experimental treatment (i.e., does not exhibit a significant difference in expression level in the relevant tissue as a result of exposure to chemotherapy), and expressed at a quite constant level among the same tissue taken from different patients. For example, reference genes useful in the methods disclosed herein should not exhibit significantly different expression levels in cancerous prostate as compared to normal prostate tissue. RNAs frequently used to normalize patterns of gene expression are mRNAs for the housekeeping genes glyceraldehyde-3-phosphate-dehydrogenase (GAPDH) and (3-actin. Exemplary reference genes used for normalization comprise one or more of the following genes: AAMP, ARF1, ATP5E, CLTC, GPS1, and PGK1. Gene expression measurements can be normalized relative to the mean of one or more (e.g., 2, 3, 4, 5, or more) reference genes. Reference-normalized expression measurements can range from 2 to 15, where a one unit increase generally reflects a 2-fold increase in RNA quantity.
Real time PCR is compatible both with quantitative competitive PCR, where internal competitor for each target sequence is used for normalization, and with quantitative comparative PCR using a normalization gene contained within the sample, or a housekeeping gene for RT-PCR. For further details see, e.g. Held et al., Genome Research 6:986-994 (1996).
The steps of a representative protocol for use in the methods of the present disclosure use fixed, paraffin-embedded tissues as the RNA source. For example, mRNA isolation, purification, primer extension and amplification can be performed according to methods available in the art. (see, e.g., Godfrey et al. J. Molec. Diagnostics 2: 84-91 (2000); Specht et al., Am. J. Pathol. 158: 419-29 (2001)). Briefly, a representative process starts with cutting about 10 μm thick sections of paraffin-embedded tumor tissue samples. The RNA is then extracted, and protein and DNA depleted from the RNA-containing sample. After analysis of the RNA concentration, RNA is reverse transcribed using gene specific primers followed by RT-PCR to provide for cDNA amplification products.
Design of Intron-Based PCR Primers and Probes
PCR primers and probes can be designed based upon exon or intron sequences present in the mRNA transcript of the gene of interest. Primer/probe design can be performed using publicly available software, such as the DNA BLAT software developed by Kent, W. J., Genome Res. 12(4):656-64 (2002), or by the BLAST software including its variations.
Where necessary or desired, repetitive sequences of the target sequence can be masked to mitigate non-specific signals. Exemplary tools to accomplish this include the Repeat Masker program available on-line through the Baylor College of Medicine, which screens DNA sequences against a library of repetitive elements and returns a query sequence in which the repetitive elements are masked. The masked intron sequences can then be used to design primer and probe sequences using any commercially or otherwise publicly available primer/probe design packages, such as Primer Express (Applied Biosystems); MGB assay-by-design (Applied Biosystems); Primer3 (Steve Rozen and Helen J. Skaletsky (2000) Primer3 on the WWW for general users and for biologist programmers. See S. Rrawetz, S. Misener, Bioinformatics Methods and Protocols: Methods in Molecular Biology, pp. 365-386 (Humana Press).
Other factors that can influence PCR primer design include primer length, melting temperature (Tm), and G/C content, specificity, complementary primer sequences, and 3′-end sequence. In general, optimal PCR primers are generally 17-30 bases in length, and contain about 20-80%, such as, for example, about 50-60% G+C bases, and exhibit Tm's between 50 and 80° C., e.g. about 50 to 70° C.
For further guidelines for PCR primer and probe design see, e.g. Dieffenbach, CW. et al, “General Concepts for PCR Primer Design” in: PCR Primer, A Laboratory Manual, Cold Spring Harbor Laboratory Press,. New York, 1995, pp. 133-155; Innis and Gelfand, “Optimization of PCRs” in: PCR Protocols, A Guide to Methods and Applications, CRC Press, London, 1994, pp. 5-11; and Plasterer, T. N. Primerselect: Primer and probe design. Methods Mol. Biol. 70:520-527 (1997), the entire disclosures of which are hereby expressly incorporated by reference.
Table A provides further information concerning the primer, probe, and amplicon sequences associated with the Examples disclosed herein.
MassARRAY® System
In MassARRAY-based methods, such as the exemplary method developed by Sequenom, Inc. (San Diego, Calif.) following the isolation of RNA and reverse transcription, the obtained cDNA is spiked with a synthetic DNA molecule (competitor), which matches the targeted cDNA region in all positions, except a single base, and serves as an internal standard. The cDNA/competitor mixture is PCR amplified and is subjected to a post-PCR shrimp alkaline phosphatase (SAP) enzyme treatment, which results in the dephosphorylation of the remaining nucleotides. After inactivarion of the alkaline phosphatase, the PCR products from the competitor and cDNA are subjected to primer extension, which generates distinct mass signals for the competitor- and cDNA-derives PCR products. After purification, these products are dispensed on a chip array, which is pre-loaded with components needed for analysis with matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis. The cDNA present in the reaction is then quantified by analyzing the ratios of the peak areas in the mass spectrum generated. For further details see, e.g. Ding and Cantor, Proc. Natl. Acad. Sci. USA 100:3059-3064 (2003).
Other PCR-Based Methods
Further PCR-based techniques that can find use in the methods disclosed herein include, for example, BeadArray® technology (Illumina, San Diego, Calif.; Oliphant et al., Discovery of Markers for Disease (Supplement to Biotechniques), June 2002; Ferguson et al., Analytical Chemistry 72:5618 (2000)); BeadsArray for Detection of Gene Expression® (BADGE), using the commercially available LuminexlOO LabMAP® system and multiple color-coded microspheres (Luminex Corp., Austin, Tex.) in a rapid assay for gene expression (Yang et al., Genome Res. 11:1888-1898 (2001)); and high coverage expression profiling (HiCEP) analysis (Fukumura et al., Nucl. Acids. Res. 31(16) e94 (2003).
Microarrays
Expression levels of a gene or microArray of interest can also be assessed using the microarray technique. In this method, polynucleotide sequences of interest (including cDNAs and oligonucleotides) are arrayed on a substrate. The arrayed sequences are then contacted under conditions suitable for specific hybridization with detectably labeled cDNA generated from RNA of a test sample. As in the RT-PCR method, the source of RNA typically is total RNA isolated from a tumor sample, and optionally from normal tissue of the same patient as an internal control or cell lines. RNA can be extracted, for example, from frozen or archived paraffin-embedded and fixed (e.g. formalin-fixed) tissue samples.
For example, PCR amplified inserts of cDNA clones of a gene to be assayed are applied to a substrate in a dense array. Usually at least 10,000 nucleotide sequences are applied to the substrate. For example, the microarrayed genes, immobilized on the microchip at 10,000 elements each, are suitable for hybridization under stringent conditions. Fluorescently labeled cDNA probes may be generated through incorporation of fluorescent nucleotides by reverse transcription of RNA extracted from tissues of interest. Labeled cDNA probes applied to the chip hybridize with specificity to each spot of DNA on the array. After washing under stringent conditions to remove non-specifically bound probes, the chip is scanned by confocal laser microscopy or by another detection method, such as a CCD camera. Quantitation of hybridization of each arrayed element allows for assessment of corresponding RNA abundance.
With dual color fluorescence, separately labeled cDNA probes generated from two sources of RNA are hybridized pair wise to the array. The relative abundance of the transcripts from the two sources corresponding to each specified gene is thus determined simultaneously. The miniaturized scale of the hybridization affords a convenient and rapid evaluation of the expression pattern for large numbers of genes. Such methods have been shown to have the sensitivity required to detect rare transcripts, which are expressed at a few copies per cell, and to reproducibly detect at least approximately two-fold differences in the expression levels (Schena et at, Proc. Natl. Acad. ScL USA 93(2):106-149 (1996)). Microarray analysis can be performed by commercially available equipment, following manufacturer's protocols, such as by using the Affymetrix GenChip® technology, or Incyte's microarray technology.
Serial Analysis of Gene Expression (SAGE)
Serial analysis of gene expression (SAGE) is a method that allows the simultaneous and quantitative analysis of a large number of gene transcripts, without the need of providing an individual hybridization probe for each transcript. First, a short sequence tag (about 10-14 bp) is generated that contains sufficient information to uniquely identify a transcript, provided that the tag is obtained from a unique position within each transcript. Then, many transcripts are linked together to form long serial molecules, that can be sequenced, revealing the identity of the multiple tags simultaneously. The expression pattern of any population of transcripts can be quantitatively evaluated by determining the abundance of individual tags, and identifying the gene corresponding to each tag. For more details see, e.g. Velculescu et al., Science 270:484-487 (1995); and Velculescu et al., Cell 88:243-51 (1997).
Gene Expression Analysis by Nucleic Acid Sequencing
Nucleic acid sequencing technologies are suitable methods for analysis of gene expression. The principle underlying these methods is that the number of times a cDNA sequence is detected in a sample is directly related to the relative expression of the RNA corresponding to that sequence. These methods are sometimes referred to by the term Digital Gene Expression (DGE) to reflect the discrete numeric property of the resulting data. Early methods applying this principle were Serial Analysis of Gene Expression (SAGE) and Massively Parallel Signature Sequencing (MPSS). See, e.g., S. Brenner, et al., Nature Biotechnology 18(6):630-634 (2000). More recently, the advent of “next-generation” sequencing technologies has made DGE simpler, higher throughput, and more affordable. As a result, more laboratories are able to utilize DGE to screen the expression of more genes in more individual patient samples than previously possible. See, e.g., J. Marioni, Genome Research 18(9):1509-1517 (2008); R. Morin, Genome Research 18(4):610-621 (2008); A. Mortazavi, Nature Methods 5(7):621-628 (2008); N. Cloonan, Nature Methods 5(7):613-619 (2008).
Isolating RNA from Body Fluids
Methods of isolating RNA for expression analysis from blood, plasma and serum (see, e.g., K. Enders, et al., Clin Chem 48, 1647-53 (2002) (and references cited therein) and from urine (see, e.g., R. Boom, et al., J Clin Microbiol. 28, 495-503 (1990) and references cited therein) have been described.
Immunohistochemistry
Immunohistochemistry methods are also suitable for detecting the expression levels of genes and applied to the method disclosed herein. Antibodies (e.g., monoclonal antibodies) that specifically bind a gene product of a gene of interest can be used in such methods. The antibodies can be detected by direct labeling of the antibodies themselves, for example, with radioactive labels, fluorescent labels, hapten’ labels such as, biotin, or an enzyme such as horse radish peroxidase or alkaline phosphatase. Alternatively, unlabeled primary antibody can be used in conjunction with a labeled secondary antibody specific for the primary antibody. Immunohistochemistry protocols and kits are well known in the art and are commercially available.
Proteomics
The term “proteome” is defined as the totality of the proteins present in a sample (e.g. tissue, organism, or cell culture) at a certain point of time. Proteomics includes, among other things, study of the global changes of protein expression in a sample (also referred to as “expression proteomics”). Proteomics typically includes the following steps: (1) separation of individual proteins in a sample by 2-D gel electrophoresis (2-D PAGE); (2) identification of the individual proteins recovered from the gel, e.g. my mass spectrometry or N-terminal sequencing, and (3) analysis of the data using bioinformatics.
General Description of the mRNA/microRNA Isolation, Purification and Amplification
The steps of a representative protocol for profiling gene expression using fixed, paraffin-embedded tissues as the RNA source, including mRNA or microRNA isolation, purification, primer extension and amplification are provided in various published journal articles. (See, e.g., T. E. Godfrey, et al., J. Molec. Diagnostics 2: 84-91 (2000); K. Specht et al., Am. J. Pathol. 158: 419-29 (2001), M. Cronin, et al., Am J Pathol 164:35-42 (2004)). Briefly, a representative process starts with cutting a tissue sample section (e.g. about 10 μm thick sections of a paraffin-embedded tumor tissue sample). The RNA is then extracted, and protein and DNA are removed. After analysis of the RNA concentration, RNA repair is performed if desired. The sample can then be subjected to analysis, e.g., by reverse transcribed using gene specific promoters followed by RT-PCR.
Statistical Analysis of Expression Levels in Identification of Genes and microRNAs
One skilled in the art will recognize that there are many statistical methods that may be used to determine whether there is a significant relationship between a parameter of interest (e.g., recurrence) and expression levels of a marker gene/microRNA as described here. In an exemplary embodiment, the present invention provides a stratified cohort sampling design (a form of case-control sampling) using tissue and data from prostate cancer patients. Selection of specimens was stratified by T stage (T1, T2), year cohort (<1993, ≧1993), and prostatectomy Gleason Score (low/intermediate, high). All patients with clinical recurrence were selected and a sample of patients who did not experience a clinical recurrence was selected. For each patient, up to two enriched tumor specimens and one normal-appearing tissue sample was assayed.
All hypothesis tests were reported using two-sided p-values. To investigate if there is a significant relationship of outcomes (clinical recurrence-free interval (cRFI), biochemical recurrence-free interval (bRFI), prostate cancer-specific survival (PCSS), and overall survival (OS)) with individual genes and/or microRNAs, demographic or clinical covariates Cox Proportional Hazards (PH) models using maximum weighted pseudo partial-likelihood estimators were used and p-values from Wald tests of the null hypothesis that the hazard ratio (HR) is one are reported. To investigate if there is a significant relationship between individual genes and/or microRNAs and Gleason pattern of a particular sample, ordinal logistic regression models using maximum weighted likelihood methods were used and p-values from Wald tests of the null hypothesis that the odds ratio (OR) is one are reported.

Coexpression Analysis

The present disclosure provides a method to determine tumor stage based on the expression of staging genes, or genes that co-express with particular staging genes. To perform particular biological processes, genes often work together in a concerted way, i.e. they are co-expressed. Co-expressed gene groups identified for a disease process like cancer can serve as biomarkers for tumor status and disease progression. Such co-expressed genes can be assayed in lieu of, or in addition to, assaying of the staging gene with which they are co-expressed.
In an exemplary embodiment, the joint correlation of gene expression levels among prostate cancer specimens under study may be assessed. For this purpose, the correlation structures among genes and specimens may be examined through hierarchical cluster methods. This information may be used to confirm that genes that are known to be highly correlated in prostate cancer specimens cluster together as expected. Only genes exhibiting a nominally significant (unadjusted p<0.05) relationship with cRFI in the univariate Cox PH regression analysis will be included in these analyses.
One skilled in the art will recognize that many co-expression analysis methods now known or later developed will fall within the scope and spirit of the present invention. These methods may incorporate, for example, correlation coefficients, co-expression network analysis, clique analysis, etc., and may be based on expression data from RT-PCR, microarrays, sequencing, and other similar technologies. For example, gene expression clusters can be identified using pair-wise analysis of correlation based on Pearson or Spearman correlation coefficients. (See, e.g., Pearson K. and Lee A., Biometrika 2, 357 (1902); C. Spearman, Amer. J. Psychol 15:72-101 (1904); J. Myers, A. Well, Research Design and Statistical Analysis, p. 508 (2nd Ed., 2003).)

Normalization of Expression Levels

The expression data used in the methods disclosed herein can be normalized. Normalization refers to a process to correct for (normalize away), for example, differences in the amount of RNA assayed and variability in the quality of the RNA used, to remove unwanted sources of systematic variation in Ct or Cp measurements, and the like. With respect to RT-PCR experiments involving archived fixed paraffin embedded tissue samples, sources of systematic variation are known to include the degree of RNA degradation relative to the age of the patient sample and the type of fixative used to store the sample. Other sources of systematic variation are attributable to laboratory processing conditions.
Assays can provide for normalization by incorporating the expression of certain normalizing genes, which do not significantly differ in expression levels under the relevant conditions. Exemplary normalization genes disclosed herein include housekeeping genes. (See, e.g., E. Eisenberg, et al., Trends in Genetics 19(7):362-365 (2003).) Normalization can be based on the mean or median signal (Ct or Cp) of all of the assayed genes or a large subset thereof (global normalization approach). In general, the normalizing genes, also referred to as reference genes should be genes that are known not to exhibit significantly different expression in prostate cancer as compared to non-cancerous prostate tissue, and are not significantly affected by various sample and process conditions, thus provide for normalizing away extraneous effects.
In exemplary embodiments, one or more of the following genes are used as references by which the mRNA or microRNA expression data is normalized: AAMP, ARF1, ATP5E, CLTC, GPS1, and PGK1. In another exemplary embodiment, one or more of the following microRNAs are used as references by which the expression data of microRNAs are normalized: hsa-miR-106a; hsa-miR-146b-5p; hsa-miR-191; hsa-miR-19b; and hsa-miR-92a. The calibrated weighted average C_Tor Cp measurements for each of the prognostic and predictive genes or microRNAs may be normalized relative to the mean of five or more reference genes or microRNAs.
Those skilled in the art will recognize that normalization may be achieved in numerous ways, and the techniques described above are intended only to be exemplary, not exhaustive.

Standardization of Expression Levels

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

Kits of the Invention

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

Reports

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

Computer Program

The values from the assays described above, such as expression data, can be calculated and stored manually. Alternatively, the above-described steps can be completely or partially performed by a computer program product. The present invention thus provides a computer program product including a computer readable storage medium having a computer program stored on it. The program can, when read by a computer, execute relevant calculations based on values obtained from analysis of one or more biological sample from an individual (e.g., gene expression levels, normalization, standardization, thresholding, and conversion of values from assays to a score and/or text or graphical depiction of tumor stage and related information). The computer program product has stored therein a computer program for performing the calculation.
The present disclosure provides systems for executing the program described above, which system generally includes: a) a central computing environment; b) an input device, operatively connected to the computing environment, to receive patient data, wherein the patient data can include, for example, expression level or other value obtained from an assay using a biological sample from the patient, or microarray data, as described in detail above; c) an output device, connected to the computing environment, to provide information to a user (e.g., medical personnel); and d) an algorithm executed by the central computing environment (e.g., a processor), where the algorithm is executed based on the data received by the input device, and wherein the algorithm calculates an expression score, thresholding, or other functions described herein. The methods provided by the present invention may also be automated in whole or in part.
All aspects of the present invention may also be practiced such that a limited number of additional genes and/or microRNAs that are co-expressed or functionally related with the disclosed genes, for example as evidenced by statistically meaningful Pearson and/or Spearman correlation coefficients, are included in a test in addition to and/or in place of disclosed genes.
Having described the invention, the same will be more readily understood through reference to the following Examples, which are provided by way of illustration, and are not intended to limit the invention in any way.

EXAMPLES

Example 1

RNA Yield and Gene Expression Profiles in Prostate Cancer Biopsy Cores

Clinical tools based on prostate needle core biopsies are needed to guide treatment planning at diagnosis for men with localized prostate cancer. Limiting tissue in needle core biopsy specimens poses significant challenges to the development of molecular diagnostic tests. This study examined RNA extraction yields and gene expression profiles using an RT-PCR assay to characterize RNA from manually micro-dissected fixed paraffin embedded (FPE) prostate cancer needle biopsy cores. It also investigated the association of RNA yields and gene expression profiles with Gleason score in these specimens.
Patients and Samples
This study determined the feasibility of gene expression profile analysis in prostate cancer needle core biopsies by evaluating the quantity and quality of RNA extracted from fixed paraffin-embedded (FPE) prostate cancer needle core biopsy specimens. Forty-eight (48) formalin-fixed blocks from prostate needle core biopsy specimens were used for this study. Classification of specimens was based on interpretation of the Gleason score (2005 Int'l Society of Urological Pathology Consensus Conference) and percentage tumor (<33%, 33-66%, >66%) involvement as assessed by pathologists.

TABLE 1

Distribution of cases

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

Low (≦6)	5	5	6
Intermediate (7)	5	5	6
High (8, 9, 10)	5	5	6
Total	15	15	18

Assay Methods
Fourteen (14) serial 5 μm unstained sections from each FPE tissue block were included in the study. The first and last sections for each case were H&E stained and histologically reviewed to confirm the presence of tumor and for tumor enrichment by manual micro-dissection.
RNA from enriched tumor samples was extracted using a manual RNA extraction process. RNA was quantitated using the RiboGreen® assay and tested for the presence of genomic DNA contamination. Samples with sufficient RNA yield and free of genomic DNA tested for gene expression levels of a 24-gene panel of reference and cancer-related genes using quantitative RT-PCR. The expression was normalized to the average of 6 reference genes (AAMP, ARF1, ATP5E, CLTC, EEF1A1, and GPX1).
Statistical Methods
Descriptive statistics and graphical displays were used to summarize standard pathology metrics and gene expression, with stratification for Gleason Score category and percentage tumor involvement category. Ordinal logistic regression was used to evaluate the relationship between gene expression and Gleason Score category.
Results
The RNA yield per unit surface area ranged from 16 to 2406 ng/mm2. Higher RNA yield was observed in samples with higher percent tumor involvement (p=0.02) and higher Gleason score (p=0.01). RNA yield was sufficient (>200 ng) in 71% of cases to permit 96-well RT-PCR, with 87% of cases having >100 ng RNA yield. The study confirmed that gene expression from prostate biopsies, as measured by qRT-PCR, was comparable to FPET samples used in commercial molecular assays for breast cancer. In addition, it was observed that greater biopsy RNA yields are found with higher Gleason score and higher percent tumor involvement. Nine genes were identified as significantly associated with Gleason score (p<0.05) and there was a large dynamic range observed for many test genes.

Example 2

Gene Expression Analysis for Genes Associated with Prognosis in Prostate Cancer

Patients and Samples
Approximately 2600 patients with clinical stage T1/T2 prostate cancer treated with radical prostatectomy (RP) at the Cleveland Clinic between 1987 and 2004 were identified. Patients were excluded from the study design if they received neo-adjuvant and/or adjuvant therapy, if pre-surgical PSA levels were missing, or if no tumor block was available from initial diagnosis. 127 patients with clinical recurrence and 374 patients without clinical recurrence after radical prostatectomy were randomly selected using a cohort sampling design. The specimens were stratified by T stage (T1, T2), year cohort (<1993, ≧1993), and prostatectomy Gleason score (low/intermediate, high). Of the 501 sampled patients, 51 were excluded for insufficient tumor; 7 were excluded due to clinical ineligibility; 2 were excluded due to poor quality of gene expression data; and 10 were excluded because primary Gleason pattern was unavailable. Thus, this gene expression study included tissue and data from 111 patients with clinical recurrence and 330 patients without clinical recurrence after radical prostatectomies performed between 1987 and 2004 for treatment of early stage (T1, T2) prostate cancer.
Two fixed paraffin embedded (FPE) tissue specimens were obtained from prostate tumor specimens in each patient. The sampling method (sampling method A or B) depended on whether the highest Gleason pattern is also the primary Gleason pattern. For each specimen selected, the invasive cancer cells were at least 5.0 mm in dimension, except in the instances of pattern 5, where 2.2 mm was accepted. Specimens were spatially distinct where possible.

TABLE 2

Sampling Methods

Sampling Method A	Sampling Method B

For patients whose prostatectomy	For patients whose prostatectomy
primary Gleason pattern is also	primary Gleason pattern is not
the highest Gleason pattern	the highest Gleason pattern
Specimen 1 (A1) = primary	Specimen 1 (B1) = highest
Gleason pattern	Gleason pattern
Select and mark largest focus	Select highest Gleason pattern tissue
(greatest cross-sectional area) of	from spatially distinct area from
primary Gleason pattern tissue.	specimen B2, if possible. Invasive
Invasive cancer area ≧5.0 mm.	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	Specimen 2 (B2) = primary
Gleason pattern	Gleason pattern
Select and mark secondary Gleason	Select largest focus (greatest
pattern tissue from spatially	cross-sectional area) of primary
distinct area from specimen A1.	Gleason pattern tissue. Invasive
Invasive cancer area ≧5.0 mm.	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

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

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		Highest
	Pattern		Pattern

	Official Symbol	OR	p-value	OR	p-value

ABCA5	0.78	0.041
ABCG2	0.65	0.001	0.72	0.012
ACOX2	0.44	<.001	0.53	<.001
ADH5	0.45	<.001	0.42	<.001
AFAP1			0.79	0.038
AIG1			0.77	0.024
AKAP1	0.63	0.002
AKR1C1	0.66	0.003	0.63	<.001
AKT3	0.68	0.006	0.77	0.010
ALDH1A2	0.28	<.001	0.33	<.001
ALKBH3	0.77	0.040	0.77	0.029
AMPD3	0.67	0.007
ANPEP	0.68	0.008	0.59	<.001
ANXA2	0.72	0.018
APC			0.69	0.002
AXIN2	0.46	<.001	0.54	<.001
AZGP1	0.52	<.001	0.53	<.001
BIK	0.69	0.006	0.73	0.003
BIN1	0.43	<.001	0.61	<.001
BTG3			0.79	0.030
BTRC	0.48	<.001	0.62	<.001
C7	0.37	<.001	0.55	<.001
CADM1	0.56	<.001	0.69	0.001
CAV1	0.58	0.002	0.70	0.009
CAV2	0.65	0.029
CCNH	0.67	0.006	0.77	0.048
CD164	0.59	0.003	0.57	<.001
CDC25B	0.77	0.035
CDH1			0.66	<.001
CDK2			0.71	0.003
CDKN1C	0.58	<.001	0.57	<.001
CDS2			0.69	0.002
CHN1	0.66	0.002
COL6A1	0.44	<.001	0.66	<.001
COL6A3	0.66	0.006
CSRP1	0.42	0.006
CTGF	0.74	0.043
CTNNA1	0.70	<.001	0.83	0.018
CTNNB1	0.70	0.019
CTNND1			0.75	0.028
CUL1			0.74	0.011
CXCL12	0.54	<.001	0.74	0.006
CYP3A5	0.52	<.001	0.66	0.003
CYR61	0.64	0.004	0.68	0.005
DDR2	0.57	0.002	0.73	0.004
DES	0.34	<.001	0.58	<.001
DLGAP1	0.54	<.001	0.62	<.001
DNM3	0.67	0.004
DPP4	0.41	<.001	0.53	<.001
DPT	0.28	<.001	0.48	<.001
DUSP1	0.59	<.001	0.63	<.001
EDNRA	0.64	0.004	0.74	0.008
EGF			0.71	0.012
EGR1	0.59	<.001	0.67	0.009
EGR3	0.72	0.026	0.71	0.025
EIF5			0.76	0.025
ELK4	0.58	0.001	0.70	0.008
ENPP2	0.66	0.002	0.70	0.005
EPHA3	0.65	0.006
EPHB2	0.60	<.001	0.78	0.023
EPHB4	0.75	0.046	0.73	0.006
ERBB3	0.76	0.040	0.75	0.013
ERBB4			0.74	0.023
ERCC1	0.63	<.001	0.77	0.016
FAAH	0.67	0.003	0.71	0.010
FAM107A	0.35	<.001	0.59	<.001
FAM13C	0.37	<.001	0.48	<.001
FAS	0.73	0.019	0.72	0.008
FGF10	0.53	<.001	0.58	<.001
FGF7	0.52	<.001	0.59	<.001
FGFR2	0.60	<.001	0.59	<.001
FKBP5	0.70	0.039	0.68	0.003
FLNA	0.39	<.001	0.56	<.001
FLNC	0.33	<.001	0.52	<.001
FOS	0.58	<.001	0.66	0.005
FOXO1	0.57	<.001	0.67	<.001
FOXQ1			0.74	0.023
GADD45B	0.62	0.002	0.71	0.010
GHR	0.62	0.002	0.72	0.009
GNRH1	0.74	0.049	0.75	0.026
GPM6B	0.48	<.001	0.68	<.001
GPS1			0.68	0.003
GSN	0.46	<.001	0.77	0.027
GSTM1	0.44	<.001	0.62	<.001
GSTM2	0.29	<.001	0.49	<.001
HGD			0.77	0.020
HIRIP3	0.75	0.034
HK1	0.48	<.001	0.66	0.001
HLF	0.42	<.001	0.55	<.001
HNF1B	0.67	0.006	0.74	0.010
HPS1	0.66	0.001	0.65	<.001
HSP90AB1	0.75	0.042
HSPA5	0.70	0.011
HSPB2	0.52	<.001	0.70	0.004
IGF1	0.35	<.001	0.59	<.001
IGF2	0.48	<.001	0.70	0.005
IGFBP2	0.61	<.001	0.77	0.044
IGFBP5	0.63	<.001
IGFBP6	0.45	<.001	0.64	<.001
IL6ST	0.55	0.004	0.63	<.001
ILK	0.40	<.001	0.57	<.001
ING5	0.56	<.001	0.78	0.033
ITGA1	0.56	0.004	0.61	<.001
ITGA3			0.78	0.035
ITGA5	0.71	0.019	0.75	0.017
ITGA7	0.37	<.001	0.52	<.001
ITGB3	0.63	0.003	0.70	0.005
ITPR1	0.46	<.001	0.64	<.001
ITPR3	0.70	0.013
ITSN1	0.62	0.001
JUN	0.48	<.001	0.60	<.001
JUNB	0.72	0.025
KIT	0.51	<.001	0.68	0.007
KLC1	0.58	<.001
KLK1	0.69	0.028	0.66	0.003
KLK2	0.60	<.001
KLK3	0.63	<.001	0.69	0.012
KRT15	0.56	<.001	0.60	<.001
KRT18	0.74	0.034
KRT5	0.64	<.001	0.62	<.001
LAMA4	0.47	<.001	0.73	0.010
LAMB3	0.73	0.018	0.69	0.003
LGALS3	0.59	0.003	0.54	<.001
LIG3	0.75	0.044
MAP3K7	0.66	0.003	0.79	0.031
MCM3	0.73	0.013	0.80	0.034
MGMT	0.61	0.001	0.71	0.007
MGST1			0.75	0.017
MLXIP	0.70	0.013
MMP2	0.57	<.001	0.72	0.010
MMP7	0.69	0.009
MPPED2	0.70	0.009	0.59	<.001
MSH6	0.78	0.046
MTA1	0.69	0.007
MTSS1	0.55	<.001	0.54	<.001
MYBPC1	0.45	<.001	0.45	<.001
NCAM1	0.51	<.001	0.65	<.001
NCAPD3	0.42	<.001	0.53	<.001
NCOR2	0.68	0.002
NDUFS5	0.66	0.001	0.70	0.013
NEXN	0.48	<.001	0.62	<.001
NFAT5	0.55	<.001	0.67	0.001
NFKBIA			0.79	0.048
NRG1	0.58	0.001	0.62	0.001
OLFML3	0.42	<.001	0.58	<.001
OMD	0.67	0.004	0.71	0.004
OR51E2	0.65	<.001	0.76	0.007
PAGE4	0.27	<.001	0.46	<.001
PCA3	0.68	0.004
PCDHGB7	0.70	0.025	0.65	<.001
PGF	0.62	0.001
PGR	0.63	0.028
PHTF2	0.69	0.033
PLP2	0.54	<.001	0.71	0.003
PPAP2B	0.41	<.001	0.54	<.001
PPP1R12A	0.48	<.001	0.60	<.001
PRIMA1	0.62	0.003	0.65	<.001
PRKAR1B	0.70	0.009
PRKAR2B			0.79	0.038
PRKCA	0.37	<.001	0.55	<.001
PRKCB	0.47	<.001	0.56	<.001
PTCH1	0.70	0.021
PTEN	0.66	0.010	0.64	<.001
PTGER3			0.76	0.015
PTGS2	0.70	0.013	0.68	0.005
PTH1R	0.48	<.001
PTK2B	0.67	0.014	0.69	0.002
PYCARD	0.72	0.023
RAB27A			0.76	0.017
RAGE	0.77	0.040	0.57	<.001
RARB	0.66	0.002	0.69	0.002
RECK	0.65	<.001
RHOA	0.73	0.043
RHOB	0.61	0.005	0.62	<.001
RND3	0.63	0.006	0.66	<.001
SDHC			0.69	0.002
SEC23A	0.61	<.001	0.74	0.010
SEMA3A	0.49	<.001	0.55	<.001
SERPINA3	0.70	0.034	0.75	0.020
SH3RF2	0.33	<.001	0.42	<.001
SLC22A3	0.23	<.001	0.37	<.001
SMAD4	0.33	<.001	0.39	<.001
SMARCC2	0.62	0.003	0.74	0.008
SMO	0.53	<.001	0.73	0.009
SORBS1	0.40	<.001	0.55	<.001
SPARCL1	0.42	<.001	0.63	<.001
SRD5A2	0.28	<.001	0.37	<.001
ST5	0.52	<.001	0.63	<.001
STAT5A	0.60	<.001	0.75	0.020
STAT5B	0.54	<.001	0.65	<.001
STS			0.78	0.035
SUMO1	0.75	0.017	0.71	0.002
SVIL	0.45	<.001	0.62	<.001
TARP	0.72	0.017
TGFB1I1	0.37	<.001	0.53	<.001
TGFB2	0.61	0.025	0.59	<.001
TGFB3	0.46	<.001	0.60	<.001
TIMP2	0.62	0.001
TIMP3	0.55	<.001	0.76	0.019
TMPRSS2	0.71	0.014
TNF	0.65	0.010
TNFRSF10A	0.71	0.014	0.74	0.010
TNFRSF10B	0.74	0.030	0.73	0.016
TNFSF10			0.69	0.004
TP53			0.73	0.011
TP63	0.62	<.001	0.68	0.003
TPM1	0.43	<.001	0.47	<.001
TPM2	0.30	<.001	0.47	<.001
TPP2	0.58	<.001	0.69	0.001
TRA2A	0.71	0.006
TRAF3IP2	0.50	<.001	0.63	<.001
TRO	0.40	<.001	0.59	<.001
TRPC6	0.73	0.030
TRPV6			0.80	0.047
VCL	0.44	<.001	0.55	<.001
VEGFB	0.73	0.029
VIM	0.72	0.013
VTI1B	0.78	0.046
WDR19	0.65	<.001
WFDC1	0.50	<.001	0.72	0.010
YY1	0.75	0.045
ZFHX3	0.52	<.001	0.54	<.001
ZFP36	0.65	0.004	0.69	0.012
ZNF827	0.59	<.001	0.69	0.004

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

TABLE 4A

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
Primary	Highest	Primary	Highest
Pattern	Pattern	Pattern	Pattern

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

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)

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

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)

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

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	bRFI
Official	Primary Pattern	Highest Pattern	Primary Pattern	Highest Pattern

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

AAMP	0.535	<.001	0.581	<.001	0.700	0.002	0.759	0.006
ABCA5	0.798	0.007	0.745	0.002			0.841	0.037
ABCC1			0.800	0.044
ABCC4			0.787	0.022
ABHD2			0.768	0.023
ACOX2	0.678	0.002	0.749	0.027	0.759	0.004
ADH5	0.645	<.001	0.672	0.001
AGTR1	0.780	0.030
AKAP1	0.815	0.045	0.758	<.001
AKT1			0.732	0.010
ALDH1A2	0.646	<.001	0.548	<.001	0.671	<.001	0.713	0.001
ANPEP	0.641	<.001	0.535	<.001
ANXA2	0.772	0.035			0.804	0.046
ATXN1	0.654	<.001	0.754	0.020	0.797	0.017
AURKA			0.788	0.030
AXIN2	0.744	0.005	0.655	<.001
AZGP1	0.656	<.001	0.676	<.001	0.754	0.001	0.791	0.004
BAD			0.700	0.004
BIN1	0.650	<.001	0.764	0.013	0.803	0.015
BTG3					0.836	0.025
BTRC	0.730	0.005
C7	0.617	<.001	0.680	<.001	0.667	<.001	0.755	0.005
CADM1	0.559	<.001	0.566	<.001	0.772	0.020	0.802	0.046
CASP1	0.781	0.030	0.779	0.021	0.818	0.027	0.828	0.036
CAV1					0.775	0.034
CAV2			0.677	0.019
CCL2			0.752	0.023
CCNH	0.679	<.001	0.682	<.001
CD164	0.721	0.002	0.724	0.005
CD1A					0.710	0.014
CD44	0.591	<.001	0.642	<.001
CD82	0.779	0.021	0.771	0.024
CDC25B	0.778	0.035			0.818	0.023
CDK14	0.788	0.011
CDK3	0.752	0.012			0.779	0.005	0.841	0.020
CDKN1A	0.770	0.049	0.712	0.014
CDKN1C	0.684	<.001			0.697	<.001
CHN1	0.772	0.031
COL6A1	0.648	<.001	0.807	0.046	0.768	0.004
CSF1	0.621	<.001	0.671	0.001
CTNNB1					0.905	0.008
CTSB	0.754	0.030	0.716	0.011	0.756	0.014
CXCL12	0.641	<.001	0.796	0.038	0.708	<.001
CYP3A5	0.503	<.001	0.528	<.001	0.791	0.028
CYR61	0.639	0.001	0.659	0.001			0.797	0.048
DARC					0.707	0.004
DDR2					0.750	0.011
DES	0.657	<.001	0.758	0.022	0.699	<.001
DHRS9	0.625	0.002
DHX9	0.846	<.001
DIAPH1	0.682	0.007	0.723	0.008	0.780	0.026
DLC1	0.703	0.005	0.702	0.008
DLGAP1	0.703	0.008	0.636	<.001
DNM3	0.701	0.001			0.817	0.042
DPP4	0.686	<.001	0.716	0.001
DPT	0.636	<.001	0.633	<.001	0.709	0.006	0.773	0.024
DUSP1	0.683	0.006	0.679	0.003
DUSP6	0.694	0.003	0.605	<.001
EDN1					0.773	0.031
EDNRA	0.716	0.007
EGR1	0.575	<.001	0.575	<.001			0.771	0.014
EGR3	0.633	0.002	0.643	<.001			0.792	0.025
EIF4E	0.722	0.002
ELK4	0.710	0.009	0.759	0.027
ENPP2	0.786	0.039
EPHA2			0.593	0.001
EPHA3	0.739	0.006			0.802	0.020
ERBB2			0.753	0.007
ERBB3	0.753	0.009	0.753	0.015
ERCC1							0.727	0.001
EREG					0.722	0.012	0.769	0.040
ESR1			0.742	0.015
FABP5	0.756	0.032
FAM107A	0.524	<.001	0.579	<.001	0.688	<.001	0.699	0.001
FAM13C	0.639	<.001	0.601	<.001	0.810	0.019	0.709	<.001
FAS	0.770	0.033
FASLG	0.716	0.028	0.683	0.017
FGF10					0.798	0.045
FGF17			0.718	0.018	0.793	0.024	0.790	0.024
FGFR2	0.739	0.007	0.783	0.038	0.740	0.004
FGFR4			0.746	0.050
FKBP5			0.689	0.003
FLNA	0.701	0.006	0.766	0.029	0.768	0.037
FLNC					0.755	<.001	0.820	0.022
FLT1			0.729	0.008
FOS	0.572	<.001	0.536	<.001			0.750	0.005
FOXQ1	0.778	0.033			0.820	0.018
FYN	0.708	0.006
GADD45B	0.577	<.001	0.589	<.001
GDF15	0.757	0.013	0.743	0.006
GHR			0.712	0.004			0.679	0.001
GNRH1					0.791	0.048
GPM6B	0.675	<.001	0.660	<.001	0.735	<.001	0.823	0.049
GSK3B	0.783	0.042
GSN	0.587	<.001	0.705	0.002	0.745	0.004	0.796	0.021
GSTM1	0.686	0.001	0.631	<.001	0.807	0.018
GSTM2	0.607	<.001	0.683	<.001	0.679	<.001	0.800	0.027
HIRIP3	0.692	<.001			0.782	0.007
HK1	0.724	0.002	0.718	0.002
HLF	0.580	<.001	0.571	<.001	0.759	0.008	0.750	0.004
HNF1B			0.669	<.001
HPS1	0.764	0.008
HSD17B10	0.802	0.045
HSD17B2					0.723	0.048
HSD3B2							0.709	0.010
HSP90AB1	0.780	0.034			0.809	0.041
HSPA5			0.738	0.017
HSPB1	0.770	0.006	0.801	0.032
HSPB2					0.788	0.035
ICAM1	0.728	0.015	0.716	0.010
IER3	0.735	0.016	0.637	<.001			0.802	0.035
IFIT1	0.647	<.001	0.755	0.029
IGF1	0.675	<.001	0.603	<.001	0.762	0.006	0.770	0.030
IGF2					0.761	0.011
IGFBP2	0.601	<.001	0.605	<.001
IGFBP5	0.702	<.001
IGFBP6	0.628	<.001			0.726	0.003
IL1B	0.676	0.002	0.716	0.004
IL6	0.688	0.005	0.766	0.044
IL6R			0.786	0.036
IL6ST	0.618	<.001	0.639	<.001	0.785	0.027	0.813	0.042
IL8	0.635	<.001	0.628	<.001
ILK	0.734	0.018	0.753	0.026
ING5	0.684	<.001	0.681	<.001	0.756	0.006
ITGA4	0.778	0.040
ITGA5	0.762	0.026
ITGA6			0.811	0.038
ITGA7	0.592	<.001	0.715	0.006	0.710	0.002
ITGAD			0.576	0.006
ITGB4			0.693	0.003
ITPR1	0.789	0.029
JUN	0.572	<.001	0.581	<.001			0.777	0.019
JUNB	0.732	0.030	0.707	0.016
KCTD12	0.758	0.036
KIT					0.691	0.009	0.738	0.028
KLC1	0.741	0.024			0.781	0.024
KLF6	0.733	0.018	0.727	0.014
KLK1			0.744	0.028
KLK2	0.697	0.002	0.679	<.001
KLK3	0.725	<.001	0.715	<.001			0.841	0.023
KRT15	0.660	<.001	0.577	<.001	0.750	0.002
KRT18	0.623	<.001	0.642	<.001	0.702	<.001	0.760	0.006
KRT2					0.740	0.044
KRT5	0.674	<.001	0.588	<.001	0.769	0.005
KRT8	0.768	0.034
L1CAM	0.737	0.036
LAG3	0.711	0.013	0.748	0.029
LAMA4					0.649	0.009
LAMB3	0.709	0.002	0.684	0.006	0.768	0.006
LGALS3	0.652	<.001	0.752	0.015	0.805	0.028
LIG3	0.728	0.016	0.667	<.001
LRP1							0.811	0.043
MDM2			0.788	0.033
MGMT	0.645	<.001	0.766	0.015
MICA	0.796	0.043	0.676	<.001
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

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)

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

AKR1C3	1.258	0.039
ANLN	1.292	0.023			1.449	<.001	1.420	0.001
AQP2	1.178	0.008	1.287	<.001
ASAP2			1.396	0.015
ASPN	1.809	<.001	1.508	0.009	1.506	0.002	1.438	0.002
BAG5			1.367	0.012
BAX							1.234	0.044
BGN	1.465	0.009	1.342	0.046
BIRC5	1.338	0.008			1.364	0.004	1.279	0.006
BMP6	1.369	0.015	1.518	0.002
BUB1	1.239	0.024	1.227	0.001	1.236	0.004
CACNA1D			1.337	0.025
CADPS					1.280	0.029
CCNE2			1.256	0.043	1.577	<.001	1.324	0.001
CD276	1.320	0.029	1.396	0.007	1.279	0.033
CDC20	1.298	0.016	1.334	0.002	1.257	0.032	1.279	0.003
CDH7	1.258	0.047	1.338	0.013
CDKN2B	1.342	0.032	1.488	0.009
CDKN2C	1.344	0.010	1.450	<.001
CDKN3	1.284	0.012
CENPF	1.289	0.048			1.498	0.001	1.344	0.010
COL1A1	1.481	0.003	1.506	0.002
COL3A1	1.459	0.004	1.430	0.013
COL4A1	1.396	0.015
COL8A1	1.413	0.008
CRISP3	1.346	0.012	1.310	0.025
CTHRC1			1.588	0.002
DDIT4	1.363	0.020	1.379	0.028
DICER1							1.294	0.008
ENY2					1.269	0.024
FADD			1.307	0.010
FAS							1.243	0.025
FGF5	1.328	0.002
GNPTAB							1.246	0.037
GREM1	1.332	0.024	1.377	0.013	1.373	0.011
HDAC1					1.301	0.018	1.237	0.021
HSD17B4							1.277	0.011
IFN-γ					1.219	0.048
IMMT					1.230	0.049
INHBA	1.866	<.001	1.944	<.001
JAG1			1.298	0.030
KCNN2			1.378	0.020			1.282	0.017
KHDRBS3			1.353	0.029	1.305	0.014
LAMA3					1.344	<.001	1.232	0.048
LAMC1	1.396	0.015
LIMS1							1.337	0.004
LOX					1.355	0.001	1.341	0.002
LTBP2			1.304	0.045
MAGEA4	1.215	0.024
MANF					1.460	<.001
MCM6			1.287	0.042			1.214	0.046
MELK					1.329	0.002
MMP11	1.281	0.050
MRPL13							1.266	0.021
MYBL2	1.453	<.001			1.274	0.019
MYC					1.265	0.037
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

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)

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

AAMP	0.660	0.001	0.675	<.001			0.836	0.045
ABCA5	0.807	0.014	0.737	<.001			0.845	0.030
ABCC1	0.780	0.038	0.794	0.015
ABCG2							0.807	0.035
ABHD2			0.720	0.002
ADH5	0.750	0.034
AKAP1			0.721	<.001
ALDH1A2	0.735	0.009	0.592	<.001	0.756	0.007	0.781	0.021
ANGPT2					0.741	0.036
ANPEP	0.637	<.001	0.536	<.001
ANXA2			0.762	0.044
APOE			0.707	0.013
APRT			0.727	0.004			0.771	0.006
ATXN1	0.725	0.013
AURKA	0.784	0.037	0.735	0.003
AXIN2	0.744	0.004	0.630	<.001
AZGP1	0.672	<.001	0.720	<.001	0.764	0.001
BAD			0.687	<.001
BAK1			0.783	0.014
BCL2	0.777	0.033	0.772	0.036
BIK			0.768	0.040
BIN1	0.691	<.001
BTRC			0.776	0.029
C7	0.707	0.004			0.791	0.024
CADM1	0.587	<.001	0.593	<.001
CASP1	0.773	0.023			0.820	0.025
CAV1					0.753	0.014
CAV2			0.627	0.009			0.682	0.003
CCL2			0.740	0.019
CCNH	0.736	0.003
CCR1			0.755	0.022
CD1A					0.740	0.025
CD44	0.590	<.001	0.637	<.001
CD68	0.757	0.026
CD82	0.778	0.012	0.759	0.016
CDC25B	0.760	0.021
CDK3	0.762	0.024			0.774	0.007
CDKN1A			0.714	0.015
CDKN1C	0.738	0.014			0.768	0.021
COL6A1	0.690	<.001	0.805	0.048
CSF1	0.675	0.002	0.779	0.036
CSK					0.825	0.004
CTNNB1	0.884	0.045			0.888	0.027
CTSB	0.740	0.017	0.676	0.003	0.755	0.010
CTSD	0.673	0.031	0.722	0.009
CTSK					0.804	0.034
CTSL2			0.748	0.019
CXCL12	0.731	0.017
CYP3A5	0.523	<.001	0.518	<.001
CYR61	0.744	0.041
DAP					0.755	0.011
DARC					0.763	0.029
DDR2							0.813	0.041
DES	0.743	0.020
DHRS9	0.606	0.001
DHX9	0.916	0.021
DIAPH1	0.749	0.036	0.688	0.003
DLGAP1	0.758	0.042	0.676	0.002
DLL4							0.779	0.010
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

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		Highest
	Pattern		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

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		Highest
	Pattern		Pattern

	Official Symbol	HR	p-value	HR	p-value

AAMP	0.56	<.001	0.65	0.001
ABCA5	0.64	<.001	0.71	<.001
ABCB1	0.62	0.004
ABCC3			0.74	0.031
ABCG2			0.78	0.050
ABHD2	0.71	0.035
ACOX2	0.54	<.001	0.71	0.007
ADH5	0.49	<.001	0.61	<.001
AKAP1	0.77	0.031	0.76	0.013
AKR1C1	0.65	0.006	0.78	0.044
AKT1			0.72	0.020
AKT3	0.75	<.001
ALDH1A2	0.53	<.001	0.60	<.001
AMPD3	0.62	<.001	0.78	0.028
ANPEP	0.54	<.001	0.61	<.001
ANXA2	0.63	0.008	0.74	0.016
ARHGAP29	0.67	0.005	0.77	0.016
ARHGDIB	0.64	0.013
ATP5J	0.57	0.050
ATXN1	0.61	0.004	0.77	0.043
AXIN2	0.51	<.001	0.62	<.001
AZGP1	0.61	<.001	0.64	<.001
BCL2	0.64	0.004	0.75	0.029
BIN1	0.52	<.001	0.74	0.010
BTG3	0.75	0.032	0.75	0.010
BTRC	0.69	0.011
C7	0.51	<.001	0.67	<.001
CADM1	0.49	<.001	0.76	0.034
CASP1	0.71	0.010	0.74	0.007
CAV1			0.73	0.015
CCL5	0.67	0.018	0.67	0.003
CCNH	0.63	<.001	0.75	0.004
CCR1			0.77	0.032
CD164	0.52	<.001	0.63	<.001
CD44	0.53	<.001	0.74	0.014
CDH10	0.69	0.040
CDH18	0.40	0.011
CDK14	0.75	0.013
CDK2			0.81	0.031
CDK3	0.73	0.022
CDKN1A	0.68	0.038
CDKN1C	0.62	0.003	0.72	0.005
COL6A1	0.54	<.001	0.70	0.004
COL6A3	0.64	0.004
CSF1	0.56	<.001	0.78	0.047
CSRP1	0.40	<.001	0.66	0.002
CTGF	0.66	0.015	0.74	0.027
CTNNB1	0.69	0.043
CTSB	0.60	0.002	0.71	0.011
CTSS	0.67	0.013
CXCL12	0.56	<.001	0.77	0.026
CYP3A5	0.43	<.001	0.63	<.001
CYR61	0.43	<.001	0.58	<.001
DAG1			0.72	0.012
DARC	0.66	0.016
DDR2	0.65	0.007
DES	0.52	<.001	0.74	0.018
DHRS9	0.54	0.007
DICER1	0.70	0.044
DLC1			0.75	0.021
DLGAP1	0.55	<.001	0.72	0.005
DNM3	0.61	0.001
DPP4	0.55	<.001	0.77	0.024
DPT	0.48	<.001	0.61	<.001
DUSP1	0.47	<.001	0.59	<.001
DUSP6	0.65	0.009	0.65	0.002
DYNLL1			0.74	0.045
EDNRA	0.61	0.002	0.75	0.038
EFNB2	0.71	0.043
EGR1	0.43	<.001	0.58	<.001
EGR3	0.47	<.001	0.66	<.001
EIF5			0.77	0.028
ELK4	0.49	<.001	0.72	0.012
EPHA2			0.70	0.007
EPHA3	0.62	<.001	0.72	0.009
EPHB2	0.68	0.009
ERBB2	0.64	<.001	0.63	<.001
ERBB3	0.69	0.018
ERCC1	0.69	0.019	0.77	0.021
ESR2	0.61	0.020
FAAH	0.57	<.001	0.77	0.035
FABP5	0.67	0.035
FAM107A	0.42	<.001	0.59	<.001
FAM13C	0.53	<.001	0.59	<.001
FAS	0.71	0.035
FASLG	0.56	0.017	0.67	0.014
FGF10	0.57	0.002
FGF17	0.70	0.039	0.70	0.010
FGF7	0.63	0.005	0.70	0.004
FGFR2	0.63	0.003	0.71	0.003
FKBP5			0.72	0.020
FLNA	0.48	<.001	0.74	0.022
FOS	0.45	<.001	0.56	<.001
FOXO1	0.59	<.001
FOXQ1	0.57	<.001	0.69	0.008
FYN	0.62	0.001	0.74	0.013
G6PD			0.77	0.014
GADD45A	0.73	0.045
GADD45B	0.45	<.001	0.64	0.001
GDF15	0.58	<.001
GHR	0.62	0.008	0.68	0.002
GPM6B	0.60	<.001	0.70	0.003
GSK3B	0.71	0.016	0.71	0.006
GSN	0.46	<.001	0.66	<.001
GSTM1	0.56	<.001	0.62	<.001
GSTM2	0.47	<.001	0.67	<.001
HGD			0.72	0.002
HIRIP3	0.69	0.021	0.69	0.002
HK1	0.68	0.005	0.73	0.005
HLA-G	0.54	0.024	0.65	0.013
HLF	0.41	<.001	0.68	0.001
HNF1B	0.55	<.001	0.59	<.001
HPS1	0.74	0.015	0.76	0.025
HSD17B3	0.65	0.031
HSPB2	0.62	0.004	0.76	0.027
ICAM1	0.61	0.010
IER3	0.55	<.001	0.67	0.003
IFIT1	0.57	<.001	0.70	0.008
IFNG			0.69	0.040
IGF1	0.63	<.001	0.59	<.001
IGF2	0.67	0.019	0.70	0.005
IGFBP2	0.53	<.001	0.63	<.001
IGFBP5	0.57	<.001	0.71	0.006
IGFBP6	0.41	<.001	0.71	0.012
IL10	0.59	0.020
IL1B	0.53	<.001	0.70	0.005
IL6	0.55	0.001
IL6ST	0.45	<.001	0.68	<.001
IL8	0.60	0.005	0.70	0.008
ILK	0.68	0.029	0.76	0.036
ING5	0.54	<.001	0.82	0.033
ITGA1	0.66	0.017
ITGA3	0.70	0.020
ITGA5	0.64	0.011
ITGA6	0.66	0.003	0.74	0.006
ITGA7	0.50	<.001	0.71	0.010
ITGB4	0.63	0.014	0.73	0.010
ITPR1	0.55	<.001
ITPR3			0.76	0.007
JUN	0.37	<.001	0.54	<.001
JUNB	0.58	0.002	0.71	0.016
KCTD12	0.68	0.017
KIT	0.49	0.002	0.76	0.043
KLC1	0.61	0.005	0.77	0.045
KLF6	0.65	0.009
KLK1	0.68	0.036
KLK10			0.76	0.037
KLK2	0.64	<.001	0.73	0.006
KLK3	0.65	<.001	0.76	0.021
KLRK1	0.63	0.005
KRT15	0.52	<.001	0.58	<.001
KRT18	0.46	<.001
KRT5	0.51	<.001	0.58	<.001
KRT8	0.53	<.001
L1CAM	0.65	0.031
LAG3	0.58	0.002	0.76	0.033
LAMA4	0.52	0.018
LAMB3	0.60	0.002	0.65	0.003
LGALS3	0.52	<.001	0.71	0.002
LIG3	0.65	0.011
LRP1	0.61	0.001	0.75	0.040
MGMT	0.66	0.003
MICA	0.59	0.001	0.68	0.001
MLXIP	0.70	0.020
MMP2	0.68	0.022
MMP9	0.67	0.036
MPPED2	0.57	<.001	0.66	<.001
MRC1	0.69	0.028
MTSS1	0.63	0.005	0.79	0.037
MVP	0.62	<.001
MYBPC1	0.53	<.001	0.70	0.011
NCAM1	0.70	0.039	0.77	0.042
NCAPD3	0.52	<.001	0.59	<.001
NDRG1			0.69	0.008
NEXN	0.62	0.002
NFAT5	0.45	<.001	0.59	<.001
NFATC2	0.68	0.035	0.75	0.036
NFKBIA	0.70	0.030
NRG1	0.59	0.022	0.71	0.018
OAZ1	0.69	0.018	0.62	<.001
OLFML3	0.59	<.001	0.72	0.003
OR51E2	0.73	0.013
PAGE4	0.42	<.001	0.62	<.001
PCA3	0.53	<.001
PCDHGB7	0.70	0.032
PGF	0.68	0.027	0.71	0.013
PGR			0.76	0.041
PIK3C2A			0.80	<.001
PIK3CA	0.61	<.001	0.80	0.036
PIK3CG	0.67	0.001	0.76	0.018
PLP2	0.65	0.015	0.72	0.010
PPAP2B	0.45	<.001	0.69	0.003
PPP1R12A	0.61	0.007	0.73	0.017
PRIMA1	0.51	<.001	0.68	0.004
PRKCA	0.55	<.001	0.74	0.009
PRKCB	0.55	<.001
PROM1			0.67	0.042
PROS1	0.73	0.036
PTCH1	0.69	0.024	0.72	0.010
PTEN	0.54	<.001	0.64	<.001
PTGS2	0.48	<.001	0.55	<.001
PTH1R	0.57	0.003	0.77	0.050
PTHLH	0.55	0.010
PTK2B	0.56	<.001	0.70	0.001
PYCARD			0.73	0.009
RAB27A	0.65	0.009	0.71	0.014
RAB30	0.59	0.003	0.72	0.010
RAGE			0.76	0.011
RARB	0.59	<.001	0.63	<.001
RASSF1	0.67	0.003
RB1	0.67	0.006
RFX1	0.71	0.040	0.70	0.003
RHOA	0.71	0.038	0.65	<.001
RHOB	0.58	0.001	0.71	0.006
RND3	0.54	<.001	0.69	0.003
RNF114	0.59	0.004	0.68	0.003
SCUBE2			0.77	0.046
SDHC	0.72	0.028	0.76	0.025
SEC23A			0.75	0.029
SEMA3A	0.61	0.004	0.72	0.011
SEPT9	0.66	0.013	0.76	0.036
SERPINB5			0.75	0.039
SH3RF2	0.44	<.001	0.48	<.001
SHH			0.74	0.049
SLC22A3	0.42	<.001	0.61	<.001
SMAD4	0.45	<.001	0.66	<.001
SMARCD1	0.69	0.016
SOD1	0.68	0.042
SORBS1	0.51	<.001	0.73	0.012
SPARCL1	0.58	<.001	0.77	0.040
SPDEF	0.77	<.001
SPINT1	0.65	0.004	0.79	0.038
SRC	0.61	<.001	0.69	0.001
SRD5A2	0.39	<.001	0.55	<.001
ST5	0.61	<.001	0.73	0.012
STAT1	0.64	0.006
STAT3	0.63	0.010
STAT5A	0.62	0.001	0.70	0.003
STAT5B	0.58	<.001	0.73	0.009
SUMO1	0.66	<.001
SVIL	0.57	0.001	0.74	0.022
TBP	0.65	0.002
TFF1	0.65	0.021
TFF3	0.58	<.001
TGFB1I1	0.51	<.001	0.75	0.026
TGFB2	0.48	<.001	0.62	<.001
TGFBR2	0.61	0.003
TIAM1	0.68	0.019
TIMP2	0.69	0.020
TIMP3	0.58	0.002
TNFRSF10A	0.73	0.047
TNFRSF10B	0.47	<.001	0.70	0.003
TNFSF10	0.56	0.001
TP63			0.67	0.001
TPM1	0.58	0.004	0.73	0.017
TPM2	0.46	<.001	0.70	0.005
TRA2A	0.68	0.013
TRAF3IP2	0.73	0.041	0.71	0.004
TRO	0.72	0.016	0.71	0.004
TUBB2A	0.53	<.001	0.73	0.021
TYMP	0.70	0.011
VCAM1	0.69	0.041
VCL	0.46	<.001
VEGFA			0.77	0.039
VEGFB	0.71	0.035
VIM	0.60	0.001
XRCC5			0.75	0.026
YY1	0.62	0.008	0.77	0.039
ZFHX3	0.53	<.001	0.58	<.001
ZFP36	0.43	<.001	0.54	<.001
ZNF827	0.55	0.001

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

TABLE 8A

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		Highest
	Pattern		Pattern

	Official Symbol	HR	p-value	HR	p-value

ACTR2	1.78	0.017
AKR1C3	1.44	0.013
ALCAM			1.44	0.022
ANLN	1.37	0.046	1.81	<.001
APOE	1.49	0.023	1.66	0.005
AQP2			1.30	0.013
ARHGDIB	1.55	0.021
ASPN	2.13	<.001	2.43	<.001
ATP5E	1.69	0.013	1.58	0.014
BGN	1.92	<.001	2.55	<.001
BIRC5	1.48	0.006	1.89	<.001
BMP6	1.51	0.010	1.96	<.001
BRCA2			1.41	0.007
BUB1	1.36	0.007	1.52	<.001
CCNE2	1.55	0.004	1.59	<.001
CD276			1.65	<.001
CDC20	1.68	<.001	1.74	<.001
CDH11			1.50	0.017
CDH18	1.36	<.001
CDH7	1.54	0.009	1.46	0.026
CDKN2B	1.68	0.008	1.93	0.001
CDKN2C	2.01	<.001	1.77	<.001
CDKN3	1.51	0.002	1.33	0.049
CENPF	1.51	0.007	2.04	<.001
CKS2	1.43	0.034	1.56	0.007
COL1A1	2.23	<.001	3.04	<.001
COL1A2	1.79	0.001	2.22	<.001
COL3A1	1.96	<.001	2.81	<.001
COL4A1			1.52	0.020
COL5A1			1.50	0.020
COL5A2	1.64	0.017	1.55	0.010
COL8A1	1.96	<.001	2.38	<.001
CRISP3	1.68	0.002	1.67	0.002
CTHRC1			2.06	<.001
CTNND2	1.42	0.046	1.50	0.025
CTSK			1.43	0.049
CXCR4	1.82	0.001	1.64	0.007
DDIT4	1.54	0.016	1.58	0.009
DLL4			1.51	0.007
DYNLL1	1.50	0.021	1.22	0.002
F2R	2.27	<.001	2.02	<.001
FAP			2.12	<.001
FCGR3A			1.94	0.002
FGF5	1.23	0.047
FOXP3	1.52	0.006	1.48	0.018
GNPTAB			1.44	0.042
GPR68			1.51	0.011
GREM1	1.91	<.001	2.38	<.001
HDAC1			1.43	0.048
HDAC9	1.65	<.001	1.67	0.004
HRAS	1.65	0.005	1.58	0.021
IGFBP3	1.94	<.001	1.85	<.001
INHBA	2.03	<.001	2.64	<.001
JAG1	1.41	0.027	1.50	0.008
KCTD12			1.51	0.017
KHDRBS3	1.48	0.029	1.54	0.014
KPNA2			1.46	0.050
LAMA3	1.35	0.040
LAMC1	1.77	0.012
LTBP2			1.82	<.001
LUM	1.51	0.021	1.53	0.009
MELK	1.38	0.020	1.49	0.001
MKI67			1.37	0.014
MMP11	1.73	<.001	1.69	<.001
MRPL13			1.30	0.046
MYBL2	1.56	<.001	1.72	<.001
MYLK3			1.17	0.007
NOX4	1.58	0.005	1.96	<.001
NRIP3			1.30	0.040
NRP1			1.53	0.021
OLFML2B			1.54	0.024
OSM	1.43	0.018
PATE1	1.20	<.001	1.33	<.001
PCNA			1.64	0.003
PEX10	1.41	0.041	1.64	0.003
PIK3CA	1.38	0.037
PLK1	1.52	0.009	1.67	0.002
PLOD2			1.65	0.002
POSTN	1.79	<.001	2.06	<.001
PTK6	1.67	0.002	2.38	<.001
PTTG1	1.56	0.002	1.54	0.003
RAD21	1.61	0.036	1.53	0.005
RAD51			1.33	0.009
RALA	1.95	0.004	1.60	0.007
REG4			1.43	0.042
ROBO2	1.46	0.024
RRM1			1.44	0.033
RRM2	1.50	0.003	1.48	<.001
SAT1	1.42	0.009	1.43	0.012
SEC14L1			1.64	0.002
SFRP4	2.07	<.001	2.40	<.001
SHMT2	1.52	0.030	1.60	0.001
SLC44A1			1.42	0.039
SPARC	1.93	<.001	2.21	<.001
SULF1	1.63	0.006	2.04	<.001
THBS2	1.95	<.001	2.26	<.001
THY1	1.69	0.016	1.95	0.002
TK1			1.43	0.003
TOP2A	1.57	0.002	2.11	<.001
TPX2	1.84	<.001	2.27	<.001
UBE2C	1.41	0.011	1.44	0.006
UBE2T	1.63	0.001
UHRF1	1.51	0.007	1.69	<.001
WISP1	1.47	0.045
WNT5A	1.35	0.027	1.63	0.001
ZWINT	1.36	0.045

TABLE 8B

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		Highest
	Pattern		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

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

Table 9B. Genes significantly (p < 0.05) associated with TMPRSS
fusion status in the primary Gleason pattern with odds ratio (OR) < 1.0
(increased expression is negatively associated with TMPRSS fusion
positivity)

	Official Symbol	p-value	Odds Ratio

ABCC4	0.045	0.77
ABHD2	<.001	0.38
ACTR2	0.027	0.73
ADAMTS1	0.024	0.58
ADH5	<.001	0.58
AGTR2	0.016	0.64
AKAP1	0.013	0.70
AKT2	0.015	0.71
ALCAM	<.001	0.45
ALDH1A2	0.004	0.70
ANPEP	<.001	0.43
ANXA2	0.010	0.71
APC	0.036	0.73
APOC1	0.002	0.56
APOE	<.001	0.44
ARF1	0.041	0.77
ATM	0.036	0.74
AURKB	<.001	0.62
AZGP1	<.001	0.54
BBC3	0.030	0.74
BCL2	0.012	0.70
BIN1	0.021	0.74
BTG1	0.004	0.67
BTG3	0.003	0.63
C7	0.023	0.74
CADM1	0.007	0.69
CASP1	0.011	0.70
CAV1	0.011	0.71
CCND1	0.019	0.72
CCR1	0.022	0.73
CD44	<.001	0.57
CD68	<.001	0.54
CD82	0.002	0.66
CDH5	0.007	0.66
CDKN1A	<.001	0.60
CDKN2B	<.001	0.54
CDKN2C	0.012	0.72
CDKN3	0.037	0.77
CHN1	0.038	0.75
CKS2	<.001	0.48
COL11A1	0.017	0.72
COL1A1	<.001	0.59
COL1A2	0.001	0.62
COL3A1	0.027	0.73
COL4A1	0.043	0.76
COL5A1	0.039	0.74
COL5A2	0.026	0.73
COL6A1	0.008	0.66
COL6A3	<.001	0.59
COL8A1	0.022	0.74
CSF1	0.011	0.70
CTNNB1	0.021	0.69
CTSB	<.001	0.62
CTSD	0.036	0.68
CTSK	0.007	0.70
CTSS	0.002	0.64
CXCL12	<.001	0.48
CXCR4	0.005	0.68
CXCR7	0.046	0.76
CYR61	0.004	0.65
DAP	0.002	0.64
DARC	0.021	0.73
DDR2	0.021	0.73
DHRS9	<.001	0.52
DIAPH1	<.001	0.56
DICER1	0.029	0.75
DLC1	0.013	0.72
DLGAP1	<.001	0.60
DLL4	<.001	0.57
DPT	0.006	0.68
DUSP1	0.012	0.68
DUSP6	0.001	0.62
DVL1	0.037	0.75
EFNB2	<.001	0.32
EGR1	0.003	0.65
ELK4	<.001	0.60
ERBB2	<.001	0.61
ERBB3	0.045	0.76
ESR2	0.010	0.70
ETV1	0.042	0.74
FABP5	<.001	0.21
FAM13C	0.006	0.67
FCGR3A	0.018	0.72
FGF17	0.009	0.71
FGF6	0.011	0.70
FGF7	0.003	0.63
FN1	0.006	0.69
FOS	0.035	0.74
FOXP3	0.010	0.71
GABRG2	0.029	0.74
GADD45B	0.003	0.63
GDF15	<.001	0.54
GPM6B	0.004	0.67
GPNMB	0.001	0.62
GSN	0.009	0.69
HLA-G	0.050	0.74
HLF	0.018	0.74
HPS1	<.001	0.48
HSD17B3	0.003	0.60
HSD17B4	<.001	0.56
HSPB1	<.001	0.38
HSPB2	0.002	0.62
IFI30	0.049	0.75
IFNG	0.006	0.64
IGF1	0.016	0.73
IGF2	0.001	0.57
IGFBP2	<.001	0.51
IGFBP3	<.001	0.59
IGFBP6	<.001	0.57
IL10	<.001	0.62
IL17A	0.012	0.63
IL1A	0.011	0.59
IL2	0.001	0.63
IL6ST	<.001	0.52
INSL4	0.014	0.71
ITGA1	0.009	0.69
ITGA4	0.007	0.68
JUN	<.001	0.59
KIT	<.001	0.64
KRT76	0.016	0.70
LAG3	0.002	0.63
LAPTM5	<.001	0.58
LGALS3	<.001	0.53
LTBP2	0.011	0.71
LUM	0.012	0.70
MAOA	0.020	0.73
MAP4K4	0.007	0.68
MGST1	<.001	0.54
MMP2	<.001	0.61
MPPED2	<.001	0.45
MRC1	0.005	0.67
MTPN	0.002	0.56
MTSS1	<.001	0.53
MVP	0.009	0.72
MYBPC1	<.001	0.51
MYLK3	0.001	0.58
NCAM1	<.001	0.59
NCAPD3	<.001	0.40
NCOR1	0.004	0.69
NFKBIA	<.001	0.63
NNMT	0.006	0.66
NPBWR1	0.027	0.67
OAZ1	0.049	0.64
OLFML3	<.001	0.56
OSM	<.001	0.64
PAGE1	0.012	0.52
PDGFRB	0.016	0.73
PECAM1	<.001	0.55
PGR	0.048	0.77
PIK3CA	<.001	0.55
PIK3CG	0.008	0.71
PLAU	0.044	0.76
PLK1	0.006	0.68
PLOD2	0.013	0.71
PLP2	0.024	0.73
PNLIPRP2	0.009	0.70
PPAP2B	<.001	0.62
PRKAR2B	<.001	0.61
PRKCB	0.044	0.76
PROS1	0.005	0.67
PTEN	<.001	0.47
PTGER3	0.007	0.69
PTH1R	0.011	0.70
PTK2B	<.001	0.61
PTPN1	0.028	0.73
RAB27A	<.001	0.21
RAD51	<.001	0.51
RAD9A	0.030	0.75
RARB	<.001	0.62
RASSF1	0.038	0.76
RECK	0.009	0.62
RHOB	0.004	0.64
RHOC	<.001	0.56
RLN1	<.001	0.30
RND3	0.014	0.72
S100P	0.002	0.66
SDC2	<.001	0.61
SEMA3A	0.001	0.64
SMAD4	<.001	0.64
SPARC	<.001	0.59
SPARCL1	<.001	0.56
SPINK1	<.001	0.26
SRD5A1	0.039	0.76
STAT1	0.026	0.74
STS	0.006	0.64
SULF1	<.001	0.53
TFF3	<.001	0.19
TGFA	0.002	0.65
TGFB1I1	0.040	0.77
TGFB2	0.003	0.66
TGFB3	<.001	0.54
TGFBR2	<.001	0.61
THY1	<.001	0.63
TIMP2	0.004	0.66
TIMP3	<.001	0.60
TMPRSS2	<.001	0.40
TNFSF11	0.026	0.63
TPD52	0.002	0.64
TRAM1	<.001	0.45
TRPC6	0.002	0.64
TUBB2A	<.001	0.49
VCL	<.001	0.57
VEGFB	0.033	0.73
VEGFC	<.001	0.61
VIM	0.012	0.69
WISP1	0.030	0.75
WNT5A	<.001	0.50

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

TABLE 10A

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

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

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 Pattern	Primary Pattern	Highest 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

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

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

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

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 (C_p) 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-value^a	Direction	Uncorrected	Confidence	Bound	Corrected
MicroRNA	p-value	(FDR)	of Association^b	Estimate	Interval	@10% FDR	Estimate^c

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

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-value^a	Direction	Uncorrected	Confidence	@10%	Corrected
MicroRNA	p-value	(FDR)	of Association^b	Estimate	Interval	FDR	Estimate^c

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-value^a	Direction	Uncorrected	95% Confidence	@10%	RM-Corrected
MicroRNA	p-value	(FDR)	of Association^b	Estimate	Interval	FDR	Estimate^c

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

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

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

hsa-miR-30e-5p	0.0001	2.9%	(−)	1.97	(1.40, 2.78)	1.09	1.39
hsa-miR-30a	0.0002	3.3%	(−)	1.90	(1.36, 2.65)	1.08	1.38

^aThe q-value is the empirical Bayes probability that the microRNA's association with clinical recurrence is a false discovery, given the data.
^bDirection of association indicates where higher microRNA expression is associated with higher (+) or lower (−) risk of clinical recurrence.
^cRM: regression to the mean.

Accordingly, the normalized expression levels of hsa-miR-93; hsa-miR-106b; hsa-miR-21; hsa-miR-449a; hsa-miR-182; hsa-miR-27a; hsa-miR-103; hsa-miR-141; hsa-miR-92a; hsa-miR-22; hsa-miR-29b; hsa-miR-210; hsa-miR-331; hsa-miR-191; hsa-miR-425; and hsa-miR-200c are positively associated with an increased risk of recurrence; and hsa-miR-30e-5p; hsa-miR-133a; hsa-miR-30a; hsa-miR-222; hsa-miR-1; hsa-miR-145; hsa-miR-486-5p; hsa-miR-19b; hsa-miR-205; hsa-miR-31; hsa-miR-155; hsa-miR-206; hsa-miR-99a; and hsa-miR-146b-5p are negatively associated with an increased risk of recurrence.
Furthermore, the normalized expression levels of hsa-miR-106b; hsa-miR-21; hsa-miR-93; hsa-miR-331; hsa-miR-150; hsa-miR-27b; and hsa-miR-10a are positively associated with an increased risk of prostate cancer specific death; and the normalized expression levels of hsa-miR-30e-5p; hsa-miR-30a; hsa-miR-133a; hsa-miR-222; hsa-miR-1; hsa-miR-26a; and hsa-miR-152 are negatively associated with an increased risk of prostate cancer specific death.
Table 22 shows the number of microRNA-gene pairs that were grouped in each tier (Tiers 1-4) and the number and percentage of those that were predictive of clinical recurrence at a false discovery rate of 10%.

TABLE 22

		Number of Pairs Predictive of
	Total Number of	Clinical Recurrence at False
Tier	MicroRNA-Gene Pairs	Discovery Rate	10% (%)

Tier 1	80	46	(57.5%)
Tier 2	719	591	(82.2%)
Tier 3	3,850	2,792	(72.5%)
Tier 4	54,724	38,264	(69.9%)

TABLE A

		SEQ		SEQ		SEQ		SEQ
Official	Accession	ID	Forward	ID	Reverse	ID		ID
Symbol:	Number:	NO	Primer Sequence:	NO	Primer Sequence:	NO	Probe Sequence:	NO	Amplicon Sequence:

AAMP	NM_001087	1	GTGTGGCAGGTGGAC	2	CTCCATCCACTCCAGG	3	CGCTTCAAAGGACC	4	GTGTGGCAGGTGGACACTAAGGAGGAGGTCTGGTCCTTT
			ACTAA		TCTC		AGACCTCCTC		GAAGCGGGAGACCTGGAGTGGATGGAG

ABCA5	NM_172232	5	GGTATGGATCCCAAA	6	CAGCCCGCTTTCTGTT	7	CACATGTGGCAGAG	8	GGTATGGATCCCAAAGCCAAACAGCACATGTGGCGAGCA
			GCCA		TTTA		CAATTCGAACT		ATTCGAACTGCATTTAAAAACAGAAAGCGGGCT

ABCD1	NM_000927	9	AAACACCACTGGAGC	10	CAAGCCTGGAACCTAT	11	CAAGCCTGGAACCT	12	AAACACCACTGGAGCATTGACTACCAGGCTCGCCAATGA
			ATTGA		AGCC		ATAGCC		TGCTGCTCAAGTTAAAGGGGCTATAGGTTCCAG

ABCC1	NM_004996	13	TCATGGTGCCCGTCA	14	CGATTGTCTTTGCTCT	15	ACCTGATACGTCTT	16	TCATGGTGCCCGTCAATGCTGTGATGGCGATGAAGACCA
			ATG		TCATGTG		GGTCTTCATCGCCA		AGACGTATCAGGTGGCCCACATGAAGAGCAAAG
							T

ABCC3	NM_003786	17	TCATCCTGGCGATCT	18	CCGTTGAGTGGAATCA	19	TCTGTCCTGGCTGG	20	TCATCCTGGCGATCTACTTCCTCTGGCAGAACCTAGGTC
			ACTTCCT		GCAA		AGTCGCTTTCAT		CCTCTGTCCTGGCTGGAGTCGCTTTCATGGTCTTGCTGA
									TTCCACTCAACGG

ABCC4	NM_005845	21	AGCGCCTGGAATCTA	22	AGAGCCCCTGGAGAGA	23	CGGAGTCCAGTGTT	24	AGCGCCTGGAATCTACAACTCGGAGTCCAGTGTTTTCCC
			CAACT		AGAT		TTCCCACTTA		ACTTATCATCTTCTCTCCAGGGGCTCT

ABCC8	NM_000351	25	CGTCTGTCACTGTGG	26	TGATCCGGTTTAGCAG	27	AGTCTCTTGGCCAC	28	CGTCTGTCACTGTGGAGTGGACAGGGCTGAAGGTGGCCA
			AGTGG		GC		CTTCAGCCCT		AGAGACTGCACCGCAGCCTGCTAAACCGGATCA

ABCG2	NM_004827	29	GGTCTCAACGGCATC	30	CTTGGATCTTTCCTTG	31	ACGAAGATTTGCCT	32	GGTCTCAACGCCATCCTGGGACCCACAGGTGGAGGCAAA
			CTG		CAGC		CCACCTGTGG		TCTTCGTTATTAGATGTCTTAGCTGCAAGGAAAG

ABHD2	NM_007011	33	GTAGTGGGTCTGCAT	34	TGAGGGTTGGCACTCA	35	CAGGTGGCTCCTTT	36	GTAGTGGGTCTGCATGGATGTTTCAGGGATCAAAGGAGC
			GGATGT		GG		GATCCCTGA		CACCTGGGCGCCTGAGTGCCAACCCTCA

ACE	NM_000789	37	CCGCTGTACGAGGAT	38	CCGTGTCTGTGAAGCC	39	TGCCCTCAGCAATG	40	CCGCTGTACGAGGATTTCACTGCCCTCAGCAATGAAGCC
			TTCA		GT		AAGCCTACAA		TACAAGCAGGACGGCTTCACAGACACGG

ACOX2	NM_003500	41	ATGGAGGTGCCCAGA	42	ACTCCGGGTAACTGTG	43	TGCTCTCAACTTTC	44	ATGGAGGTGCCCAGAACACTGCACTCCGCAGGAAAGTTG
			ACAC		GATG		CTGCGGAGTG		AGAGCATCATCCACAGTTACCCGGAGT

ACTR2	NM_005722	45	ATCCGCATTGAAGAC	46	ATCCGCTAGAACTGCA	47	CCCGCAGAAAGCAC	48	ATCCGCATTGAAGACCCACCCCGCAGAAAGCACATGGTA
			CCA		CCAC		ATGGTATTCC		TTCCTGGGTGGTGCAGTTCTAGCGGAT

ADAM15	NM_003815	49	GGCGGGATGTGGT	50	ATTTCTGGGCCTCCG	51	TCAGCCACAATCAC	52	GGCGGGATGTGGTAACAGAGACCAAGACTGTGGAGT
							CAACTC

ADAMTS1	NM_006988	53	GGACAGGTGCAAGCT	54	ATCTACAACCTTGGGC	55	CAAGCCAAAGGCAT	56	GGACAGGTGCAAGCTCATCTGCCAAGCCAAAGGCATTGG
			CATCTG		TGCAA		TGGCTACTTCTTCG		CTACTTCTTCGTTTTGCAGCCCAAGGTTGTAGAT

ADH5	NM_000671	57	ATGCTGTCATCATT	58	CTGCTTCCTTTCCCTT	59	TGTCTGCCCATTAT	60	ATGCTGTCATCATTGTCACGGTTTGTCTGCCCATTAT
							CTTCAT

AFAP1	NM_198595	61	GATGTCCATCCTT	62	CAACCCTGATGCCTG	63	CCTCCAGTGCTGTG	64	GATGTCCATCCTTGAAACAGCCTCTTCTGGGAACACA
							TTCCCA

AGTR1	NM_000685	65	AGCATTGATCGAT	66	CTACAAGCATTGTGC	67	ATTGTTCACCCAAT	68	AGCATTGATCGATACCTGGCTATTGTTCACCCAATGA
							GAAGTC

AGTR2	NM_000686	69	ACTGGCATAGGAA	70	ATTGACTGGGTCTCTT	71	CCACCCAGACCCCA	72	ACTGGCATAGGAAATGGTATCCAGAATGGAATTTTG
							TGTAGC

AIG1	NM_016108	73	CGACGGTTCTGCC	74	TGCTCCTGCTGGGAT	75	AATCGAGATGAGGA	76	CGACGGTTCTGCCCTTTATATTAATCGAGATGAGGAC
							CATCGC

AKAP1	NM_003488	77	TGTGGTTGGAGAT	78	GTCTACCCACTGGGC	79	CTCCACCAGGGACC	80	TGTGGTTGGAGATGAAGTGGTGTTGATAAACCGGTC
							GGTTTA

AKR1C1	BC040210	81	GTGTGTGAAGCTG	82	CTCTGCAGGCGCATA	83	CCAAATCCCAGGAC	84	GTGTGTGAAGCTGAATGATGGTCACTTCATGCCTGTG
							AGGCAT

AKR1C3	NM_003739	85	GCTTTGCCTGATGTC	86	GTCCAGTCACCGGCAT	87	TGCGTCACCATCCA	88	GCTTTGCCTGATGTCTACCAGAAGCCCTGTGTGTGGATG
			TACCAGAA		AGAGA		CACACAGGG		GTGACGCAGAGGACGTCTCTATGCCGGTGACTGG

AKT1	NM_005163	89	CGCTTCTATGGCG	90	TCCCGGTACACCACG	91	CAGCCCTGGACTAC	92	CGCTTCTATGGCGCTGAGATTGTGTCAGCCCTGGACT
							CTGCAC

AKT2	NM_001626	93	TCCTGCCACCCTTC	94	GGCGGTAAATTCATC	95	CAGGTCACGTCCGA	96	TCCTGCCACCCTTCAAACCTCAGGTCACGTCCGAGGT
							GGTCGA

AKT3	NM_005465	97	TTGTCTCTGCCTTGG	98	CCAGCATTAGATTCTC	99	TCACGGTACACAAT	100	TTGTCTCTGCCTTGGACTATCTACATTCCGGAAAGATTG
			ACTATCTACA		CAACTTGA		CTTTCCGGA		TGTACCGTGATCTCAAGTTGGAGAATCTAATGCTG

ALCAM	NM_001627	101	GAGGAATATGGAA	102	GTGGCGGAGATCAAG	103	CCAGTTCCTGCCGT	104	GAGGAATATGGAATCCAAGGGGGCCAGTTCCTGCCG
							CTGCTC

ALDH18A1	NM_002860	105	GATGCAGCTGGAACC	106	CTCCAGCTCAGTGGGG	107	CCTGAAACTTGCAT	108	GATGCAGCTGGAACCCAAGCTGCAGCAGGAGATGCAAGT
			CAA		AA		CTCCTGCTGC		TTCAGGATGTTCCCCACTGAGCTGGAG

ALDH1A	NM_170696	109	CACGTCTGTCCCT	110	GACCGTGGCTCAACT	111	TCTCTGTAGGGCCC	112	CACGTCTGTCCCTCTCTGCTTTCTCTGTAGGGCCCAG
							AGCTCT

ALKBH3	NM_139178	113	TCGCTTAGTCTGC	114	TCTGAGCCCCAGTTTT	115	TAAACAGGGCAGTC	116	TCGCTTAGTCTGCACCTCAACCGTGCGGAAAGTGACT
							ACTTTC

ALOX12	NM_000697	117	AGTTCCTCAATGG	118	AGCACTAGCCTGGAG	119	CATGCTGTTGAGAC	120	AGTTCCTCAATGGTGCCAACCCCATGCTGTTGAGACG
							GCTCGA

ALOX5	NM_000698	121	GAGCTGCAGGACT	122	GAAGCCTGAGGACTT	123	CCGCATGCCGTACA	124	GAGCTGCAGGACTTCGTGAACGATGTCTACGTGTAC
							CGTAGA

AMACR	NM_203382	125	GTCTCTGGGCTGTCA	126	TGGGTATAAGATCCAG	127	TCCATGTGTTTGAT	128	GTCTCTGGGCTGTCAGCTTTCCTTTCTCCATGTGTTTGA
			GCTTT		AACTTGC		TTCTCCTCAGGC		TTTCTCCTCAGGCTGGTAGCAAGTTCTGGATCTTA

AMPD3	NM_000480	129	TGGTTCATCCAGCAC	130	CATAAATCCGGGGCAC	131	TACTCTCCCAACAT	132	TGGTTCATCCAGCACAAGGTCTACTCTCCCAACATGCGC
			AAGG		CT		GCGCTGGATC		TGGATCATCCAGGTGCCCCGGATTTATG

ANGPT2	NM_001147	133	CCGTGAAAGCTGC	134	TTGCAGTGGGAAGAA	135	AAGCTGACACAGCC	136	CCGTGAAAGCTGCTCTGTAAAAGCTGACACAGCCCT
							CTCCCA

ANLN	NM_018685	137	TGAAAGTCCAAAA	138	CAGAACCAAGGCTAT	139	CCAAAGAACTCGTG	140	TGAAAGTCCAAAACCAGGAAAATTCCAAAGAACTCG
							TCCCTC

ANPEP	NM_001150	141	CCACCTTGGACCAAA	142	TCTCAGCGTCACCTGG	143	CTCCCCAACACGCT	144	CCACCTTGGACCAAAGTAAAGCGTGGAATCTTACCGCCT
			GTAAAGC		TAGGA		GAAACCCG		CCCCAACACGCTGAAACCCGATTCCTACCGGG

ANXA2	NM_004039	145	CAAGACACTAAGGGC	146	CGTGTCGGGCTTCAGT	147	CCACCACACAGGTA	148	CAAGACACTAAGGGCGACTACCAGAAAGCGCTGCTGTAC
			GACTACCA		CAT		CAGCAGCGCT		CTGTGTGGTGGAGATGACTGAAGCCCGACACG

APC	NM_000038	149	GGACAGCAGGAAT	150	ACCCACTCGATTTGTT	151	CATTGGCTCCCCGT	152	GGACAGCAGGAATGTGTTTCTCCATACAGGTCACGG
							GACCTG

APEX1	NM_001641	153	GATGAAGCCTTTC	154	AGGTCTCCACACAGC	155	CTTTCGGGAAGCCA	156	GATGAAGCCTTTCGCAAGTTCCTGAAGGGCCTGGCTT
							GGCCCT

APOC1	NM_001645	157	CCAGCCTGATAAA	158	CACTCTGAATCCTTGC	159	AGGACAGGACCTCC	160	CCAGCCTGATAAAGGTCCTGCGGGCAGGACAGGACC
							CAACCA

APOE	NM_000041	161	GCCTCAAGAGCTGGT	162	CCTGCACCTTCTCCAC	163	ACTGGCGCTGCATG	164	GCCTCAAGAGCTGGTTCGAGCCCCTGGTGGAAGACATGC
			TCG		CA		TCTTCCAC		AGCGCCAGTGGGCCGGGCTGGTGGAGAAGGTGC

APRT	NM_000485	165	GAGGTCCTGGAGT	166	AGGTGCCAGCTTCTC	167	CCTTAAGCGAGGTC	168	GAGGTCCTGGAGTGCGTGAGCCTGGTGGAGCTGACC
							AGCTCC

AQP2	NM_000486	169	GTGTGGGTGCCAG	170	CCCTTCAGCCCTCTCA	171	CTCCTTCCCTTCCC	172	GTGTGGGTGCCAGTCCTCCTCAGGAGAAGGGGAAGG
							CTTCTCC

AR	NM_000044	173	CGACTTCACCGCA	174	TGACACAAGTGGGAC	175	ACCATGCCGCCAGG	176	CAGCTTCACCGCACCTGATGTGTGGTACCCTGGCGG
							GTACCA

ARF1	NM_001658	177	CAGTAGAGATCCC	178	ACAAGCACATGGCTA	179	CTTGTCCTTGGGTC	180	CAGTAGAGATCCCCGCAACTCGCTTGTCCTTGGGTCA
							ACCCTG

ARHGAP29	NM_004815	181	CACGGTCTCGTGGTG	182	CAGTTGCTTGCCCAGG	183	ATGCCAGACCCAGA	184	CACGGTCTCGTGGTGAAGTCAATGCCAGACCCAGACAAA
			AAGT		AC		CAAAGCATCA		GCATCAGCTTGTCCTGGGCAAGCAACTG

ARHGD1	NM_001175	185	TGGTCCCTAGAAC	186	TGATGGAGGATCAGA	187	TAAAACCGGGCTTT	188	TGGTCCCTAGAACAAGAGGCTTAAAACCGGGCTTTC
							CACCCA

ASAP2	NM_003887	189	CGGCCCATCAGCT	190	CTCTGGCCAAAGATA	191	CTGGGCTCCAACCA	192	CGGCCCATCAGCTTCTACCAGCTGGGCTCCAACCAG
							GCTTCA

ASPN	NM_017680	193	TGGACTAATCTGT	194	AAACACCCTTCAACA	195	AGTATCACCCAGGG	196	TGGACTAATCTGTGGGAGCAGTTTATTCCAGTATCAC
							TGCAGC

ATM	NM_000051	197	TGCTTTCTACACAT	198	GTTGTGGATCGGCTC	199	CCAGCTGTCTTCGA	200	TGCTTTCTACACATGTTCAGGGATTTTTCACCAGCTG
							CACTTC

ATP5E	NM_006886	201	CCGCTTTCGCTAC	202	TGGGAGTATCGGATG	203	TCCAGCCTGTCTCC	204	CCGCTTTCGCTACAGCATGGTGGCCTACTGGAGACA
							AGTAGG

ATP5J	NM_0010037	205	GTCGACCGACTGAAA	206	CTCTACTTCCGGCCC	207	CTACCCGCCATCGC	208	GTCGACCGACTGAAACGGCGGCCCATAATGCATTGCGAT
	03		CGG		TGG		AATGCATTAT		GGCGGGTAGGCGTGTGGGGGCGGAGCCAGGGCC

ATXN1	NM_000332	209	GATCGACTCCAGC	210	GAACTGTATCACGGC	211	CGGGCTATGGCTGT	212	GATCGACTCCAGCACCGTAGAGGATTGAAGACAG
							CTTCAA

AURKA	NM_003600	213	CATCTTCCAGGAG	214	TCCGACCTTCAATCAT	215	CTCTGTGGCACCCT	216	CATCTTCCAGGAGGACCACTCTCTGTGGCACCCTGGA
							GGACTA

AURKB	NM_004217	217	AGCTGCAGAAGAG	218	GCATCTGCCAACTCC	219	TGACGAGCAGCGAA	220	AGCTGCAGAAGAGCTGCACATTTGACGAGCAGCGAA
							CAGCC

AXIN2	NM_004655	221	GGCTATGTCTTTG	222	ATCCGTCAGCGCATC	223	ACCAGCGCCAACGA	224	GGCTATGTCTTTGCACCAGCCACCAGCGCCAACGAC
							CAGTG

AZGP1	NM_001185	225	GAGGCCAGCTAGG	226	CAGGAAGGGCAGCTA	227	TCTGAGATCCCACA	228	GAGGCCAGCTAGGAAGCAAGGGTTGGAGGCAATGTG
							TTGCCT

BAD	NM_032989	229	GGGTCAGGGGCCT	230	CTGCTCACTCGGCTC	231	TGGGCCCAGAGCAT	232	GGGTCAGGGGCCTCGAGATCGGGCTTGGGCCCAGAG
							GTTCCA

BAG5	NM_001015049	233	ACTCCTGCAATGAAC	234	ACAAACAGCTCCCCAC	235	ACACCGGATTTAGC	236	ACTCCTGCAATGAACCCTGTTGACACCGGATTTAGCTCT
			CCTGT		GA		TCTTGTCGGC		TGTCGGCCTTCGTGGGGAGCTGTTTGT

BAK1	NM_001188	237	CCATTCCCACCATT	238	GGGAACATAGACCCA	239	ACACCCCAGACGTC	240	CCATTCCCACCATTCTACCTGAGGCCAGGACGTCTGG
							CTGGCC

BAX	NM_004324	241	CCGCCGTGGACAC	242	TTGCCGTCAGAAAAC	243	TGCCACTCGGAAAA	244	CCGCCGTGGACACAGACTCCCCCCGAGAGGTCTTTTT
							AGACCT

BBC3	NM_014417	245	CCTGGAGGGTCCTGT	246	CTAATTGGGCTCCATC	247	CATCATGGGACTCC	248	CCTGGAGGGTCCTGTACAATCTCATCATGGGACTCCTGC
			ACAAT		TCG		TGCCCTTACC		CCTTACCCAGGGGCCACAGAGCCCCCGAGATGGA

BCL2	NM_000633	249	CAGATGGACCTAGTA	250	CCTATGATTTAAGGGC	251	TTCCACGCCGAAGG	252	CAGATGGACCTAGTACCCACTGAGATTTCCACGCCGAAG
			CCCACTGAGA		ATTTTTCC		ACAGCGAT		GACAGCGATGGGAAAAATGCCCTTAAATCATAG

BDKRB1	NM_000710	253	GTGGCAGAAATCT	254	GAAGGGCAAGCCCAA	255	ACCTGGCAGCCTCT	256	GTGGCAGAAATCTACCTGGCCAACCTGGCAGCCTCT
							GATCTG

BGN	NM_001711	257	GAGCTCCGCAAGG	258	CTTGTTGTTCACCAGG	259	CAAGGGTCTCCAGC	260	GAGCTCCGCAAGGATGACTTCAAGGGTCTCCAGCAC
							ACCTCT

BIK	NM_001197	261	ATTCCTATGGCTCTG	262	GGCAGGAGTGAATGGC	263	CCGGTTAACTGTGG	264	ATTCCTATGGCTCTGCAATTGTCACCGGTTAACTGTGGC
			CAATTGTC		TCTTC		CCTGTGCCC		CTGTGCCCAGGAAGAGCCATTCACTCCTGCC

BIN1	NM_004305	265	CCTGCAAAAGGGAAC	266	CGTGGTTGACTCTGAT	267	CTTCGCCTCCAGAT	268	CCTGCAAAAGGGAACAAGAGCCCTTCGCCTCCAGATGGC
			AAGAG		CTCG		GGCTCCC		TCCCCTGCCGCCACCCCCGAGATCAGAGTCAAC

BIRC5	NM_001012271	269	TTCAGGTGGATGAGG	270	CACACAGCAGTGGCAA	271	TCTGCCAGACGCTT	272	TTCAGGTGGATGAGGAGACAGAATAGAGTGATAGGAAGC
			AGACA		AAG		CCTATCACTCTATT		GTCTGGCAGATACTCCTTTTGCCACTGCTGTGTG
							C

BMP6	NM_001718	273	GTGCAGACCTTGG	274	CTTAGTTGGCGCACA	275	TGAACCCCGAGTAT	276	GTGCAGACCTTGGTTCACCTTATGAACCCCGAGTATG
							GTCCCC

BMPR1B	NM_001203	277	ACCACTTTGGCCA	278	GCGGTGTTTGTACCC	279	ATTCACATTACCAT	280	ACCACTTTGGCCATCCCTGCATTTGGGGCCGTCTATGG
							AGCGGC

BRCA1	NM_007294	281	TCAGGGGGCTAGA	282	CCATTCCAGTTGATCT	283	CTATGGGCCCTTCA	284	TCAGGGGGCTAGAAATCTGTTGCTATGGGCCCTTCAC
							CCAACA

BRCA2	NM_000059	285	AGTTCGTGCTTTG	286	AAGGTAAGCTGGGTC	287	CATTCTTCACTGCT	288	AGTTCGTGCTTTGCAAGATGGTGCAGAGCTTTATGAA
							TCATAA

BTG1	NM_001731	289	GAGGTCCGAGCGA	290	AGTTATTTTCGAGAC	291	CGCTCGTCTCTTCC	292	GAGGTCCGAGCGATGTGACCAGGCCGCCATCGCTCG
							TCTCTC

BTG3	NM_006806	293	CCATATCGCCCAA	294	CCAGTGATTCCGGTC	295	CATGGGTACCTCCT	296	CCATATCGCCCAATTCCAGTGACATGGGTACCTCCTC
							CCTGGA

BTRC	NM_033637	297	GTTGGGACACAGT	298	TGAAGCAGTCAGTTG	299	CAGTCGGCCCAGGA	300	GTTGGGACACAGTTGGTCTGCAGTCGGCCCAGGACG
							CGGTCT

BUB1	NM_004336	301	CCGAGGTTAATCC	302	AAGACATGGCGCTCT	303	TGCTGGGAGCCTAC	304	CCGAGGTTAATCCAGCACGTATGGGGCCAAGTGTAG
							ACTTGG

C7	NM_000587	305	ATGTCTGAGTGTG	306	AGGCCTTATGCTGGT	307	ATGCTCTGCCCTCT	308	ATGTCTGAGTGTGAGGCGGGCGCTCTGAGATGCAGA
							GCATCT

CACNA1D	NM_000720	309	AGGACCCAGCTCCAT	310	CCTACATTCCGTGCC	311	CAGTACACTGGCGT	312	AGGACCCAGCTCCATGTGCGTTCTCAGGGAATGGACGCC
			GTG		ATTG		CCATTCCCTG		AGTGTACTGCCAATGGCACGGAATGTAGG
CADM1	NM_014333	313	CCACCACCATCCT	314	GATCCACTGCCCTGA	315	TCTTCACCTGCTCG	316	CCACCACCATCCTTACCATCATCACAGATTCCCGAGC
							GGAATC

CADPS	NM_003716	317	CAGCAAGGAGACT	318	GGTCCTCTTCTCCACG	319	CTCCTGGATGGCCA	320	CAGCAAGGAGACTGTGCTGAGCTCCTGGATGGCCAA
							AATTTG

CASP1	NM_001223	321	AACTGGAGCTGAG	322	CATCTACGCTGTACC	323	TCACAGGCATGACA	324	AACTGGAGCTGAGGTTGACATCACAGGCATGACAAT
							ATGCTG

CASP3	NM_032991	325	TGAGCCTGAGCAG	326	CCTTCCTGCGTGGTCC	327	TCAGCCTGTTCCAT	328	TGAGCCTGAGCAGAGACATGACTCAGCCTGTTCCAT
							GAAGGC

CASP7	NM_033338	329	GCAGCGCCGAGAC	330	AGTCTCTCTCCGTCGC	331	CTTTCGCTAAAGGG	332	GCAGCGCCGAGACTTTAGTTTCGCTTTCGCTAAAGG
							GCCCCA

CAV1	NM_001753	333	GTGGCTCAACATT	334	CAATGGCCTCCATTTT	335	ATTTCAGCTGATCA	336	GTGGCTCAACATTGTGTTCCCATTTCAGCTGATCAGT
							GTGGGC

CAV2	NM_198212	337	CTTCCCTGGGACG	338	CTCCTGGTCACCCTTC	339	CCCGTACTGTCATG	340	CTTCCCTGGGACGACTTGCCAGCTCTGAGGCATGAC
							CCTCAG

CCL2	NM_002982	341	CGCTCAGCCAGATGC	342	GCACTGAGATCTTCCT	343	TGCCCCAGTCACCT	344	CGCTCAGCCAGATGCAATCAATGCCCCAGTCACCTGCTG
			AATC		ATTGGTGAA		GCTGTTA		TTATAACTTCACCAATAGGAAGATCTCAGTGC

CCL5	NM_002985	345	AGGTTCTGAGCTC	346	ATGCTGACTTCCTTCC	347	ACAGAGCCCTGGCA	348	AGGTTCTGAGCTCTGGCTTTGCCTTGGCTTTGCCAGG
							AAGCC

CCNB1	NM_031996	349	TTCAGGTTGTTGCAG	350	CATCTTCTTGGGCACA	351	TGTCTCCATTATGA	352	TTCAGGTTGTTGCAGGAGACCATGTACATGACTGTCTCC
			GAGAC		CAAT		TCGGTTCATGCA		ATTATTGATCGGTTCATGCAGAATAATTGTGTGCC
CCND1	NM_001758	353	GCATGTTCGTGGC	354	CGGTGTAGATGCACA	355	AAGGAGACCATCCC	356	GCATGTTCGTGGCCTCTAAGATGAAGGAGACCATCC
							CCTGAC

CCNE2	NM_057749	357	ATGCTGTGGCTCCTT	358	ACCCAAATTGTGATAT	359	TACCAAGCAACCTA	360	ATGCTGTGGCTCCTTCCTAACTGGGGCTTTCTTGACATGT
			CCTAACT		ACAAAAAGGTT		CATGTCAAGAAAGC		AGGTTGCTTGGTAATAACCTTTTTGTATATCACA
							CC

CCNH	NM_001239	361	GAGATCTTCGGTG	362	CTGCAGACGAGAACC	363	CATCAGCGTCCTGG	364	GAGATCTTCGGTGGGGGTACGGGTGTTTTACGCCAG
							CGTAAA

CCR1	NM_001295	365	TCCAAGACCCAAT	366	TCGTAGGCTTTCGTG	367	ACTCACCACACCTG	368	TCCAAGACCCAATGGGAATTCACTCACCACACCTGC
							CAGCCT

CD164	NM_006016	369	CAACCTGTGCGAA	370	ACACCCAAGACCAGGC	371	CCTCCAATGAAACT	372	CAACCTGTGCGAAAGTCTACCTTTGATGCAGCCAGTT
							GGCTGC

CD1A	NM_001763	373	GGAGTGGAAGGAACT	374	TCATGGGCGTATCTAG	375	CGCACCATTCGGTC	376	GGAGTGGAAGGAACTGGAAACATTATTCCGTATACGCAC
			GGAAA		AAT		ATTTGAGG		CATTCGGTCATTTGAGGGAATTCGTAGATACGCC
CD276	NM_001024736	377	CCAAAGGATGCGATA	378	GGATGACTTGGGAATC	379	CCACTGTGCAGCCT	380	CCAAAGGATGCGATACACAGACCACTGTGCAGCCTTATT
			CACAG		ATGTC		TATTTCTCCAATG		TCTCCAATGGACATGATTCCCAAGTCATCC
CD44	NM_000610	381	GGCACCACTGCTT	382	GATGCTCATGGTGAA	383	ACTGGAACCCAGAA	384	GGCACCACTGCTTATGAAGGAAACTGGAACCCAGAA
							GCACA

CD68	NM_001251	385	TGGTTCCCAGCCC	386	CTCCTCCACCCTGGGT	387	CTCCAAGCCCAGAT	388	TGGTTCCCAGCCCTGTGTCCACCTCCAAGCCCAGATT
							TCAGAT

CD82	NM_002231	389	GTGCAGGCTCAGGTG	390	GACCTCAGGGCGATTC	391	TCAGCTTCTACAAC	392	GTGCAGGCTCAGGTGAAGTGCTGCGGCTGGGTCAGCTTC
			AAGTG		ATGA		TGGACAGACAACGC		TACAACTGGACAGACAACGCTGAGCTCATGAAT
							TG

CDC20	NM_001255	393	TGGATTGGAGTTC	394	GCTTGCACTCCACAG	395	ACTGGCCGTGGCAC	396	TGGATTGGAGTTCTGGGAATGTACTGGCCGTGGCAC
							TGGACA

CDC25B	NM_021873	397	GCTGCAGGACCAG	398	TAGGGCAGCTGGCTT	399	CTGCTACCTCCCTT	400	GCTGCAGGACCAGTGAGGGGCCTGCGCCAGTCCTGC
							GCCTTT

CDC6	NM_001254	401	GCAACACTCCCCA	402	TGAGGGGACCATTC	403	TTGTTCTCCACCAA	404	GCAACACTCCCCATTTACCTCCTTGTTCTCCACCAAA
							AGCAAG

CDH1	NM_004360	405	TGAGTGTCCCCCGGT	406	CAGCCGCTTTCAGAT	407	TGCCAATCCCGATG	408	TGAGTGTCCCCCGGTATCTTCCCCGCCCTGCCAATCCCG
			ATCTTC		TTTCAT		AAATTGGAAATTT		ATGAAATTGGAAATTTTATTGATGAAAATCTGAAA

CDH10	NM_006727	409	TGTGGTGCAAGTC	410	TGTAAATGACTCTGG	411	ATGCCGATGACCCT	412	TGTGGTGCAAGTCACAGCTACAGATGCCGATGACCC
							TCATAT

CDH11	NM_001797	413	GTCGGCAGAAGCA	414	CTACTCATGGGCGGG	415	CCTTCTGCCCATAG	416	GTCGGCAGAAGCAGGACTTGTACCTTCTGCCCATAG
							TGATCA

CDH19	NM_021153	417	AGTACCATAATGC	418	AGACTGCCTGTATAG	419	ACTCGGAAAACCAC	420	AGTACCATAATGCGGGAACGCAAGACTCGGAAAACC
							AAGCG

CDH5	NM_001795	421	ACAGGAGACGTGT	422	CAGCAGTGAGGTGGT	423	TATTCTCCCGGTCC	424	ACAGGAGACGTGTTCGCCATTGAGAGGCTGGACCGG
							AGCCTC

CDH7	NM_033646	425	GTTTGACATGGCT	426	AGTCACATCCCTCCG	427	ACCTCAACGTCATC	428	GTTTGACATGGCTGCACTGAGAAACCTCAACGTCATC
							CGAGAC

CDK14	NM_012395	429	GCAAGGTAAATGG	430	GATAGCTGTGAAAGG	431	CTTCCTGCAGCCTG	432	GCAAGGTAAATGGGAAGTTGGTAGCTCTGAAGGTGA
							ATCACC

CDK2	NM_001798	433	AATGCTGCACTACGA	434	TTGGTCACATCCTGG	435	CCTTGGCCGAAATC	436	AATGCTGCACTACGACCCTAACAAGCGGATTTCGGCCAA
			CCCTA		AAGAA		CGCTTGT		GGCAGCCCTGGCTCACCTTTCTTCCAGGATGTG

CDK3	NM_001258	437	CCAGGAAGGGACT	438	GTTGCATGAGCAGGT	439	CTCTGGCTCCAGAT	440	CCAGGAAGGGACTGGAAGAGATTGTGCCCAATCTGG
							TGGGCA

CDK7	NM_001799	441	GTCTCGGGCAAAG	442	CTCTGGCCTTGTAAA	443	CCTCCCCAAGGAAG	444	GTCTCGGGCAAAGCGTTATGAGAAGCTGGACTTCCT
							TCCAGC

CDKN1A	NM_000389	445	TGGAGACTCTCAG	446	GGCGTTTGGAGTGGT	447	CGGCGGCAGACCAG	448	TGGAGACTCTCAGGGTCGAAAACGGCGGCAGACCAG
							CATGA

CDKN1C	NM_000076	449	CGGCGATCAAGAA	450	CAGGCGCTGATCTCT	451	CGGGCCTCTGATCT	452	CGGCGATCAAGAAGCTGTCCGGGCCTCTGATCTCCG
							CCGATT

CDKN2B	NM_004936	453	GACGCTGCAGAGC	454	GCGGGAATCTCTCCT	455	CACAGGATGCTGGC	456	GACGCTGCAGAGCACCTTTGCACAGGATGCTGGCCT
							CTTTGC

CDKN2C	NM_001262	457	GAGCACTGGGCAA	458	CAAAGGCGAACGGGA	459	CCTGTAACTTGAGG	460	GAGCACTGGGCAATCGTTACGACCTGTAACTTGAGG
							GCCACC

CDKN3	NM_005192	461	TGGATCTCTACC	462	ATGTCAGGAGTCCCT	463	ATCACCCATCATCA	464	TGGATCTCTACCAGCAATGTGGAATTATCACCCATCA
							TCCAAT

CDS2	NM_003818	465	GGGCTTCTTTGCT	466	ACAGGGCAGACAAAG	467	CCCGGACATCACAT	468	GGGCTTCTTTGCTACTGTGGTGTTTGGCCTTCTGCTG
							AGGACA

CENPF	NM_016343	469	CTCCCGTCAACAG	470	GGGTGAGTCTGGCCT	471	ACACTGGACCAGGA	472	CTCCCGTCAACAGCGTTCTTTCCAAACACTGGACCAG
							GTGCAT

CHAF1A	NM_005483	473	GAACTCAGTGTAT	474	GCTCTGTAGCACCTG	475	TGCACGTACCAGCA	476	GAACTCAGTGTATGAGAAGCGGCCTGACTTCAGGAT
							CATCCT

CHN1	NM_001822	477	TTACGACGCTCGT	478	TCTCCCTGATGCACAT	479	CCACCATTGGCCGC	480	TTACGACGCTCGTGAAAGCACATACCACTAAGCGGC
							TTAGTG

CHRAC1	NM_017444	481	TCTCGCTGCCTCTA	482	CCTGGTTGATGCTGG	483	ATCCGGGTCATCAT	484	TCTCGCTGCCTCTATCCCGCATCCGGGTCATCATGAA
							GAAGAG

CKS2	NM_001827	485	GGCTGGACGTGGT	486	CGCTGCAGAAAATGA	487	CTGCGCCCGCTCTT	488	GGCTGGACGTGGTTTTGTCTGCTGCGCCCGCTCTTCG
							CGCG

CLDN3	NM_001306	489	ACCAACTGCGTGC	490	GGCGAGAAGGAACAG	491	CAAGGCCAAGATCA	492	ACCAACTGCGTGCAGGACGACACGGCCAAGGCCAAG
							CCATCG

CLTC	NM_004859	493	ACCGTATGGACAG	494	TGACTACAGGATCAG	495	TCTCACATGCTGTA	496	ACCGTATGGACAGCCACAGCCTGGCTTTGGGTACAG
							CCCAAA

COL11A	NM_001854	497	GCCCAAGAGGGGA	498	GGACCTGGGTCTCCA	499	CTGCTCGACCTTTG	500	GCCCAAGAGGGGAAGATGGCCCTGAAGGACCCAAAG
							GGTCCT

COL1A1	NM_000088	501	GTGGCCATCCAGC	502	CAGTGGTAGGTGATG	503	TCCTGCGCCTGATG	504	GTGGCCATCCAGCTGACCTTCCTGCGCCTGATGTCCA
							TCCACC

COL1A2	NM_000089	505	CAGCCAAGAACTGGT	506	AAACTGGCTGCCAGCA	507	TCTCCTAGCCAGAC	508	CAGCCAAGAACTGGTATAGGAGCTCCAAGGACAAGAAAC
			ATAGGAGCT		TTG		GTGTTTCTTGTCCT		ACGTCTGGCTAGGAGAAACTATCAATGCTGGCA
							TG

COL3A1	NM_000090	509	GGAGGTTCTGGAC	510	ACCAGGACTGCCACG	511	CTCCTGGTCCCCAA	512	GGAGGTTCTGGACCTGCTGGTCCTCCTGGTCCCCAAG
							GGTGTC

COL4A1	NM_001845	513	ACAAAGGCCTCCC	514	GAGTCCCAGGAAGAC	515	CTCCTTTGACACCA	516	ACAAAGGCCTCCCAGGATTGGATGGCATCCCTGGTG
							GGGATG

COL5A1	NM_000093	517	CTCCCTGGGAAAG	518	CTGGACCAGGAAGCC	519	CCAGGGAAACCACG	520	CTCCCTGGGAAAGATGGCCCTCCAGGATTACGTGGT
							TAATCC

COL5A2	NM_000393	521	GGTCGAGGAACCC	522	GCCTGGAGGTCCAAC	523	CCAGGAAATCCTGT	524	GGTCGAGGAACCCAAGGTCCGCCTGGTGCTACAGGA
							AGCACC

COL6A1	NM_001848	525	GGAGACCCTGGTG	526	TCTCCAGGGACACCA	527	CTTCTCTTCCCTGA	528	GGAGACCCTGGTGAAGCTGGCCCGCAGGGTGATCAG
							TCACCC

COL6A3	NM_004369	529	GAGAGCAAGCGAG	530	AACAGGGAACTGGCC	531	CCTCTTTGACGGCT	532	GAGAGCAAGCGAGACATTCTGTTCCTCTTTGACGGCT
							CAGCCA

COL8A1	NM_001850	533	TGGTGTTCCAGGG	534	CCCTGTAAACCCTGA	535	CCTAAGGGAGAGCC	536	TGGTGTTCCAGGGCTTCTCGGACCTAAGGGAGAGCC
							AGGAA

COL9A2	NM_001852	537	GGGAACCATCCAG	538	ATTCCGGGTGGACAG	539	ACACAGGAAATCCG	540	GGGAACCATCCAGGGTCTGGAAGGCAGTGCGGATTT
							CACTGC

CRISP3	NM_006061	541	TCCCTTATGAACA	542	AACCATTGGTGCATA	543	TGCCAGTTGCCCAG	544	TCCCTTATGAACAAGGAGCACCTTGTGCCAGTTGCCC
							ATAACT

CSF1	NM_000757	545	TGCAGCGGCTGATTG	546	CAACTGTTCCTGGTC	547	TCAGATGGAGACCT	548	TGCAGCGGCTGATTGACAGTCGATGGAGACCTCGTGCCA
			ACA		TACAAACTCA		CGTGCCAAATTACA		AATTACATTTGAGTTTGTAGACCAGGAACAGTT

CSK	NM_004383	549	CCTGAACATGAAG	550	CATCACGTCTCCGAA	551	TCCCGATGGTCTGC	552	CCTGAACATGAAGGAGCTGAAGCTGCTGCAGACCAT
							AGCAGC

CSRP1	NM_004078	553	ACCCAAGACCCTG	554	GCAGGGGTGGAGTGA	555	CCACCCTTCTCCAG	556	ACCCAAGACCCTGCCTCTTCCACTCCACCCTTCTCCA
							GGACCC

CTGF	NM_001901	557	GAGTTCAAGTGCCCT	558	AGTTGTAATGGCAGGC	559	AACATCATGTTCTT	560	GAGTTCAAGTGCCCTGACGGCGAGGTCATGAAGAAGAAC
			GACG		ACAG		CTTCATGACCTCGC		ATGATGTTCATCAAGACCTGTGCCTGCCATTACA

CTHRC1	NM_138455	561	TGGCTCACTTCGG	562	TCAGCTCCATTGAAT	563	CAACGCTGACAGCA	564	TGGCTCACTTCGGCTAAAATGCAGAAATGCATGCTGT
							TGCATT

CTNNA1	NM_001903	565	CGTTCCGATCCTCTA	566	AGGTCCCTGTTGGCCT	567	ATGCCTACAGCACC	568	CGTTCCGATCCTCTATACTGCATCCCAGGCATGCCTACA
			TACTGCAT		TATAGG		CTGATGTCGCA		GCACCCTGATGTCGCAGCCTATAAGGCCAACAGG

CTNNB1	NM_001904	569	GGCTCTTGTGCGTAC	570	TCAGATGACGAAGAGC	571	AGGCTCAGTGATGT	572	GGCTCTTGTGCGTACTGTCCTTCGGGCTGGTGACAGGGA
			TGTCCTT		ACAGATG		CTTCCCTGTCACCA		AGACATCACTGAGCCTGCCATCTGTGCTCTTCGTC
							G

CTNND1	NM_001331	573	CGGAAACTTCGGG	574	CTGAATCCTTCTGCCC	575	TTGATGCCCTCATT	576	CGGAAACTTCGGGAATGTGATGGTTTAGTTGATGCC
							TTCATT

CTNND2	NM_001332	577	GCCCGTCCCTACA	578	CTCACACCCAGGAGT	579	CTATGAAACGAGCC	580	GCCCGTCCCTACAGTGAACTGAACTATGAAACGAGC
							ACTACC

CTSB	NM_001908	581	GGCCGAGATCTAC	582	GCAGGAAGTCCGAAT	583	CCCCGTGGAGGGAG	584	GGCCGAGATCTACAAAAACGGCCCCGTGGAGGGAGC
							CTTTCT

CTSD	BN_001909	585	GTACATGATCCCCTG	586	GGGACAGCTTGTAGCC	587	ACCCTGCCCGCGAT	588	GTACATGATCCCCTGTGAGAAGGTGTCCACCCTGCCCGC
			TGAGAAGGT		TTTGC		CACACTGA		GATCACACTGAAGCTGGGAGGCAAAGGCTACAAG

CTSK	NM_000396	589	AGGCTTCTCTTGG	590	CCACCTCTTCACTGGT	591	CCCCAGGTGGTTCA	592	AGGCTTCTCTTGGTGTCCATACATATGAACTGGCTAT
							TAGCCA

CTSL2	NM_001333	593	TGTCTCACTGAGC	594	ACCATTGCAGCCCTG	595	CTTGAGGACGCGAA	596	TGTCTCACTGAGCGAGCAGAATCTGGTGGACTGTTC
							CAGTCC

CTSS	NM_004079	597	TGACAACGGCTTT	598	TCCATGGCTTTGTAG	599	TGATAACAAGGGCA	600	TGACAACGGCTTTCCAGTACATCATTGATAACAAGG
							TCGACT

CUL1	NM_003592	601	ATGCCCTGGTAAT	602	GCGACCACAAGCCTT	603	CAGCCACAAAGCCA	604	ATGCCCTGGTAATGTCTGCATTCAACAATGACGCTGG
							GCGTCA

CXCL12	NM_000609	605	GAGCTACAGATGC	606	TTTGAGATGCTTGAC	607	TTCTTCGAAAGCCA	608	GAGCTACAGATGCCCATGCCGATTCTTCGAAAGCCA
							TGTTGC

CXCR4	NM_003467	609	TGACCGCTTCTAC	610	AGGATAAGGCCAACC	611	CTGAAACTGGAACA	612	TGACCGCTTCTACCCCAATGACTTGTGGGTGGTTGTG
							CAACCA

CXCR7	NM_020311	613	CGCCTCAGAACGATG	614	GTTGCATGGCCAGCTG	615	CTCAGAGCCAGGGA	616	CGCCTCAGAACGATGGATCTGCATCTTCGACTACTCAGA
			GAT		AT		ACTTCTCGGA		GCCAGGGAACTTCTCGGACATCAGCTGGCCAT

CYP3A5	NM_000777	617	TCATTGCCCAGTA	618	GACAGGCTTGCCTTT	619	TCCCGCCTCAAGTT	620	TCATTGCCCAGTATGGAGATGTATTGGTGAGAAACTT
							TCTCAC

CYR61	NM_001554	621	TGCTCATTCTTGAG	622	GTGGCTGCATTAGTG	623	CAGCACCCTTGGCA	624	TGCTCATTCTTGAGGAGCATTAAGGTATTTCGAAACT
							GTTTCG

DAG1	NM_004393	625	GTGACTGGGCTCA	626	ATCCCACTTGTGCTCC	627	CAAGTCAGAGTTTC	628	GTGACTGGGCTCATGCCTCCAAGTCAGAGTTTCCCTG
							CCTGGT

DAP	NM_004394	629	CCAGCCTTTCTGG	630	GACCAGGTCTGCCTC	631	CTCACCAGCTGGCA	632	CCAGCCTTTCTGGTGCTGTTCTCCAGTTCACGTCTGC
							GACGTG

DAPK1	NM_004938	633	CGCTGACATCATG	634	TCTCTTTCAGCAACGA	635	TCATATCCAAACTC	636	CGCTGACATCATGAATGTTCCTCGACCGGCTGGAGG
							GCCTCC

DARC	NM_002036	637	GCCCTCATTAGTC	638	CAGACAGAAGGGCTG	639	TCAGCGCCTGTGCT	640	GCCCTCATTAGTCCTTGGCTCTTATCTTGGAAGCACA
							TCCAAG

DDIT4	NM_019058	641	CCTGGCGTCTGTC	642	CGAAGAGGAGGTGGA	643	CTAGCCTTTGGGAC	644	CCTGGCGTCTGTCCTCACCATGCCTAGCCTTTGGGAC
							CGCTTC

DDR2	NM_001014796	645	CTATTACCGGATCCA	646	CCCAGCAAGATACTCT	647	AGTGCTCCCTATCC	648	CTATTACCGGATCCAGGGCCGGGCAGTGCTCCCTATCCG
			GGGC		CCCA		GCTGGATGTC		CTGGATGTCTTGGGAGAGTATCTTGCTGGG

DES	NM_001927	649	ACTTCTCACTGGC	650	GCTCCACCTTCTCGTT	651	TGAACCAGGAGTTT	652	ACTTCTCACTGGCCGACGCGGTGAACCAGGAGTTTCT
							CTGACC

DHRS9	NM_005771	653	GGAGAAAGGTCTC	654	CAGTCAGTGGGAGCC	655	ATCAATAATGCTGG	656	GGAGAAAGGTCTCTGGGGTCTGATCAATAATGCTGG
							TGTTCC

DHX9	NM_001357	657	GTTCGAACCATCT	658	TCCAGTTGGATTGTG	659	CCAAGGAACCACAC	660	GTTCGAACCATCTCAGCGACAAAACCAAGTGGGTGT
							CCACTT

DIAPH1	NM_005219	661	CAAGCAGTCAAGG	662	AGTTTTGCTCGCCTCA	663	TTCTTCTGTCTCCC	664	CAAGCAGTCAAGGAGAACCAGAAGCGGCGGGAGAC
							GCCGCT

DICER1	NM_177438	665	TCCAATTCCAGCA	666	GGCAGTGAAGGCGAT	667	AGAAAAGCTGTTTG	668	TCCAATTCCAGCATCACTGTGGAGAAAAGCTGTTTGT
							TCTCCC

DIO2	NM_013989	669	CTCCTTTCACGAG	670	AGGAAGTCAGCCACT	671	ACTCTTCCACCAGT	672	CTCCTTTCACGAGCCAGCTGCCAGCCTTCCGCAAACT
							TTGCGG

DLC1	NM_006094	673	GATTCAGACGAGG	674	CACCTCTTGCTGTCCC	675	AAAGTCCATTTGCC	676	GATTCAGACGAGGATGAGCCTTGTGCCATCAGTGGC
							ACTGAT

DLGAP1	NM_004746	677	CTGCTGAGCCCAG	678	AGCCTGGAAGGAGTT	679	CGCAGACCACCCAT	680	CTGCTGAGCCCAGTGGAGCACCACCCCGCAGACCAC
							ACTACA

DLL4	NM_019074	681	CACGGAGGTATAA	682	AGAAGGAAGGTCCAG	683	CTACCTGGACATCC	684	CACGGAGGTATAAGGCAGGAGCCTACCTGGACATCC
							CTGCTC

DNM3	NM_015569	685	CTTTCCCACCCGG	686	AAGGACCTTCTGCAG	687	CATATCGCTGACCG	688	CTTTCCCACCCGGCTTACAGACATATCGCTGACCGAA
							AATGGG

DPP4	NM_001935	689	GTCCTGGGATCGG	690	GTACTCCCACCGGGA	691	CGGCTATTCCACAC	692	GTCCTGGGATCGGGAAGTGGCGTGTTCAAGTGTGGA
							TTGAAC

DPT	NM_001937	693	CACCTAGAAGCCT	694	CAGTAGCTCCCCAGG	695	TTCCTAGGAAGGCT	696	CACCTAGAAGCCTGCCCACGATTCCTAGGAAGGCTG
							GGCAGA

DUSP1	NM_004417	697	AGACATCAGCTCC	698	GACAAACACCCTTCC	699	CGAGGCCATTGACT	700	AGACATCAGCTCCTGGTTCAACGAGGCCATTGACTTC
							TCATAG

DUSP6	NM_001946	701	CATGCAGGGACTG	702	TGCTCCTACCCTATCA	703	TCTACCCTATGCGC	704	CATGCAGGGACTGGGATTCGAGGACTTCCAGGCGCA
							CTGGAA

DVL1	NM_004421	705	TCTGTCCCACCTG	706	TCAGACTGTTGCCGG	707	CTTGGAGCAGCCTG	708	TCTGTCCCACCTGCTGCTGCCCCTTGGAGCAGCCTGC
							CACCTT

DYNLL1	NM_001037494	709	GCCGCCTACCTCACA	710	GCCTGACTCCAGCTCT	711	ACCCACGTCAGTGA	712	GCCGCCTACCTCACAGACTTGTGAGCACTCACTGACGTG
			GAC		CCT		GTGCTCACAA		GGTAGCGCCCAGGGCCTGCGGGGCGCAGGAGAG

EBNA1BP2	NM_006824	713	TGCGGCGAGATGGAC	714	GTGACAAGGGATTCAT	715	CCCGCTCTCGGATT	716	TGCGGCGAGATGGACACTCCCCCGCTCTCGGATTCGGAG
			ACT		CGGATT		CGGAGTCG		TCGGAATCCGATGAATCCCTTGTCAC

ECE1	NM_001397	717	ACCTTGGGATCTG	718	GGACCAGGACCTCCA	719	TCCACTCTCGATAC	720	ACCTTGGGATCTGCCTCCAAGCTGGTGCAGGGTATC
							CCTGCA

EDN1	NM_001955	721	TGCCACCTGGACA	722	TGGACCTAGGGCTTC	723	CACTCCCGAGCACG	724	TGCCACCTGGACATCATTTGGGTCAACACTCCCGAGC
							TTGTTC

EDNRA	NM_001957	725	TTTCCTCAAATTTG	726	TTACACATCCAACCA	727	CCTTTGCCTCAGGG	728	TTTCCTCAAATTTGCCTCAAGATGGAAACCCTTTGCC
							CATCCT

EFNB2	NM_004093	729	TGACATTATCATCCC	730	GTAGTCCCCGCTGACC	731	CGGACAGCGTCTTC	732	TGACATTATCATCCCGCTAAGGACTGCGGACAGCGTCTT
			GCTAAGGA		TTCTC		TGCCCTCACT		CTGCCCTCACTACGAGAAGGTCAGCGGGGACTA

EGF	NM_001963	733	CTTTGCCTTGCTCTG	734	AAATACCTGACACCCT	735	AGAGTTTAACAGCC	736	CTTTGCCTTGCTCTGTCACAGTGAAGTCAGCCAGAGCAG
			TCACAGT		TATGACAAATT		CTGCTCTGGCTGAC		GGCTGTTAAACTCTGTGAAATTTGTCATAAGGGTG
							TT

EGR1	NM_001964	737	GTCCCCGCTGCAGAT	738	CTCCAGCTTAGGGTAG	739	CGGATCCTTTCCTC	740	GTCCCCGCTGCAGATCTCTGACCCGTTCGGATCCTTTCC
			CTCT		TTGTCCAT		ACTCGCCCA		TACTCGCCCACCATGGACAACTACCCTAAGCTGG

EGR3	NM_004430	741	CCATGTGGATGAATG	742	TGCCTGAGAAGAGGTG	743	ACCCAGTCTCACCT	744	CCATGTGGATGAATGAGGTGTCTCCTTTCCATACCCAGT
			AGGTG		AGGT		TCTCCCCACC		CTCACCTTCTCCCCACCCTACCTCACCTCTTCTCA

EIF2C2	NM_012154	745	GCACTGTGGGCAG	746	ATGTTTGGTGACTGG	747	CGGGTCACATTGCA	748	GCACTGTGGGCAGATGAAGAGGAAGTACCGCGTCTG
							GACACG

EIF2S3	NM_001415	749	CTGCCTCCCTGATT	750	GGTGGCAAGTGCCTG	751	TCTCGTGCTTCAGC	752	CTGCCTCCCTGATTCAAGTGATTCTCGTGCTTCAGCC
							CTCCCA

EIF3H	NM_003756	753	CTCATTGCAGGCCAG	754	GCCATGAAGAGCTTGC	755	CAGAACATCAAGGA	756	CTCATTGCAGGCCAGATAAACACTTACTGCCAGAACATC
			ATAAA		CTA		GTTCACTGCCCA		AAGGAGTTCACTGCCCAAAACTTAGGCAAGCTC

EIF4E	NM_001968	757	GATCTAAGATGGCGA	758	TTAGATTCCGTTTTCT	759	ACCACCCCTACTCC	760	GATCTAAGATGGCGACTGTCGAACCGGAAACCACCCCTA
			CTGTCGAA		CCTCTTCTG		TAATCCCCCGACT		CTCCTAATCCCCCGACTACAGAAGAGGAGAAAA

EIF5	NM_001969	761	GAATTGGTCTCCA	762	TCCAGGTATATGGCT	763	CCACTTGCACCCGA	764	GAATTGGTCTCCAGCTGCCTTTGATCAAGATTCGGGT
							ATCTTG

ELK4	NM_001973	765	GATGTGGAGAATG	766	AGTCATTGCGGCTAG	767	ATAAACCACCTCAG	768	GATGTGGAGAATGGAGGGAAAGATAAACCACCTCAG
							CCTGGT

ENPP2	NM_006209	769	CTCCTGCGCACTA	770	TCCCTGGATAATTGG	771	TAACTTCCTCTGGC	772	CTCCTGCGCACTAATACCTTCAGGCCAACCATGCCAG
							ATGGTT

ENY2	NM_020189	773	CCTCAAAGAGTTG	774	CCTCTTTACAGTGTGC	775	CTGATCCTTCCAGC	776	CCTCAAAGAGTTGCTGAGAGCTAAATTAATTGAATGT
							CACATT

EPHA2	NM_004431	777	CGCCTGTTCACCA	778	GTGGCGTGCCTCGAA	779	TGCGCCCGATGAGA	780	CGCCTGTTCACCAAGATTGACACCATTGCGCCCGATG
							TCACCG

EPHA3	NM_005233	781	CAGTAGCCTCAAG	782	TTCGTCCCATATCCAG	783	TATTCCAAATCCGA	784	CAGTAGCCTCAAGCCTGACACTATATACGTATTCCAA
							GCCCGA

EPHB2	NM_004442	785	CAACCAGGCAGCT	786	GTAATGCTGTCCACG	787	CACCTGATGCATGA	788	CAACCAGGCAGCTCCATCGGCAGTGTCCATCATGCA
							TGGACA

EPHB4	NM_004444	789	TGAACGGGGTATCCT	790	AGGTACCTCTCGGTCA	791	CGTCCCATTTGAGC	792	TGAACGGGGTATCCTCCTTAGCCAGGGGCCCGTCCCATT
			CCTTA		GTGG		CTGTCAATGT		TGAGCCTGTCAATGTCACCACTGACCGAGAGGT

ERBB2	NM_004448	793	CGGTGTGAGAAGT	794	CCTCTCGCAAGTGCT	795	CCAGACCATAGCAC	796	CGGTGTGAGAAGTGCAGCAAGCCCTGTGCCCGAGTG
							ACTCGG

ERBB3	NM_001982	797	CGGTTATGTCATGCC	798	GAACTGAGACCCACTG	799	CCTCAAAGGTACTC	800	CGGTTATGTCATGCCAGATACACACCTCAAAGGTACTCC
			AGATACAC		AAGAAAGG		CCTCCTCCCGG		CTCCTCCCGGGAAGGCACCCTTTCTTCAGTGGGTC

ERBB4	NM_005235	801	TGGCTCTTAATCAGT	802	CAAGGCATATCGATCC	803	TGTCCCACGAATAA	804	TGGCTCTTAATCAGTTTCGTTACCTGCCTCTGGAGAATT
			TTCGTTACCT		TCATAAAGT		TGCGTAAATTCTCC		TACGCATTATTCGTGGGACAAAACTTTATGAGGAT
							AG

ERCC1	NM_001983	805	GTCCAGGTGGATG	806	CGGCCAGGATACACA	807	CAGCAGGCCCTCAA	808	GTCCAGGTGGATGTGAAAGATCCCCAGCAGGCCCTC
							GGAGCT

EREG	NM_001432	809	TGCTAGGGTAAAC	810	TGGAGACAAGTCCTG	811	TAAGCCATGGCTGA	812	TGCTAGGGTAAACGAAGGCATAATAAGCCATGGCTG
							CCTCTG

ERG	NM_004449	813	CCAACACTAGGCT	814	CCTCCGCCAGGTCTTT	815	AGCCATATGCCTTC	816	CCAACACTAGGCTCCCCACCAGCCATATGCCTTCTCA
							TCATCT

ESR1	NM_000125	817	CGTGGTGCCCCTC	818	GGCTAGTGGGCGCAT	819	CTGGAGATGCTGGA	820	CGTGGTGCCCCTCTATGACCTGCTGCTGGAGATGCTG
							CGCCC

ESR2	NM_001437	821	TGGTCCATCGCCAGT	822	TGTTCTAGCGATCTTG	823	ATCTGTATGCGGAA	824	TGGTCCATCGCCAGTTATCACATCTGTATGCGGAACCTC
			TATCA		CTTCACA		CCTCAAAAGAGTCC		AAAAGAGTCCCTGGTGTGAAGCAAGATCGCTAGA
							CT

ETV1	NM_004956	825	TCAAACAAGAGCC	826	AACTGCCAGAGCTGA	827	ATCGGGAAGGACCC	828	TCAAACAAGAGCCAGGAATGTATCGGGAAGGACCCA
							ACATAC

ETV4	NM_001986	829	TCCAGTGCCTATG	830	ACTGTCCAAGGGCAC	831	CAGACAAATCGCCA	832	TCCAGTGCCTATGACCCCCCCAGACAAATCGCCATCA
							TCAAGT

EZH2	NM_004456	833	TGGAAACAGCGAAGG	834	CACCGAACACTCCCTA	835	TCCTGACTTCTGTG	836	TGGAAACAGCGAAGGATACAGCCTGTGCACATCCTGACT
			ATACA		GTCC		AGCTCATTGCG		TCTGTGAGCTCATTGCGCGGGACTAGGGAGTGTT

F2R	NM_001992	837	AAGGAGCAAACCA	838	GCAGGGTTTCATTGA	839	CCCGGGCTCAACAT	840	AAGGAGCAAACCATCCAGGTGCCCGGGCTCAACATC
							CACTAC

FAAH	NM_001441	841	GACAGCGTAGTGGTG	842	AGCTGAACATGGACTG	843	TGCCCTTCGTGCAC	844	GACAGCGTGGTGGTGCATGTGCTGAAGCTGCAGGGTGCC
			CATGT		TGGA		ACCAATG		GTGCCCTTCGTGCACACCAATGTTCCACAGTCCA

FABP5	NM_001444	845	GCTGATGGCGAGAAA	846	CTTTCCTTCCCATCCC	847	CCTGATGCTGAACC	848	GCTGATGGCAGAAAAACTCAGACTGTCTGCAACTTTACA
			AACTCA		ACT		AATGCACCAT		GATGGTGCATTGGTTCAGCATCAGGAGTGGGAT

FADD	NM_003824	849	GTTTTCGCGAGAT	850	CTCCGGTGCCTGATTC	851	AACGCGCTCTTGTC	852	GTTTTCGCGAGATAACGGTCGAAAACGCGCTCTTGTC
							GATTTC

FAM107	NM_007177	853	AAGTCAGGGAAAA	854	GCTGGCCCTACAGCT	855	AATTGCCACACTGA	856	AAGTCAGGGAAAACCTGCGGAGAATTGCCACACTGA
							CCAGCG

FAM13C	NM_198215	857	ATCTTCAAAGCGG	858	GCTGGATACCACATG	859	TCCTGACTTTCTCC	860	ATCTTCAAAGCGGAGAGCGGGAGGAGCCACGGAGAA
							GTGGCT

FAM171B	NM_177454	861	CCAGGAAGGAAAAGC	862	GTGGTCTGCCCCTTCT	863	TGAAGATTTTGAAG	864	CCAGGAAGGAAAAGCACTGTTGAAGATTTTGAAGCTAAT
			ACTGT		TTTA		CTAATACATCCCCC		ACATCCCCCACTAAAAGAAGGGGCAGACCAC
							AC

FAM49B	NM_016623	865	AGATGCAGAAGGC	866	GCTGGATTGCCTCTC	867	TGGCCAGCTCCTCT	868	AGATGCAGAAGGCATCTTGGAGGACTTGCAGTCATA
							GTATGA

FAM73A	NM_198549	869	TGAGAAGGTGCGCTA	870	GGCCATTAAAAGCTCA	871	AAGACCTCATGCAG	872	TGAGAAGGTGCGCTATTCAAGTACAGAGACTTTAGCTGA
			TTCAA		GTGC		TTACTCATTCGCC		AGACCTCATGCAGTTACTCATTCGCCGCACTGAG

FAP	NM_004460	873	GTTGGCTCACGTG	874	GACAGGACCGAAACA	875	AGCCACTGCAAACA	876	GTTGGCTCACGTGGGTTACTGATGAACGAGTATGTTT
							TACTCG

FAS	NM_000043	877	GGATTGCTCAACAAC	878	GGCATTAACACTTTTG	879	TCTGGACCCTCCTA	880	GGATTGCTCAACAACCATGCTGGGCATCTGGACCCTCCT
			CATGCT		GACGATAA		CCTCTGGTTCTTAC		ACCTCTGGTTCTTACGTCTGTTGCTAGATTATCG
							GT

FASLG	NM_000639	881	GCACTTTGGGATTCT	882	GCATGTAAGAAGACCC	883	ACAACATTCTCGGT	884	GCACTTTGGGATTCTTTCCATTATGATTCTTTGTTACAG
			TTCCATTAT		TCACTGAA		GCCTGTAACAAAGA		GCACCGAGAATGTTGTATTCAGTGAGGGTCTTCTT
							A

FASN	NM_004104	885	GCCTCTTCCTGTTC	886	GCTTTGCCCGGTAGC	887	TCGCCCACCTACGT	888	GCCTCTTCCTGTTCGACGGCTCGCCCACCTACGTACT
							ACTGGC

FCGR3A	NM_000569	889	GTCTCCAGTGGAA	890	AGGAATGCAGCTACT	891	CCCATGATCTTCAA	892	GTCTCCAGTGGAAGGGAAAAGCCCATGATCTTCAAG
							GCAGGG

FGF10	NM_004465	893	TCTTCCGTCCCTGT	894	AGAGTTGGTGGCCTC	895	ACACCATGTCCTGA	896	TCTTCCGTCCCTGTCACCTGCCAAGCCCTTGGTCAGG
							CCAAGG

FGF17	NM_003867	897	GGTGGCTGTCCTC	898	TCTAGCCAGGAGGAG	899	TTCTCGGATCTCCC	900	GGTGGCTGTCCTCAAAATCTGCTTCTCGGATCTCCCT
							TCAGTC

FGF5	NM_004464	901	GCATCGGTTTCCA	902	AACATATTGGCTTCGT	903	CCATTGACTTTGCC	904	GCATCGGTTTCCATCTGCAGATCTACCCGGATGGCAA
							ATCCGG

FGF6	NM_020996	905	GGGCCATTAATTCTG	906	CCCGGGACATAGTGAT	907	CATCCACCTTGCCT	908	GGGCCATTAATTCTGACCACGTGCCTGAGAGGCAAGGTG
			ACCAC		GAA		CTCAGGCAC		GATGGCCCTGGGACAGAAACTGTTCATCATCTAT

FGF7	NM_002009	909	CCAGAGCAAATGGCT	910	TCCCCTCCTTCCATGT	911	CAGCCCTGAGCGAC	912	CCAGAGCAAATGGCTACAAATGTGAACTGTTCCAGCCCT
			ACAAA		AATC		ACACAAGAAG		GAGCGACACACAAGAAGTTATGATTACATGGAA

FGFR2	NM_000141	913	GAGGGACTGTTGGCA	914	GAGTGAGAATTCGATC	915	TCCCAGAGACCAAC	916	GAGGGACTGTTGGCATGCAGTGCCCTCCCAGAGACCAAC
			TGCA		CAAGTCTTC		GTTCAAGCAGTTG		GTTCAAGCAGTTGGTAGAAGACTTGGATCGAAT

FGFR4	NM_002011	917	CTGGCTTAAGGATGG	918	ACGAGACTCCAGTGCT	919	CCTTTCATGGGGAG	920	CTGGCTTAAGGATGGACAGGCCTTTCATGGGGAGAACCG
			ACAGG		GATG		AACCGCATT		CATTGGAGGCATTCGGCTGCGCCATCAGCACTG

FKBP5	NM_004117	921	CCCACAGTAGAGG	922	GGTTCTGGCTTTCACG	923	TCTCCCCAGTTCCA	924	CCCACAGTAGAGGGGTCTCATGTCTCCCCAGTTCCAC
							CAGCAG

FLNA	NM_001456	925	GAACCTGCGGTGG	926	GAAGACACCCTGGCC	927	TACCAGGCCCATAG	928	GAACCTGCGGTGGACACTTCCGGTGTCCAGTGCTAT
							CACTGG

FLNC	NM_001458	929	CAGGACAATGGTG	930	TGATGGTGTACTCGC	931	ATGTGCTGTCAGCT	932	CAGGACAATGGTGATGGCTCATGTGCTGTCAGCTAC
							ACCTGC

FLT1	NM_002019	933	GGCTCCTGAATCT	934	TCCCACAGCAATACT	935	CTACAGCACCAAGA	936	GGCTCCTGAATCTATCTTTGACAAAATCTACAGCACC
							GCGAC

FLT4	NM_002020	937	ACCAAGAAGCTGA	938	CCTGGAAGCTGTAGC	939	AGCCCGCTGACCAT	940	ACCAAGAAGCTGAGGACCTGTGGCTGAGCCCGCTGA
							GGAAGA

FN1	NM_002026	941	GGAAGTGACAGAC	942	ACACGGTAGCCGGTC	943	ACTCTCAGGCGGTG	944	GGAAGTGACAGACGTGAAGGTCACCATCATGTGGAC
							TCCACA

FOS	NM_005252	945	CGAGCCCTTTGATGA	946	GGAGCGGGCTGTCTCA	947	TCCCAGCATCATCC	948	CGAGCCCTTTGATGACTTCCTGTTCCCAGCATCATCCAG
			CTTCCT		GA		AGGCCCAG		GCCCAGTGGCTCTGAGACAGCCCGCTCC

FOXO1	NM_002015	949	GTAAGCACCATGC	950	GGGGCAGAGGCACTT	951	TATGAACCGCCTGA	952	GTAAGCACCATGCCCCACACCTCGGGTATGAACCGC
							CCCAAG

FOXP3	NM_014009	953	CTGTTTGCTGTCCG	954	GTGGAGGAACTCTGG	955	TGTTTCCATGGCTA	956	CTGTTTGCTGTCCGGAGGCACCTGTGGGGTAGCCAT
							CCCCAC

FOXQ1	NM_033260	957	TGTTTTTGTCGCAA	958	TGGAAAGGTTCCCTG	959	TGATTTATGTCCCT	960	TGTTTTTGTCGCAACTTCCATTGATTTATGTCCCTTCC
							TCCCTC

FSD1	NM_024333	961	AGGCCTCCTGTCC	962	TGTGTGAACCTGGTC	963	CGCACCAAACAAGT	964	AGGCCTCCTGTCCTTCTACAATGCCCGCACCAAACAA
							GCTGCA

FYN	NM_002037	965	GAAGCGCAGATCA	966	CTCCTCAGACACCAC	967	CTGAAGCACGACAA	968	GAAGCGCAGATCATGAAGAAGCTGAAGCACGACAAG
							GCTGGT

G6PD	NM_000402	969	AATCTGCCTGTGG	970	CGAGATGTTGCTGGT	971	CCAGCCTCAGTGCC	972	AATCTGCCTGTGGCCTTGCCCGCCAGCCTCAGTGCCA
							ACTTGA

GABRG2	NM_198904	973	CCACTGTCCTGACAA	974	GAGATCCATCGCTGTG	975	CTCAGCACCATTGC	976	CCACTGTCCTGACAATGACCACCCTCAGCACCATTGCCC
			TGACC		ACAT		CCGGAAAT		GGAAATCGCTCCCCAAGGTCTCCTATGTCAGAGC

GADD45	NM_001924	977	GTGCTGGTGACGA	978	CCCGGCAAAAACAAA	979	TTCATCTCAATGGA	980	GTGCTGGTGACGAATCCACATTCATCTCAATGGAAG
							AGGATC

GADD45	NM_015675	981	ACCCTCGACAAGA	982	TGGGAGTTCATGGGT	983	TGGGAGTTCATGGG	984	ACCCTCGACAAGACCACACTTTGGGACTTGGGAGCT
							TACAGA

GDF15	NM_004864	985	CGCTCCAGACCTA	986	ACAGTGGAAGGACCA	987	TGTTAGCCAAAGAC	988	CGCTCCAGACCTATGATGACTTGTTAGCCAAAGACTG
							TGCCAC

GHR	NM_000163	989	CCACCTCCCACAG	990	GGTGCGTGCCTGTAG	991	CGTGCCTCAGCCTC	992	CCACCTCCCACAGGTTCAGGCGATTCCCGTGCCTCAG
							CTGAGT

GNPTAB	NM_024312	993	GGATTCACATCGC	994	GTTCTTGCATAACAAT	995	CCCTGCTCACATGC	996	GGATTCACATCGCGGAAAGTCCCTGCTCACATGCCTC
							CTCACA

GNRH1	NM_000825	997	AAGGGCTAAATCCAG	998	CTGGATCTCTGTGGCT	999	TCCTGTCCTTCACT	1000	AAGGGCTAAATCCAGGTGTGACGGTATCTAATGATGTCC
			GTGTG		GGT		GTCCTTGCCA		TGTCCTTCACTGTCCTTGCCATCACCAGCCACAG

GPM6B	NM_001001094	1001	ATGTGCTTGGAGTGG	1002	TGTAGAACATAAACAC	1003	CGCTGAGAAACCAA	1004	ATGTGCTTGGAGTGGCCTGGCTGGGTGTGTTTGGTTTCT
			CCT		GGGCA		ACACACCCAG		CAGCGGTGCCCGTGTTTATGTTCTACA

GPNMB	NM_001005340	1005	CAGCCTCGCCTTTAA	1006	TGACAAATATGGCCAA	1007	CAAACAGTGCCCTG	1008	CAGCCTCGCCTTTAAGGATGGCAAACAGTGCCCTGATCT
			GGAT		GCAG		ATCTCCGTTG		CCGTTGGCTGCTTGGCCATATTTGTCA

GPR68	NM_003485	1009	CAAGGACCAGATC	1010	GGTAGGGCAGGAAGC	1011	CTCAGCACCGTGGT	1012	CAAGGACCAGATCCAGCGGCTGGTGCTCAGCACCGT
							CATCTT

GPS1	NM_004127	1013	AGTACAAGCAGGC	1014	GCAGCTCAGGGAAGT	1015	CCTCCTGCTGGCTT	1016	AGTACAAGCAGGCTGCCAAGTGCCTCCTGCTGGCTT
							CCTTTG

GRB7	NM_005310	1017	CCATCTGCATCCA	1018	GGCCACCAGGGTATT	1019	CTCCCCACCCTTGA	1020	CCATCTGCATCCATCTTGTTTGGGTCCCCACCCTTG
							GAAGTG

GREM1	NM_013372	1021	GTGTGGGCAAGGA	1022	GACCTGATTTGGCCT	1023	TCCACCCTCCCTTT	1024	GTGTGGGCAAGGACAAGCAGGATAGTGGAGTGAGAA
							CTCACT

GSK3B	NM_002093	1025	GACAAGGACGGCA	1026	TTGTGGCCTGTCTGG	1027	CCAGGAGTTGCCAC	1028	GACAAGGACGGCAGCAAGGTGACAACAGTGGTGGCA
							CACTGT

GSN	NM_000177	1029	CTTCTGCTAAGCGGT	1030	GGCTCAAAGCCTTGCT	1031	ACCCAGCCAATCGG	1032	CTTCTGCTAAGCGGTACATCGAGACGGACCCAGCCAATC
			ACATCGA		TCAC		GATCGGC		GGGATCGGCGGACGCCCATACCGTGGTGAAGC

GSTM1	NM_000561	1033	AAGCTATGAGGAAAA	1034	GGCCCAGCTTGAATTT	1035	TCAGCCACTGGCTT	1036	AAGCTATGAGGAAAAGAAGTACACGATGGGGGACGCTCC
			GAAGTACACGA		TTCA		CTGTCATAATCAGG		TGATTATGACAGAAGCCAGTGGCTGAATGAAAA
							AG

GSTM2	NM_000848	1037	CTGCAGGCACTCC	1038	CCAAGAAACCATGGC	1039	CTGAAGCTCTACTC	1040	CTGCAGGCACTCCCTGAAATGCTGAAGCTCTACTCAC
							ACAGTT

HDAC1	NM_004964	1041	CAAGTACCACAGCGA	1042	GCTTGCTGTACTCCG	1043	TTCTTGCGCTCCAT	1044	CAAGTACCACAGCGATGACTACATTAAATTCTTGCGCTC
			TGACTACATTA		ACATGTT		CCGTCCAGA		CATCCGTCCAGATAACATGTCGGAGTACAGCAAG

HDAC9	NM_178423	1045	AACCAGGCAGTCACC	1046	CTCTGTCTTCCTGCA	1047	CCCCCTGAAGCTCT	1048	AACCAGGCAGTCACCTTGAGGAAGCAGAGGAAGAGCTTC
			TTGAG		TCGC		TCCTCTGCTT		AGGGGGACCAGGCGATGCAGGAAGACAGAG

HGD	NM_000187	1049	CTCAGGTCTGCCC	1050	TTATTGGTGCTCCGT	1051	CTGAGCAGCTCTCA	1052	CTCAGGTCTGCCCCTACAATCTCTATGCTGAGCAGCT
					G		GGATCG

HIP1	NM_005338	1053	CTCAGAGCCCCAC	1054	GGGTTTCCCTGCCAT	1055	CGACTCACTGACCG	1056	CTCAGAGCCCCACCTGAGCCTGCCGACTCACTGACC
							AGGCCT

HIRIP3	NM_003609	1057	GGATGAGGAAAAG	1058	TCCCTAGCTGACTTTC	1059	CCATTGCTCCTGGT	1060	GGATGAGGAAAAGGGGGATTGGAAACCCAGAACCAG
							TCTGGG

HK1	NM_000188	1061	TACGCACAGAGGC	1062	GAGAGAAGTGCTGGA	1063	TAAGAGTCCGGGAT	1064	TACGCACAGAGGCAAGCAGCTAAGAGTCCGGGATCC
							CCCCAG

HLA-G	NM_002127	1065	CCATCCCCATCAT	1066	CCGCAGCTCCAGTGA	1067	CTGCAAGGACAACC	1068	CCTGCGCGGCTACTACAACCAGAGCGAGGCCAGTTC
							AGGCC

HLF	NM_002126	1069	CACCCTGCAGGTG	1070	GGTACCTAGGAGCAG	1071	TAAGTGATCTGCCC	1072	CACCCTGCAGGTGTCTGAGACTAAGTGATCTGCCCTC
							TCCAGG

HNF1B	NM_000458	1073	TCCCAGCATCTCA	1074	CGTACCAGGTGTACA	1075	CCCCTATGAAGACC	1076	TCCCAGCATCTCAACAAGGGCACCCCTATGAAGACC
							CAGAAG

HPS1	NM_000195	1077	GCGGAAGCTGTAT	1078	TTCGGATAAGATGAC	1079	CAGTCACCAGCCCA	1080	GCGGAAGCTGTATGTGCTCAAGTACCTGTTTGAAGT
							AAGTGC

HRAS	NM_005343	1081	GGACGAATACGAC	1082	GCACGTCTCCCCATC	1083	ACCACCTGCTTCCG	1084	GGACGAATACGACCCCACTATAGAGGATTCCTACCG
							GTAGGA

HSD17B10	NM_004493	1085	CCAGCGAGTTCTTGA	1086	ATCTCACCAGCCACCA	1087	TCATGGGCACCTTC	1088	CCACCAGACAAGACCGATTCGCTGGCCTCCATTTCTTCA
			TGTGA		GG		AATGTGATCC		ACCCAGTGCCTGTCATGAAACTTGTGG

HSD17B2	NM_002153	1089	GCTTTCCAAGTGG	1090	TGCCTGCGATATTTGT	1091	AGTTGCTTCCATCC	1092	GCTTTCCAAGTGGGGAATTAAAGTTGCTTCCATCCAA
							AACCTG

HSD17B3	NM_000197	1093	GGGACGTCCTGGAAC	1094	TGGAGAATCTCACGCA	1095	CTTCATCCTCACAG	1096	GGGACGTCCTGGAACAGTTCTTCATCCTCACAGGGCTGC
			AGT		CTTC		GGCTGCTGGT		TGGTGTGCCTGGCCTGCCTGGCGAAGTGCGTGAG

HSD17B4	NM_000414	1097	CGGGAAGCTTCAG	1098	ACCTCAGGCCCAATA	1099	AGGCGGCGTCCTAT	1100	CGGGAAGCTTCAGAGTACCTTTGTATTTGAGGAAAT
							TTCCTC

HSD3B2	NM_000198	1101	GCCTTCCTTTAACC	1102	GGAGTAAATTGGGCT	1103	ACTTCCAGCAGGAA	1104	GCCTTCCTTTAACCCTGATGTACTGGATTGGCTTCCT
							GCCAAT

HSP90AB1	NM_007355	1105	GCATTGTGACCAGCA	1106	GAAGTGCCTGGGCTTT	1107	ATCCGCTCCATATT	1108	GCATTGTGACCAGCACCTACGGCTGGACAGCCAATATGG
			CCTAC		CAT		GGCTGTCCAG		AGCGGATCATGAAAGCCCAGGCACTTC

HSPA5	NM_005347	1109	GGCTAGTAGAACTGG	1110	GGTCTGCCCAAATGCT	1111	TAATTAGACCTAGG	1112	GGCTAGTAGAACTGGATCCCAACACCAAACTCTTAATTA
			ATCCCAACA		TTTC		CCTCAGCTGCACTG		GACCTAGGCCTCAGCTGCACTGCCCGAAAAGCA
							C

HSPA8	NM_006597	1113	CCTCCCTCTGGTGGT	1114	GCTACATCTACACTTG	1115	CTCAGGGCCCACCA	1116	CCTCCCTCTGGTGGTGCTTCCTCAGGGCCCACCATTGAA
			GCTT		GTTGGCTTAA		TTGAAGAGGTTG		GAGGTTGATTAAGCCAACCAAGTGTAGATGTAGC

HSPB1	NM_001540	1117	CCGACTGGAGGAGCA	1118	ATGCTGGCTGACTCTG	1119	CGCACTTTTCTGAG	1120	CCGACTGGAGGAGCATAAAAGCGCAGCCGAGCCCAGCGC
			TAAA		CTC		CAGACGTCCA		CCCGCACTTTTCTGAGCAGACGTCCAGAGCAGA

HSPB2	NM_001541	1121	CACCACTCCAGAG	1122	TGGGACCAAACCATA	1123	CACCTTTCCCTTCC	1124	CACCACTCCAGAGGTAGCAGCATCCTTGGGGGAAGG
							CCCAAG

HSPE1	NM_002157	1125	GCAAGCAACAGTAGT	1126	CCAACTTTCACGCTAA	1127	TCTCCACCCTTTCC	1128	GCAAGCAACAGTAGTCGCTGTTGGATCGGGTTCTAAAGG
			CGCTG		CTGGT		TTTAGAACCCG		AAAGGGTGGAGAGATTCAACCAGTTAGCGTGAA

HSPG2	NM_005529	1129	GAGTACGTGTGCC	1130	CTCAATGGTGACCAG	1131	CAGCTCCGTGCCTC	1132	GAGTACGTGTGCCGAGTGTTGGGCAGCTCCGTGCCT
							TAGAGG

ICAM1	NM_000201	1133	GCAGACAGTGACCAT	1134	CTTCTGAGACCTCTGG	1135	CCGGCGCCCAACGT	1136	GCAGACAGTGACCATCTACAGCTTTCCGGCGCCCAACGT
			CTACAGCTT		CTTCGT		GATTCT		GATTCTGACGAAGCCAGAGGTCTCAGAAG

IER3	NM_003897	1137	GTACCTGGTGCGCGA	1138	GCGTCTCCGCTGTAGT	1139	TCAAGTTGCCTCGG	1140	GTACCTGGTGCGCGAGAGCGTATCCCCAACTGGGACTTC
			GAG		GTT		AAGTCCCAGT		CGAGGCAACTTGAACTCAGAACACTACAGCGGA

IFI30	NM_006332	1141	ATCCCATGAAGCC	1142	GCACCATTCTTAGTG	1143	AAAATTCCACCCCA	1144	ATCCCATGAAGCCCAGATACACAAAATTCCACCCCA
							TGATCA

IFIT1	NM_001548	1145	TGACAACCAAGCA	1146	CAGTCTGCCCATGTG	1147	AAGTTGCCCCAGGT	1148	TGACAACCAAGCAAATGTGAGGAGTCTGGTGACCTG
							CACCAG

IFNG	NM_000619	1149	GCTAAAACAGGGAAG	1150	CAACCATTACTGGGAT	1151	TCGACCTCGAAACA	1152	GCTAAAACAGGGAAGCGAAAAAGGAGTCAGATGCTGTTT
			CGAAA		GCTC		GCATCTGACTCC		CGAGGTCGAAGAGCATCCCAGTAATGGTTG

IGF1	NM_000618	1153	TCCGGAGCTGTGA	1154	CGGACAGAGCGAGCT	1155	TGTATTGCGCACCC	1156	TCCGGAGCTGTGATCTAAGGAGGCTGGAGATGTATT
							CTCAAG

IGF1R	NM_000875	1157	GCATGGTAGCCGAAG	1158	TTTCCGGTAATAGTCT	1159	CGCGTCATACCAAA	1160	GCATGGTAGCCGAAGATTTCACAGTCAAAATCGGAGATT
			ATTTCA		GTCTCATAGATATC		ATCTCCGATTTTGA		TTGGTATGACGCGAGATATCTATGAGACAGACTA

IGF2	NM_000612	1161	CCGTGCTTCCGGA	1162	TGGACTGCTTCCAGG	1163	TACCCCGTGGGCAA	1164	CCGTGCTTCCGGACAACTTCCCCAGATACCCCGTGGG
							GTTCTT

IGFBP2	NM_000597	1165	GTGGACAGCACCA	1166	CCTTCATACCCGACTT	1167	CTTCCGGCCAGCAC	1168	GTGGACAGCACCATGAACATGTTGGGCGGGGGAGGC
							TGCCTC

IGFBP3	NM_000598	1169	ACATCCCAACGCA	1170	CCACGCCCTTGTTTCA	1171	ACACCACAGAAGGC	1172	ACATCCCAACGCATGCTCCTGGAGCTCACAGCCTTCT
							TGTGA

IGFBP5	NM_000599	1173	TGGACAAGTACGG	1174	CGAAGGTGTGGCACT	1175	CCCGTCAACGTACT	1176	TGGACAAGTACGGGATGAAGCTGCCAGGCATGGAGT
							CCATGC

IGFBP6	NM_002178	1177	TGAACCGCAGAGACC	1178	GTCTTGGACACCCGCA	1179	ATCCAGGCACCTCT	1180	TGAACCGCAGAGACCAACAGAGGAATCCAGGCACCTCTA
			AACAG		GAAT		ACCACGCCCTC		CCACGCCCTCCCAGCCCAATTCTGCGGGTGTCCA

IL10	NM_000572	1181	CTGACCACGCTTT	1182	CCAAGCCCAGAGACA	1183	TTGAGCTGTTTTCC	1184	CTGACCACGCTTTCTAGCTGTTGAGCTGTTTTCCCTG
							CTGACC

IL11	NM_000641	1185	TGGAAGGTTCCAC	1186	TCTTGACCTTGCAGCT	1187	CCTGTGATCAACAG	1188	TGGAAGGTTCCACAAGTCACCCTGTGATCAACAGTA
							TACCCG

IL17A	NM_002190	1189	TCAAGCAACACTC	1190	CAGCTCCTTTCTGGGT	1191	TGGCTTCTGTCTGA	1192	TCAAGCAACACTCCTAGGGCCTGGCTTCTGTCTGATC
							TCAAGG

IL1A	NM_000575	1193	GGTCCTTGGTAGA	1194	GGATGGAGCTTCAGG	1195	TCTCCACCCTGGCC	1196	GGTCCTTGGTAGAGGGCTACTTTACTGTAACAGGGC
							CTGTTA

IL1B	NM_000576	1197	AGCTGAGGAAGAT	1198	GGAAAGAAGGTGCTC	1199	TGCCCACAGACCTT	1200	AGCTGAGGAAGATGCTGGTTCCCTGCCCACAGACCT
							CCAGGA

IL2	NM_000586	1201	ACCTCAACTCCTGCC	1202	CACTGTTTGTGACAAG	1203	TGCAACTCCTGTCT	1204	ACCTCAACTCCTGCCACAATGTACAGGATGCAACTCCTG
			ACAAT		TGCAAG		TGCATTGCAC		TCTTGCATTGCACTAAGTCTTGCACTTGTCACAAA

IL6	NM_000600	1205	CCTGAACCTTCCA	1206	ACCAGGCAAGTCTCC	1207	CCAGATTGGAAGCA	1208	CCTGAACCTTCCAAAGATGGCTGAAAAAGATGGATG
							TCCATC

IL6R	NM_000565	1209	CCAGCTTATCTCA	1210	CTGGCGTAGAACCTT	1211	CCTTTGGCTTCACG	1212	CCAGCTTATCTCAGGGGTGTGCGGCCTTTGGCTTCAC
							GAAGAG

IL6ST	NM_002184	1213	GGCCTAATGTTCC	1214	AAAATTGTGCCTTGG	1215	CATATTGCCCAGTG	1216	GGCCTAATGTTCCAGATCCTTCAAAGAGTCATATTGC
							GTCACC

IL8	NM_000584	1217	AAGGAACCATCTCAC	1218	ATCAGGAAGGCTGCCA	1219	TGACTTCCAAGCTG	1220	AAGGAACCATCTCACTGTGTGTAAACATGACTTCCAAGC
			TGTGTGTAAAC		AGAG		GCCGTGGC		TGGCCGTGGCTCTCTTGGCAGCCTTCCTGAT

ILF3	NM_004516	1221	GACACGCCAAGTG	1222	CTCAAGACCCGGATC	1223	ACACAAGACTTCAG	1224	GACACGCCAAGTGGTTCCAGGCCAGAGCCAACGGGC
							CCCGTT

ILK	NM_001014794	1225	CTCAGGATTTTCTCG	1226	AGGAGCAGGTGGAGAC	1227	ATGTGCTCCCAGTG	1228	CTCAGGATTTTCTCGCATCCAAATGTGCTCCCAGTGCTA
			CATCC		TGG		CTAGGTGCCT		GGTGCCTGCCAGTCTCCACCTGCTCCT

IMMT	NM_006839	1229	CTGCCTATGCCAG	1230	GCTTTTCTGGCTTCCT	1231	CAACTGCATGGCTC	1232	CTGCCTATGCCAGACTCAGAGGAATCGAACAGGCTG
							TGAACA

ING5	NM_032329	1233	CCTACAGCAAGTG	1234	CATCTCGTAGGTCTG	1235	CCAGCTGCACTTTG	1236	CCTACAGCAAGTGCAAGGAATACAGTGACGACAAAG
							TCGTCA

INHBA	NM_002192	1237	GTGCCCGAGCCAT	1238	CGGTAGTGGTTGATG	1239	ACGTCCGGGTCCTC	1240	GTGCCCGAGCCATATAGCAGGCACGTCCGGGTCCTC
							ACTGTC

INSL4	NM_002195	1241	CTGTCATATTGCCC	1242	CAGATTCCAGCAGCC	1243	TGAGAAGACATTCA	1244	CTGTCATATTGCCCCATGCCTGAGAAGACATTCACCA
							CCACCA

ITGA1	NM_181501	1245	GCTTCTTCTGGAG	1246	CCTGTAGATAATGAC	1247	TTGCTGGACAGCCT	1248	GCTTCTTCTGGAGATGTGCTCTATATTGCTGGACAGC
							CGGTAC

ITGA3	NM_002204	1249	CCATGATCCTCAC	1250	GAAGCTTTGTAGCCG	1251	CACTCCAGACCTCG	1252	CCATGATCCTCACTCTGCTGGTGGACTATACACACTCCA
							CTTAGC

ITGA4	NM_000885	1253	CAACGCTTCAGTG	1254	GTCTGGCCGGGATTC	1255	CGATCCTGCATCTG	1256	CAACGCTTCAGTGATCAATCCCGGGGCGATTTACAG
							TAAATC

ITGA5	NM_002205	1257	AGGCCAGCCCTAC	1258	GTCTTCTCCACAGTCC	1259	TCTGAGCCTTGTCC	1260	AGGCCAGCCCTACATTATCAGAGCAAGAGCCGGATA
							TCTATC

ITGA6	NM_000210	1261	CAGTGACAAACAG	1262	GTTTAGCCTCATGGG	1263	TCGCCATCTTTTGT	1264	CAGTGACAAACAGCCCTTCCAACCCAAGGAATCCCA
							GGGATT

ITGA7	NM_002206	1265	GATATGATTGGTCGC	1266	AGAACTTCCATTCCCC	1267	CAGCCAGGACCTGG	1268	GATATGATTGGTCGCTGCTTTGTGCTCAGCCAGGACCTG
			TGCTTTG		ACCAT		CCATCCG		GCCATCCGGGATGAGTTGGATGGTGGGGAATGGA

ITGAD	NM_005353	1269	GAGCCTGGTGGAT	1270	ACTGTCAGGATGCCC	1271	CAACTGAAAGGCCT	1272	GAGCCTGGTGGATCCCATCGTCCAACTGAAAGGCCT
							GACGTT

ITGB3	NM_000212	1273	ACCGGGAGCCCTACA	1274	CCTTAAGCTCTTTCAC	1275	AAATACCTGCAACC	1276	ACCGGGGAGCCCTACATGACGAAAATACCTGCAACCGTT
			TGAC		TGACTCAATCT		GTTACTGCCGTGAC		ACTGCCGTGACGAGATTGAGTCAGTGAAAGAGC

ITGB4	NM_000213	1277	CAAGGTGCCCTCA	1278	GCGCACACCTTCATC	1279	CACCAACCTGTACC	1280	CAAGGTGCCCTCAGTGGAGCTCACCAACCTGTACCC
							CGTATT

ITGB5	NM_002213	1281	TCGTGAAAGATGA	1282	GGTGAACATCATGAC	1283	TGCTATGTTTCTAC	1284	TCGTGAAAGATGACCAGGAGGCTGTGCTATGTTTCTA
							AAAACC

ITPR1	NM_002222	1285	GAGGAGGTGTGGG	1286	GTAATCCCATGTCCG	1287	CCATCCTAACGGAA	1288	GAGGAGGTGTGGGTGTTCCGCTTCCATCCTAACGGA
							CGAGCT

ITPR3	NM_002224	1289	TTGCCATCGTGTC	1290	ATGGAGCTGGCGTCA	1291	TCCAGGTCTCGGAT	1292	TTGCCATCGTGTCAGTGCCCGTGTCTGAGATCCGAGA
							CTCAGA

ITSN1	NM_003024	1293	TAACTGGGATGCA	1294	CTCTGCCTTAACTGGC	1295	AGCCCTCTCTCACC	1296	TAACTGGGATGCATGGGCAGCCCAGCCCTCTCTCAC
							GTTCCA

JAG1	NM_000214	1297	TGGCTTACACTGG	1298	GCATAGCTGTGAGAT	1299	ACTCGATTTCCCAG	1300	TGGCTTACACTGGCAATGGTAGTTTCTGTGGTTGGCT
							CCAACC

JUN	NM_002228	1301	GACTGCAAAGATGGA	1302	TAGCCATAAGGTCCGC	1303	CTATGACGATGCCC	1304	GACTGCAAAGATGGAAACGACCTTCTATGACGATGCCCT
			AACGA		TCTC		TCAACGCCTC		CAACGCCTCGTTCCTCCCGTCCGAGAGCGGACCT

JUNB	NM_002229	1305	CTGTCAGCTGCTG	1306	AGGGGGTGTCCGTAA	1307	CAAGGGACACGCCT	1308	CTGTCAGCTGCTGCTTGGGGTCAAGGGACACGCCTT
							TCTGAA

KCNN2	NM_021614	1309	TGTGCTATTCATCC	1310	GGGCATAGGAGAAGG	1311	TTATACATTCACAT	1312	TGTGCTATTCATCCCATACCTGGGAATTATACATTCA
							GGACGG

KCTD12	NM_138444	1313	AGCAGTTACTGGC	1314	TGGAGACCTGAGCAG	1315	ACTCTTAGGCGGCA	1316	AGCAGTTACTGGCAAGAGGGAGAAAGGACGCTGCCG
							GCGTCC

KHDRBS	NM_006558	1317	CGGGCAAGAAGAG	1318	CTGTAGACGCCCTTT	1319	CAAGACACAAGGCA	1320	CGGGCAAGAAGAGTGGACTAACTCAAGACACAAGGC
							CCTTCA

KIAA019	NM_014846	1321	CAGACACCAGCTC	1322	AACATTGTGAGGCGG	1323	TCCCCAGTGTCCAG	1324	CAGACACCAGCTCTGAGGCCAGTTAATCATCCCCAG
							GCACAG

KIAA024	NM_014734	1325	CCGTGGGACATGG	1326	GAAGCAAGTCCGTCT	1327	TCCGCTAGTGATCC	1328	CCGTGGGACATGGAGTGTTCCTTCCGCTAGTGATCCT
							TTTGCA

KIF4A	NM_012310	1329	AGAGCTGTCTCC	1330	GCTGGTCTTGCTCTGT	1331	CAGGTCAGCAAACT	1332	AGAGCTGGTCTCCTCCAAAATACAGGTCAGCAAACT
							TGAAAG

KIT	NM_000222	1333	GAGGCAACTGCTTAT	1334	GGCACTCGGCTTGAGC	1335	TTACAGCGACAGTC	1336	GAGGCAACTGCTTATGGCTTAATTAAGTCAGATGCGGCC
			GGCTTAATTA		AT		ATGGCCGCAT		ATGACTGTCGCTGTAAAGATGCTCAAGCCGAGT

KLC1	NM_182923	1337	AGTGGCTACGGGA	1338	TGAGCCACAGACTGC	1339	CAACACGCAGCAGA	1340	AGTGGCTACGGGATGAACTGGCCAACACGCAGCAGA
							AACTG

KLF6	NM_001300	1341	CACGAGACCGGCT	1342	GCTCTAGGCAGGTCT	1343	AGTACTCCTCCAGA	1344	CACGAGACCGGCTACTTCTCGGCGCTGCCGTCTCTGG
							GACGGC

KLK1	NM_002257	1345	AACACAGCCCAGTTT	1346	CCAGGAGGCTCATGTT	1347	TCAGTGAGAGCTTC	1348	AACACAGCCCAGTTTGTTCATGTCAGTGAGAGCTTCCCA
			GTTCA		GAAG		CCACACCCTG		CACCCTGGCTTCAACATGAGCCTCCTGG

KLK10	NM_002776	1349	GCCCAGAGGCTCC	1350	CAGAGGTTTGAACAG	1351	CCTCTTCCTCCCCA	1352	GCCCAGAGGCTCCATCGTCCATCCTCTTCCTCCCCAG
							GTCGGC

KLK11	NM_006853	1353	CACCCCGGCTTCA	1354	CATCTTCACCAGCAT	1355	CCTCCCCAACAAAG	1356	CACCCCGGCTTCAACAACAGCCTCCCCAACAAAGAC
							ACCACC

KLK14	NM_022046	1357	CCCCTAAAATGTT	1358	CTCATCCTCTTGGCTC	1359	CAGCACTTCAAGTC	1360	CCCCTAAAATGTTCCTCCTGCTGACAGCACTTCAAGT
							CTGGCT

KLK2	NM_005551	1361	AGTCTCGGATTGT	1362	TGTACACAGCCACCT	1363	TTGGGAATGCTTCT	1364	AGTCTCGGATTGTGGGAGGCTGGGAGTGTGAGAAGC
							CACACT

KLK3	NM_001648	1365	CCAAGCTTACCAC	1366	AGGGTGAGGAAGACA	1367	ACCCACATGGTGAC	1368	CCAAGCTTACCACCTGCACCCGGAGAGCTGTGTCAC
							ACAGCT

KLRK1	NM_007360	1369	TGAGAGCCAGGCT	1370	ATCCTGGTCCTCTTTG	1371	TGTCTCAAAATGCC	1372	TGAGAGCCAGGCTTCTTGTATGTCTCAAAATGCCAGC
							AGCCTT

KPNA2	NM_002266	1373	TGATGGTCCAAAT	1374	AAGCTTCACAAGTTG	1375	ACTCCTGTTTTCAC	1376	TGATGGTCCAAATGAACGAATTGGCATGGTGGTGAA
							CACCAT

KRT1	NM_006121	1377	TGGACAACAACCG	1378	TATCCTCGTACTGGG	1379	CCTCAGCAATGATG	1380	TGGACAACAACCGCAGTCTCGACCTGGACAGCATCA
							CTGTCC

KRT15	NM_002275	1381	GCCTGGTTCTTCA	1382	CTTGCTGGTCTGGATC	1383	TGAACAAAGAGGTG	1384	GCCTGGTTCTTCAGCAAGACTGAGGAGCTGAACAAA
							GCCTCC

KRT18	NM_000224	1385	AGAGATCGAGGCT	1386	GGCCTTTTACTTCCTC	1387	TGGTTCTTCTTCAT	1388	AGAGATCGAGGCTCTCAAGGAGGAGCTGCTCTTCAT
							GAAGAG

KRT2	NM_000423	1389	CCAGTGACGCCTC	1390	GGGCATGGCTAGAAG	1391	ACCTAGACAGCACA	1392	CCAGTGACGCCTCTGTGTTCTGGGGCGGAATCTGTGC
							GATTCC

KRT5	NM_000424	1393	TCAGTGGAGAAGG	1394	TGCCATATCCAGAGG	1395	CCAGTCAACATCTC	1396	TCAGTGGAGAAGGAGTTGGACCAGTCAACATCTCTG
							TGTTGT

KRT75	NM_004693	1397	TCAAAGTCAGGTACG	1398	ACGCTCCTTTTTCAGG	1399	TTCATTCTCAGCAG	1400	TCAAAGTCAGGTACGAAGATGAAATTAACAAGCGCACAG
			AAGATGAAATT		GCTACAA		CTGTGCGCTTGT		CTGCTGAGAATGAATTTGTAGCCCTGAAAAAGG

KRT76	NM_015848	1401	ATCTCCAGACTGCTG	1402	TCAGGGAATTAGGGGA	1403	TCTGGGCTTCAGAT	1404	ATCTCCAGACTGCTGGTTCCCAGGGAACCCTCCCTACAT
			GTTCC		CAGA		CCTGACTCCC		CTGGGCTTCAGATCCTGACTCCCTTCTGTCCCCTA

KRT8	NM_002273	1405	GGATGAAGCTTACAT	1406	CATATAGCTGCCTGAG	1407	CGTCGGTCAGCCCT	1408	GGATGAAGCTTACATGAACAAGGTAGAGCTGGAGTCTCG
			GAACAAGGTAG		GAAGTTGAT		TCCAGGC		CCTGGAAGGGCTGACCGACGAGATCAACTTCCT

L1CAM	NM_000425	1409	CTTGCTGGCCAAT	1410	TGATTGTCCGCAGTC	1411	ATCTACGTTGTCCA	1412	CTTGCTGGCCAATGCCTACATCTACGTTGTCCAGCTG
							GCTGCC

LAG3	NM_002286	1413	GCCTTAGAGCAAG	1414	CGGTTCTTGCTCCAGC	1415	TCTATCTTGCTCTG	1416	GCCTTAGAGCAAGGGATTCACCCTCCGCAGGCTCAG
							AGCCTG

LAMA3	NM_000227	1417	CCTGTCACTGAAG	1418	TGGGTTACTGGTCAG	1419	ATTCAGACTGACAG	1420	CCTGTCACTGAAGCCTTGGAAGTCCAGGGGCCTGTC
							GCCCCT

LAMA4	NM_002290	1421	GATGCACTGCGGT	1422	CAGAGGATACGCTCA	1423	CTCTCCATCGAGGA	1424	GATGCACTGCGGTTAGCAGCGCTCTCCATCGAGGAA
							AGGCAA

LAMA5	NM_005560	1425	CTCCTGGCCAACA	1426	ACACAAGGCCCAGCC	1427	CTGTTCCTGGAGCA	1428	CTCCTGGCCAACAGCACTGCACTAGAAGAGGCCATG
							TGGCCT

LAMB1	NM_002291	1429	CAAGGAGACTGGG	1430	CGGCAGAACTGACAG	1431	CAAGTGCCTGTACC	1432	CAAGGAGACTGGGAGGTGTCTCAAGTGCCTGTACCA
							ACACGG

LABM3	NM_000228	1433	ACTGACCAAGCCT	1434	GTCACACTTGCAGCA	1435	CCACTCGCCATACT	1436	ACTGACCAAGCCTGAGACCTACTGCACCCAGTATGG
							GGGTGC

LAMC1	NM_002293	1437	GCCGTGATCTCAG	1438	ACCTGCTTGCCCAAG	1439	CCTCGGTACTTCAT	1440	GCCGTGATCTCAGACAGCTACTTTCCTCGGTACTTCA
							TGCTCC

LAMC2	NM_005562	1441	ACTCAAGCGGAAATT	1442	ACTCCCTGAAGCCGAG	1443	AGGTCTTATCAGCA	1444	ACTCAAGCGGAAATTGAAGCAGATAGGTCTTATCAGCAC
			GAAGCA		ACACT		CAGTCTCCGCCTCC		AGTCTCCGCCTCCTGGATTCAGTGTCTCGGCTTC

LAPTM5	NM_006762	1445	TGCTGGACTTCTG	1446	TGAGATAGGTGGGCA	1447	TCCTGACCCTCTGC	1448	TGCTGGACTTCTGCCTGAGCATCCTGACCCTCTGCAG
							AGCTCC

LGALS3	NM_002306	1449	AGCGGAAAATGGC	1450	CTTGAGGGTTTGGGT	1451	ACCCAGATAACGCA	1452	AGCGGAAAATGGCAGACAATTTTTCGCTCCATGATG
							TCATGG

LIG3	NM_002311	1453	GGAGGTGGAGAAG	1454	ACAGGTGTCATAGC	1455	CTGGACGCTCAGAG	1456	GGAGGTGGAGAAGGAGCCGGGCCAGAGACGAGCTCT
							CTCGTC

LIMS1	NM_004987	1457	TGAACAGTAATGG	1458	TTCTGGGAACTGCTG	1459	ACTGAGCGCACACG	1460	TGAACAGTAATGGGGAGCTGTACCATGAGCAGTGTT
							AAACA

LOX	NM_002317	1461	CCAATGGGAGAAC	1462	CGCTGAGGCTGGTAC	1463	CAGGCTCAGCAAGC	1464	CCAATGGGAGAACAACGGGCAGGTGTTCAGCTTGCT
							TGAACA

LRP1	NM_002332	1465	TTTGGCCCAATGGGC	1466	GTCTCGATGCGGTCGT	1467	TCCCGGCTGGGCGC	1468	TTTGGCCCAATGGGCTAAGCCTGGACATCCCGGCTGGGC
			TAAG		AGAAG		CTCTACT		GCCTCTACTGGGTGGATGCCTTCTACGACCGCAT

LTBP2	NM_000428	1469	GCACACCCATCCT	1470	GATGGCTGGCCACGT	1471	CTTTGCAGCCCTCA	1472	GCACACCCATCCTTGAGTCTCCTTTGCAGCCCTCAGA
							GAACTC

LUM	NM_002345	1473	GGCTCTTTTGAAGGA	1474	AAAAGCAGCTGAAACA	1475	CCTGACCTTCATCC	1476	GGCTCTTTTGAAGGATTGGTAAACCTGACCTTCATCCAT
			TTGGTAA		GCATC		ATCTCCAGCA		CTCCAGCACAATCGGCTGAAAGAGGATGCTGTTT

MAGEA4	NM_002362	1477	GCATCTAACAGCC	1478	CAGAGTGAAGAATGG	1479	CAGCTTCCCTTGCC	1480	GCATCTAACAGCCCTGTGCAGCAGCTTCCCTTGCCTC
							TCGTGT

MANF	NM_006010	1481	CAGATGTGAAGCC	1482	AAGGGAATCCCCTCA	1483	TTCCTGATGATGCT	1484	CAGATGTGAAGCCTGGAGCTTTCCTGATGATGCTGG
							GGCCCT

MAOA	NM_000240	1485	GTGTCAGCCAAAG	1486	CGACTACGTCGAACA	1487	CCGCGATACTCGCC	1488	GTGTCAGCCAAAGCATGGAGAATCAAGAGAAGGCGA
							TTCTCT

MAP3K5	NM_005923	1489	AGGACCAAGAGGC	1490	CCTGTGGCCATTTCA	1491	CAGCCCAGAGACCA	1492	AGGACCAAGAGGCTACGGAAAAGCAGCAGACATCTG
							GATGTC

MAP3K7	NM_145333	1493	CAGGCAAGAACTAGT	1494	CCTGTACCAGGCGAGA	1495	TGCTGGTCCTTTTC	1496	CAGGCAAGAACTAGTTGCAGAACTGGACCAGGATGAAAA
			TGCAGAA		TGTAT		ATCCTGGTCC		GGACCAGCAAAATACATCTCGCCTGGTACAGG

MAP4K4	NM_004834	1497	TCGCCGAGATTTC	1498	CTGTTGTCTCCGAAG	1499	AACGTTCCTTGTTC	1500	TCGCCGAGATTTCCTGAGACTGCAGCAGGAGAACAA
							TCCTGC

MAP7	NM_003980	1501	GAGGAACAGAGGT	1502	CTGCCAACTGGCTTTC	1503	CATGTACAACAAAC	1504	GAGGAACAGAGGTGTCTGCACTTCCATGTACAACAA
							GCTCCG

MAPKAPK3	NM_004635	1505	AAGCTGCAGAGATAA	1506	GTGGGCAATGTTATGG	1507	ATTGGCACTGCCAT	1508	AAGCTGCAGAGATAATGCGGGATATTGGCACTGCCATCC
			TGCGG		CTG		CCAGTTTCTG		AGTTTCTGCACAGCCATAACATTGCCCAC

MCM2	NM_004526	1509	GACTTTTGCCCGCTA	1510	GCCACTAACTGCTTCA	1511	ACAGCTCATTGTTG	1512	GACTTTTGCCCGCTACCTTTCATTCCGCGTGACAACAAT
			CCTTTC		GTATGAAGAG		TCACGCCGGA		GAGCTGTTGCTCTTCATACTGAAGCAGTTAGTGG

MCM3	NM_002388	1513	GGAGAACAATCCC	1514	ATCTCCTGGATGGTG	1515	TGGCCTTTCTGTCT	1516	GGAGAACAATCCCCTTGAGACAGAATATGGCCTTTC
							ACAAGG

MCM6	NM_005915	1517	TGATGGTCCTATGTG	1518	TGGGACAGGAAACACA	1519	CAGGTTTCATACCA	1520	TGATGGTCCTATGTGTCACATTCATCACAGGTTTCATAC
			TCACATTCA		CCAA		ACACAGGCTTCAGC		CAACACAGGCTTCAGCACTTCCTTTGGTGTGTTTC

MDK	NM_002391	1521	GGAGCCGACGTGCA	1522	GACTTTGGTGCCTGT	1523	ATCACACGCACCCC	1524	GGAGCCGACTGCAAGTACAAGTTTGAGAACTGGGGT
							AGTTCT

MDM2	NM_002392	1525	CTACAGGGACGCC	1526	ATCCAACCAATCACC	1527	CTTACACCAGCATC	1528	CTACAGGGACGCCATCGAATCCGGATCTTGATGCTG
							AAGATC

MELK	NM_014791	1529	AGGATCGCCTGTC	1530	TGCACATAAGCAACA	1531	CCCGGGTTGTCTTC	1532	AGGATCGCCTGTCAGAAGAGGAGACCCGGGTTGTCT
							CGTCAG

MET	NM_000245	1533	GACATTTCCAGTCCT	1534	CTCCGATCGCACACAT	1535	TGCCTCTCTGCCCC	1536	GACATTTCCAGTCCTGCAGTCAATGCCTCTCTGCCCCAC
			GCAGTCA		TTGT		ACCCTTTGT		CCTTTGTTCAGTGTGGCTGGTGCCACGACAAATGT

MGMT	NM_002412	1537	GTGAAATGAAACG	1538	GACCCTGCTCACAAC	1539	CAGCCCTTTGGGGA	1540	GTGAAATGAAACGCACCACACTGGACAGCCCTTTGG
							AGCTGG

MGST1	NM_020300	1541	ACGGATCTACCACAC	1542	TCCATATCCAACAAAA	1543	TTTGACACCCCTTC	1544	ACGGATCTACCACACCATTGCATATTTGACACCCCTTCC
			CATTGC		AAACTCAAAG		CCCAGCCA		CCAGCCAAATAGAGCTTTGAGTTTTTTTGTTGGAT

MICA	NM_000247	1545	ATGGTGAATGTCA	1546	AAGCCAGAAGCCCTG	1547	CGAGGCCTCAGAGG	1548	ATGGTGAATGTCACCCGCAGCGAGGCCTCAGAGGGC
							GCAAC

MKI67	NM_002417	1549	GATTGCACCAGGG	1550	TCCAAAGTGCCTCTG	1551	CCACTCTTCCTTGA	1552	GATTGCACCAGGGCAGAACAGGGGAGGGTGTTCAAG
							ACACCC

MLXIP	NM_014938	1553	TGCTTAGCTGGCA	1554	CAGCCTACTCTCCAT	1555	CATGAGATGCCAGG	1556	TGCTTAGCTGGCATGTGGCCGCATGAGATGCCAGGA
							AGACCC

MMP11	NM_005940	1557	CCTGGAGGCTGCAAC	1558	TACAATGGCTTTGGAG	1559	ATCCTCCTGAAGCC	1560	CCTGGAGGCTGCAACATACCTCAATCCTGTCCCAGGCCG
			ATACC		GATAGCA		CTTTTCGCAGC		GATCCTCCTGAAGCCCTTTTCGCAGCACTGCTAT

MMP2	NM_004530	1561	CAGCCAGAAGCGG	1562	AGACACCATCACCTG	1563	AAGTCCGAATCTCT	1564	CAGCCAGAAGCGGAAACCTTAAAAAGTCCGATCTCT
							GCTCCC

MMP7	NM_002423	1565	GGATGGTAGCAGTCT	1566	GGAATGTCCCATACCC	1567	CCTGTATGCTGCAA	1568	GGATGGTAGCAGTCTAGGGATTAACTTCCTGTATGCTGC
			AGGGATTAACT		AAAGAA		CTCATGAACTTGGC		AACTCATGAACTTGGCCATTCTTTGGGTATGGGAC

MMP9	NM_004994	1569	GAGAACCAATCTC	1570	CACCCGAGTGTAACC	1571	ACAGGTATTCCTCT	1572	GAGAACCAATCTCACCGACAGGCAGCTGGCAGAGGA
							GCCAGC

MPPED2	NM_001584	1573	CCGACCAACCCTC	1574	AGGGCATTTAGAGCT	1575	ATTTGACCTTCCAA	1576	CCGACCAACCCTCCAATTATATTTGACCTTCCAAACC
							ACCCAC

MRC1	NM_002438	1577	CTTGACCTCAGGA	1578	GGACTGCGGTCACTC	1579	CCAACCGCTGTTGA	1580	CTTGACCTCAGGACTCTGGATTGGACTTAACAGTCTG
							AGCTCA

MRPL13	NM_014078	1581	TCCGGTTCCCTTCG	1582	GTGGAAAAACTGCGG	1583	CGGCTGGAAATTAT	1584	TCCGGTTCCCTTCGTTTAGGTCGGCTGGAAATTATGT
							GTCCTC

MSH2	NM_000251	1585	GATGCAGAATTGA	1586	TCTTGGCAAGTCGGT	1587	CAAGAAGATTTACT	1588	GATGCAGAATTGAGGCAGACTTTACAAGAAGATTTA
							TCGTCG

MSH3	NM_002439	1589	TGATTACCATCATGG	1590	CTTGTGAAAATGCCAT	1591	TCCCAATTGTCGCT	1592	TGATTACCATCATGGCTCAGATTGGCTCCTATGTTCCTG
			CTCAGA		CCAC		TCTTCTGCAG		CAGAAGAAGCGACAATTGGGATTGTGGATGGCAT

MSH6	NM_000179	1593	TCTATTGGGGGAT	1594	CAAATTGCGAGTGGT	1595	CCGTTACCAGCTGG	1596	TCTATTGGGGGATTGGTAGGAACCGTTACCAGCTGG
							AAATTC

MTA1	NM_004689	1597	CCGCCCTCACCTGAA	1598	GGAATAAGTTAGCCGC	1599	CCCAGTGTCCGCCA	1600	CCGCCCTCACCTGCAGAGAAACGCGCTCCTTGGCGGACA
			GAGA		GCTTCT		AGGAGCG		CTGGGGGAGGAGAGGAAGAAGCGCGGCTAACTT

MTPN	NM_145808	1601	GGTGGAAGGAAAC	1602	CAGCAGCAGAAATTC	1603	AAGCTGCCCACAAT	1604	GGTGGAAGGAAACCTCTTCATTATGCAGCAGATTGT
							CTGCTG

MTSS1	NM_014751	1605	TTCGACAAGTCCT	1606	CTTGGAACATCCGTC	1607	CCAAGAAACAGCGA	1608	TTCGACAAGTCCTCCACCATTCCAAGAAACAGCGAC
							CATCA

MUC1	NM_002456	1609	GGCCAGGATCTGTGG	1610	CTCCACGTCGTGGACA	1611	CTCTGGCCTTCCGA	1612	GGCCAGGATCTGTGGTGGTACAATTGACTCTGGCCTTCC
			TGGTA		TTGA		GAAGGTACC		GAGAAGGTACCATCAATGTCCACGACGTGGAG

MVP	NM_017458	1613	ACGAGAACGAGGGCA	1614	GCATGTAGGTGCTTCC	1615	CGCACCTTTCCGGT	1616	ACGAGAACGAGGGCATCTATGTGCAGGATGTCAAGACCG
			TCTATGT		AATCAC		CTTGACATCCT		GAAAGGTGCGCGCTGTGATTGGAAGCACCTACA

MYBL2	NM_002466	1617	GCCGAGATCGCCAAG	1618	CTTTTGATGGTAGAGT	1619	CAGCATTGTCTGTC	1620	GCCGAGATCGCCAAGATGTTGCCAGGGAGGACAGACAAT
			ATG		TCCAGTGATTC		CTCCCTGGCA		GCTGTGAAGAATCACTGGAACTCTACCATCAAA

MYBPC1	NM_002465	1621	CAGCAACCAGGGA	1622	CAGCAGTAAGTGCCT	1623	AAATTCGCAAGCCC	1624	CAGCAACCAGGGAGTCTGTACCCTGGAAATTCGCAA
							AGCCCC

MYC	NM_002467	1625	TCCCTCCACTCGGAA	1626	CGGTTGTTGCTGATCT	1627	TCTGACACTGTCCA	1628	TCCCTCCACTCGGAAGGACTATCCTGCTGCCAAGAGGGT
			GGACTA		GTCTCA		ACTTGACCCTCTT		CAAGTTGGACAGTGTCAGAGTCCTGAGACAGAT

MYLK3	NM_182493	1629	CACCTGACTGAGCTG	1630	GATGTAGTGCTGGTGC	1631	CACACCCTCACAGA	1632	CACCTGACTGAGCTGGATGTGGTCCTGTTCACCAGGCAG
			GATGT		AGGT		TCTGCCTGGT		ATCTGTGAGGGTGTGCATTACCTGCACCAGCACT

MYO6	NM_004999	1633	AAGCAGTTCTGGA	1634	GATGAGCTCGGCTTC	1635	CAATCCTCAGGGCC	1636	AAGCAGTTCTGGAGCAGGAGCGCAGGGACCGGGAGC
							AGCTCC

NCAM1	NM_000615	1637	TAGTTCCCAGCTG	1638	CAGCCTTGTTCTCAGC	1639	CTCAGCCTCGTCGT	1640	TAGTTCCCAGCTGACCATCAAAAAGGTGGATAAGAA
							TCTTAT

NCAPD3	NM_015261	1641	TCGTTGCTTAGAC	1642	CTCCAGACAGTGTGC	1643	CTACTGTCCGCAGC	1644	TCGTTGCTTAGACAAGGCGCCTACTGTCCGCAGCAA
							AAGGCA

NCOR1	NM_006311	1645	AACCGTTACAGCC	1646	TCTGGAGAGACCCTT	1647	CCAGGCTCAGTCTG	1648	AACCGTTACAGCCCAGAATCCCAGGCTCAGTCTGTCC
							TCCATC

NCOR2	NM_006312	1649	CGTCATCTACGAA	1650	GAGCACTGGGTCACA	1651	CCTCATAGGACAAG	1652	CGTCATCTACGAAGGCAAGAAGGGCCACGTCTTGTC
							ACGTGG

NDRG1	NM_006096	1653	AGGGCAACATTCC	1654	CAGTGCTCCTACTCC	1655	CTGCAAGGACACTC	1656	AGGGCAACATTCCACAGCTGCCCTGGCTGTGATGAG
							ATCACA

NDUFS5	NM_004552	1657	AGAAGAGTCAAGG	1658	AGGCCGAACCTTTTC	1659	TGTCCAAGAAAGGC	1660	AGAAGAGTCAAGGGCACGAGCATCGGGTAGCCATGC
							ATGGCT

NEK2	NM_002497	1661	GTGAGGCAGCGCGAC	1662	TGCCAATGGTGTACAA	1663	TGCCTTCCCGGGCT	1664	GTGAGGCAGCGCGACTCTGGCGACTGGCCGGCCATGCCT
			TCT		CACTTCA		GAGGACT		TCCCGGGCTGAGGACTATGAAGTGTTGTACACC

NETO2	NM_018092	1665	CCAGGGCACCATA	1666	AACGGTAAATCAAGG	1667	AGCCAACCCTTTTC	1668	CCAGGGCACCATACTGTTTCCAGCAGCCAACCCTTTT
							TCCCAT

NEXN	NM_144573	1669	AGGAGGAGGAAGA	1670	GAGCTCCTGATCTGG	1671	TCATCTTCAGCAGT	1672	AGGAGGAGGAAGAAGGTAGCATCATGAATGGCTCCA
							GGAGCC

NFAT5	NM_006599	1673	CTGAACCCCTCTC	1674	AGGAAACGATGGCGA	1675	CGAGAATCAGTCCC	1676	CTGAACCCCTCTCCTGGTCACCGAGAATCAGTCCCCG
							CGTGGA

NFATC2	NM_173091	1677	CAGTCAAGGTCAG	1678	CTTTGGCTCGTGGCAT	1679	CGGGTTCCTACCCC	1680	CAGTCAAGGTCAGAGGCTGAGCCCGGGTTCCTACCC
							ACAGTC

NFKB1	NM_003998	1681	CAGACCAAGGAGA	1682	AGCTGCCAGTGCTAT	1683	AAGCTGTAAACATG	1684	CAGACCAAGGAGATGGACCTCAGCGTGGTGCGGCTC
							AGCCGC

NFKBIA	NM_020529	1685	C TACTGGACGACC	1686	CCTTGACCATCTGCTC	1687	CTCGTCTTTCATGG	1688	CTACTGGACGACCGCCACGACAGCGGCCTGGACTCC
							AGTCCA

NME1	NM_000269	1689	CCAACCCTGCAGACT	1690	ATGTATAATGTTCCTG	1691	CCTGGGACCATCCG	1692	CCAACCCTGCAGACTCCAAGCCTGGGACCATCCGTGGAG
			CCAA		CCAACTTGTATG		TGGAGACTTCT		ACTTCTGCATACAAGTTGGCAGGAACATTATAC

NNMT	NM_006169	1693	CCTAGGGCAGGGA	1694	CTAGTCCAGCCAAAC	1695	CCCTCTCCTCATGC	1696	CCTAGGGCAGGGATGGAGAGAGAGTCTGGGCATGAG
							CCAGAC

NOS3	NM_000603	1697	ATCTCCGCCTCGC	1698	TCGGAGCCATACAGG	1699	TTCACTCGCTTCGC	1700	ATCTCCGCCTCGCTCATGGGCACGGTGATGGCGAAG
							CATCAC

NOX4	NM_016931	1701	CCTCAACTGCAGCCT	1702	TGCTTGGAACCTTCTG	1703	CCGAACACTCTTGG	1704	CCTCAACTGCAGCCTTATCCTTTTACCCATGTGCCGAAC
			TATCC		TGAT		CTTACCTCCG		ACTCTTGGCTTACCTCCGAGGATCACAGAAGGTTC

NPBWR1	NM_005285	1705	TCACCAACCTGTT	1706	GATGTTGATGGGCAG	1707	ATCGCCGACGAGCT	1708	TCACCAACCTGTTCATCCTCAACCTGGCCATCGCCGA
							CTTCAC

NPM1	NM_002520	1709	AATGTTGTCCAGGTT	1710	CAAGCAAAGGGTGGAG	1711	AACAGGCATTTTGG	1712	AATGTTGTCCAGGTTCTATTGCCAAGAATGTGTTGTCCA
			CTATTGC		TTC		ACAACACATTCTTG		AAATGCCTGTTTAGTTTTTAAAGATGGAACTCCAC

NRG1	NM_013957	1713	CGAGACTCTCCTCAT
			AGTGAAAGGTA	1714	CTTGGCGTGTGGAAAT	1715	ATGACCACCCCGGC	1716	CGAGACTCTCCTCATAGTGAAAGGTATGTGTCAGCCATG
					CTACAG		TCGTATGTCA		ACCACCCCGGCTCGTATGTCACCTGTAGATTTCC

NRIP3	NM_020645	1717	CCCACAAGCATGA	1718	TGCTCAATCTGGCCC	1719	AGCTTTCTCTACCC	1720	CCCACAAGCATGAAGGAGAAAAGCTTTCTCTACCCC
							CGGCAT

NRP1	NM_003873	1721	CAGCTCTCTCCACGC	1722	CCCAGCAGCTCCATTC	1723	CAGGATCTACCCCG	1724	CAGCTCTCTCCACGCGATTCATCAGGATCTACCCCGAGA
			GATTC		TGA		AGAGAGCCACTCAT		GAGCCACTCATGGCGGACTGGGGCTCAGAATGGA

NUP62	NM_153719	1725	AGCCTCTTTGCGTCA	1726	CTGTGGTCACAGGGGT	1727	TCATCTGCCACCAC	1728	AGCCTCTTTGCGTCAATAGCAACTGCTCCAACCTCATCT
			ATAGC		ACAG		TGGACTCTCC		GCCACCACTGGACTCTCCCTCTGTACCCCTGTGAC

OAZ1	NM_004152	1729	AGCAAGGACAGCT	1730	GAAGACATGGTCGGC	1731	CTGCTCCTCAGCGA	1732	AGCAAGGACAGCTTTGCAGTTCTCCTGGAGTTCGCTG
							ACTCCA

OCLN	NM_002538	1733	CCCTCCCATCCGA	1734	GACGCGGGAGTGTAG	1735	CTCCTCCCTCGGTG	1736	CCCTCCCATCCGAGTTTCAGGTGAATTGGTCACCGAG
							ACCAAT

ODC1	NM_002539	1737	AGAGATCACCGGCGT	1738	CGGGCTCAGCTATGAT	1739	CCAGCGTTGGACAA	1740	AGAGATCACCGGCGTAATCAACCCAGCGTTGGACAAATA
			AATCAA		TCTCA		ATACTTTCCGTCA		CTTTCCGTCAGACTCTGGAGTGAGAATCATAGCT

OLFML2	NM_015441	1741	CATGTTGGAAGGA	1742	CACCAGTTTGGTGGT	1743	TGGCCTGGATCTCC	1744	CATGTTGGAAGGAGCGTTCTATGGCCTGGATCTCCTG
							TGAAGC

OLFML3	NM_020190	1745	TCAGAACTGAGGC	1746	CCAGATAGTCTACCT	1747	CAGACGATCCACTC	1748	TCAGAACTGAGGCCGACACCATCTCCGGGAGAGTGG
							TCCCGG

OMD	NM_005014	1749	CGCAAACTCAAGACT	1750	CAGTCACAGCCTCAAT	1751	TCCGATGCACATTC	1752	CGCAAACTCAAGACTATCCCAAATATTCCGATGCACATT
			ATCCCA		TTCATT		AGCAACTCTACC		CAGCAACTCTACCTTCAGTTCAATGAAATTGAGG

OR51E1	NM_152430	1753	GCATGCTTTCAGG	1754	AGAAGATGGCCAGCA	1755	TCCTCATCTCCACC	1756	GCATGCTTTCAGGCATTGACATCCTCATCTCCACCTC
							TCATCC

OR51E2	NM_030774	1757	TATGGTGCCAAAA	1758	GTCCTTGTCACAGCT	1759	ACATAGCCAGCACC	1760	TATGGTGCCAAAACCAAACAGATCAGAACACGGGTG
							CGTGTT

OSM	NM_020530	1761	GTTTCTGAAGGGG	1762	AGGTGTCTGGTTTGG	1763	CTGAGCTGGCCTCC	1764	GTTTCTGAAGGGGAGGTCACAGCCTGAGCTGGCCTC
							TATGCC

PAGE1	NM_003785	1765	CAACCTGACGAAGTG	1766	CAGATGCTCCCTCATC	1767	CCAACTCAAAGTCA	1768	CAACCTGACGAAGTGGAATCACCAACTCAAAGTCAGGAT
			GAATC		CTCT		GGATTCTACACCTG		TCTACACCTGCTGAAGAGAGAGAGGATGAGGGA
							C

PAGE4	NM_007003	1769	GAATCTCAGCAAGAG	1770	GTTCTTCGATCGGAGG	1771	CCAACTGACAATCA	1772	GAATCTCAGCAAGAGGAACCACCAACTGACAATCAGGAT
			GAACCA		TGTT		GGATATTGAACCTG		ATTGAACCTGGACAAGAGAGAGAAGGAACACCT
							G

PAK6	NM_020168	1773	CCTCCAGGTCACC	1774	GTCCCTTCAGGCCAG	1775	AGTTTCAGGAAGGC	1776	CCTCCAGGTCACCCACAGCCAGTTTCAGGAAGGCTG
							TGCCCC

PATE1	NM_138294	1777	TGGTAATCCCTGG	1778	TCCACCTTATGCCTTT	1779	CAGCACAGTTCTTT	1780	TGGTAATCCCTGGTTAACCTTCATGGGCTGCCTAAAG
							AGGCAG

PAC3	NM_015342	1781	CGTGATTGTCAGG	1782	AGAAAGGGGAGATGC	1783	CTGAGATGCTCCCT	1784	CGTGATTGTCAGGAGCAAGACCTGAGATGCTCCCTG
							GCCTTC

PCDHGB	NM_018927	1785	CCCAGCGTTGAAG	1786	GAAACGCCAGTCCGT	1787	ATTCTTAAACAGCA	1788	CCCAGCGTTGAAGCAGATAAGAAGATTCTTAAACAG
							AGCCCC

PCNA	NM_002592	1789	GAAGGTGTTGGAG	1790	GGTTTACACCGCTGG	1791	ATCCCAGCAGGCCT	1792	GAAGGTGTTGGAGGCACTCAAGGACCTCATCAACGA
							CGTTGA

PDE9A	NM_001001570	1793	TTCCACAACTTCCGG	1794	AGACTGCAGAGCCAGA	1795	TACATCATCTGGGC	1796	TTCCACAACTTCCGGCACTGCTTCTGCGTGGCCCAGATG
			CAC		CCA		CACGCAGAAG		ATGTACAGCATGGTCTGGCTCTGCAGTCT

PDGFRB	NM_002609	1797	CCAGCTCTCCTTCC	1798	GGGTGGCTCTCACTT	1799	ATCAATGTCCCTGT	1800	CCAGCTCTCCTTCCAGCTACAGATCAATGTCCCTGTC
							CCGAGT

PECAM1	NM_000442	1801	TGTATTTCAAGACCT	1802	TTAGCCTGAGGAATTG	1803	TTTATGAACCTGCC	1804	TGTATTTCAAGACCTCTGTGCACTTATTTATGAACCTGC
			CTGTGCACTT		CTGTGTT		CTGCTCCCACA		CCTGCTCCCACAGAACACAGCAATTCCTCAGGCT

PEX10	NM_153818	1805	GGAGAAGTTCCCTCC	1806	ATCTGTGTCCAGGCCC	1807	CTACCTTCGGCACT	1808	GGAGAAGTTCCCTCCCCAGAAGCTCATCTACCTTCGGCA
			CCAG		AC		ACCGCTGAGC		CTACCGCTGAGCCGGCGCCCGGGTGGGCCTGGAC

PGD	NM_002631	1809	ATTCCCATGCCCT	1810	CTGGCTGGAAGCATC	1811	ACTGCCCTCTCCTT	1812	ATTCCCATGCCCTGTTTTACCACTGCCCTCTCCTTCT
							CTATGA

PGF	NM_002632	1813	GTGGTTTTCCCTCG	1814	AGCAAGGGAACAGCC	1815	ATCTTCTCAGACGT	1816	GTGGTTTTCCCTCGGAGCCCCCTGGCTCGGGACGTCT
							CCCGAG

PGK1	NM_000291	1817	AGAGCCAGTTGCTGT	1818	CTGGGCCTACACAGTC	1819	TCTCTGCTGGGCAA	1820	AGAGCCAGTTGCTGTAGAACTCAAATCTCTGCTGGGCAA
			AGAACTCAA		CTTCA		GGATGTTCTGTTC		GGATGTTCTGTTCTTGAAGGACTGTGTAGGCCCA

PGR	NM_000926	1821	GATAAAGGAGCCG	1822	TCACAAGTCCGGCAC	1823	TAAATTGCCGTCGC	1824	GATAAAGGAGCCGCGTGTCACTAAATTGCCGTCGCA
							AGCCGC

PHTF2	NM_020432	1825	GATATGGCTGATG	1826	GGTTTGGGTGTTCTTG	1827	ACAATCTGGCAATG	1828	GATATGGCTGATGCTGCTCCTGGGAACTGTGCATTGC
							CACAGT

PIK3C2A	NM_002645	1829	ATACCAATCACCGCA	1830	CACACTAGCATTTCTC	1831	TGTGCTGTGACTGG	1832	ATACCAATCACCGCACAAACCCAGGCTATTTGTTAAGTC
			CAAACC		CGCATA		ACTTAACAAATAGC		CAGTCACAGCACAAAGAAACATATGCGGAGAAAA
							CT

PIK3CA	NM_006218	1833	GTGATTGAAGAGC	1834	GTCCTGCGTGGGAAT	1835	TCCTGCTTCTCGGG	1836	GTGATTGAAGAGCATGCCAATTGGTCTGTATCCCGA
							ATACAG

PIK3CG	NM_002649	1837	GGAGAACTCAATG	1838	TGATGCTTAGGCAGG	1839	TTCTGGACAATTAC	1840	GGAGAACTCAATGTCCATCTCCATTCTTCTGGACAAT
							TGCCAC

PIM1	NM_002648	1841	CTGCTCAAGGACA	1842	GGATCCACTCTGGAG	1843	TACACTCGGGTCCC	1844	CTGCTCAAGGACACCGTCTACACGGACTTCGATGGG
							ATCGAA

PLA2G7	NM_005084	1845	CCTGGCTGTGGTT	1846	TGACCCATGCTGATG	1847	TGGCAATACATAAA	1848	CCTGGCTGTGGTTTATCCTTTTGACTGGCAATACATA
							TCCTGT

PLAU	NM_002658	1849	GTGGATGTGCCCT	1850	CTGCGGATCCAGGGT	1851	AAGCCAGGCGTCTA	1852	GTGGATGTGCCCTGAAGGACAAGCCAGGCGTCTACA
							CACGAG

PLAUR	NM_002659	1853	CCCATGGATGCTC	1854	CCGGTGGCTACCAGA	1855	CATTGACTGCCGAG	1856	CCCATGGATGCTCCTCTGAAGAGACTTTCCTCATTGA
							GCCCCA

PLG	NM_000301	1857	GGCAAAATTTCCA	1858	ATGTATCCATGAGCG	1859	TGCCAGGCCTGGGA	1860	GGCAAAATTTCCAAGACCATGTCTGGACTGGAATGC
							CTCTCA

PLK1	NM_005030	1861	AATGAATACAGTATT	1862	TGTCTGAAGCATCTTC	1863	AACCCCGTGGCCGC	1864	AATGAATACAGTATTCCCAAGCACATCAACCCCGTGGCC
			CCCAAGCACAT		TGGATGA		CTCC		GCCTCCCTCATCCAGAAGATGCTTCAGACA

PLOD2	NM_000935	1865	CAGGGAGGTGGTTGC	1866	TCTCCCAGGATGCATG	1867	TCCAGCCTTTTCGT	1868	CAGGGAGGTGGTTGCAAATTTCTAAGGTACAATTGCTCT
			AAAT		AAG		GGTGACTCAA		ATTGAGTCACCACGAAAAGGCTGGAGCTTCATG

PLP2	NM_002668	1869	CCTGATCTGCTTCA	1870	GCAGCAAGGATCATC	1871	ACACCAGGCTACTC	1872	CCTGATCTGCTTCAGTGCCTCCACACCAGGCTACTCC
							CTCCCT

PNLIPRP	NM_005396	1873	TGGAGAAGGTGAA	1874	CACGGCTTGGGTGTA	1875	ACCCGTGCCTCCAG	1876	TGGAGAAGGTGAACTGCATCTGTGTGGACTGGAGGC
							TCCACA

POSTN	NM_006475	1877	GTGGCCCAATTAG	1878	TCACAGGTGCCAGCA	1879	TTCTCCATCTGGCC	1880	GTGGCCCAATTAGGCTTGGCATCTGCTCTGAGGCCA
							TCAGAG

PPAP2B	NM_003713	1881	ACAAGCACCATCC	1882	CACGAAGAAAACTAT	1883	ACCAGGGCTCCTTG	1884	ACAAGCACCATCCCAGTGATGTTCTGGCAGGATTTGC
							AGCAAA

PPFIA3	NM_003660	1885	CCTGGAGCTCCGT	1886	AGCCACATAGGGATC	1887	CACCCACTTTACCT	1888	CCTGGAGCTCCGTTACTCTCAGGCACCCACTTTACCT
							TCTGGT

PP1R12A	NM_002480	1889	CGGCAAGGGGTTGAT	1890	TGCCTGGCATCTCTAA	1891	CCGTTCTTCTTCCT	1892	CGGCAAGGGGTTGATATAGAAGCAGCTCGAAAGGAAGAA
			ATAGA		GCA		TTCGAGCTGC		GAACGGATCATGCTTAGAGATGCCAGGCA

PPP3CA	NM_000944	1893	ATACTCCGAGCCC	1894	GGAAGCCTGTTGTTT	1895	TACATGCGGTACCC	1896	ATACTCCGAGCCCACGAAGCCCAAGATGCAGGGTAC
							TGCATC

PRIMA1	NM_178013	1897	ATCCTCTTCCCTGA	1898	CCCAGCTGAGAGGGA	1899	TGACGCATCCAGGG	1900	ATCCTCTTCCCTGAGCCGCTGACGCATCCAGGGCTCT
							CTCTAG

PRKAR1	NM_002735	1901	ACAAAACCATGAC	1902	TGTCATCCAGGTGAG	1903	AAGGCCATCTCCAA	1904	ACAAAACCATGACTGCGCTGGCCAAGGCCATCTCCA
							GAACGT

PRKAR2B	NM_002736	1905	TGATAATCGTGGGAG	1906	GCACCAGGAGAGGTAG	1907	CGAACTGGCCTTAA	1908	TGATAATCGTGGGAGTTTCGGCGAACTGGCCTTAATGTA
			TTTCG		CAGT		TGTACAATACACCC		CAATACACCCAGAGCAGCTACAATCACTGCTAC
							A

PRKCA	NM_002737	1909	CAAGCAATGCGTC	1910	GTAAATCCGCCCCCT	1911	CAGCCTCTGCGGAA	1912	CAAGCAATGCGTCATCAATGTCCCCAGCCTCTGCGG
							TGGATC

PRKCB	NM_002738	1913	GACCCAGCTCCAC	1914	CCCATTCACGTACTCC	1915	CCAGACCATGGGAC	1916	GACCCAGCTCCACTCCTGCTTCCAGACCATGGACCGC
							CGCCTGT

PROM1	NM_006017	1917	CTATGACAGGCAT	1918	CTCCAACCATGAGGA	1919	ACCCGAGGCTGTGT	1920	CTATGACAGGCATGCCACCCCGACCACCCGAGGCTG
							CTCCAA

PROS1	NM_000313	1921	GCAGCACAGGAAT	1922	CCCACCTATCCAACCT	1923	CTCATCCTGACAGA	1924	GCAGCACAGGAATCTTCTTCTTGGCAGCTGCAGTCTG
							CTGCAG

PSCA	NM_005672	1925	ACCGTCATCAGCAAA	1926	CGTGATGTTCTTCTTG	1927	CCTGTGAGTCATCC	1928	ACCGTCATCAGCAAAGGCTGCAGCTTGAACTGCGTGGAT
			GGCT		CCC		ACGCAGTTCA		GACTCACAGGACTACTACGTGGGCAAGAAGAAC

PSMD13	NM_002817	1929	GGAGGAGCTCTACAC	1930	CGGATCCTGCACAAAA	1931	CCTGAAGTGTCAGC	1932	GGAGGAGCTCTACACGAAGAAGTTGTGGCATCAGCTGAC
			GAAGAAG		TCA		TGATGCCACA		ACTTCAGGTGCTTGATTTTGTGCAGGATCCG

PTCH1	NM_000264	1933	CCACGACAAAGCC	1934	TACTCGATGGGCTCT	1935	CCTGAAACAAGGCT	1936	CCACGACAAAGCCGACTACATGCCTGAAACAAGGCT
							GAGAAT

PTEN	NM_000314	1937	TGGCTAAGTGAAGAT	1938	TGCACATATCATTAC	1939	CCTTTCCAGCTTTA	1940	TGGCTAAGTGAAGATGACAATCATGTTGCAGCAATTCAC
			GACAATCATG		ACCAGTTCGT		CAGTGAATTGCTGC		TGTAAAGCTGGAAAGGGACGAACTGGTGTAATG
							A

PTGER3	NM_000957	1941	TAACTGGGGCAAC	1942	TTGCAGGAAAAGGTG	1943	CCTTTGCCTTCCTG	1944	TAACTGGGGCAACTTTTCTTCGCCTCTGCCTTTGCC
							GGGCTC

PTGS2	NM_000963	1945	GAATCATTCACCAGG	1946	CTGTACTGCGGGTGGA	1947	CCTACCACCAGCAA	1948	GAATCATTCACCAGGCAAATTGCTGGCAGGGTTGCTGGT
			CAAATTG		ACAT		CCCTGCCA		GGTAGGAATGTTCCACCCGCAGTACAG

PTH1R	NM_000316	1949	CGAGGTACAAGCTGA	1950	GCGTGCCTTTCGCTTG	1951	CCAGTGCCAGTGTC	1952	CGAGGTACAAGCTGAGATCAAGAAATCTTGGAGCCGCTG
			GATCAAGAA		AA		CAGCGGCT		GACACTGGCACTGGACTTCAAGCGAAAGGCACG

PTHLH	NM_002820	1953	AGTGACTGGGAGTGG	1954	AAGCCTGTTACCGTGA	1955	TGACACCTCCACAA	1956	AGTGACTGGGAGTGGGCTAGAAGGGGACCACCTGTCTGA
			GCTAGAA		ATCGA		CGTCGCTGGA		CACCTCCACAACGTCGCTGGAGCTCGATTCACG

PTK2	NM_005607	1957	GACCGGTCGAATG	1958	CTGGACATCTCGATG	1959	ACCAGGCCCGTCAC	1960	GACCGGTCGAATGATAAGGTGTACGAGAATGTGACG
							ATTCTC

PTK2B	NM_004103	1961	CAAGCCCAGCCGA	1962	GAACCTGGAACTGCA	1963	CTCCGCAAACCAAC	1964	CAAGCCCAGCCGACCTAAGTACAGACCCCCTCCGCA
							CTCCTG

PTK6	NM_005975	1965	GTGCAGGAAAGGTTC	1966	GCACACACGATGGAGT	1967	AGTGTCTGCGTCCA	1968	GTGCAGGAAAGGTTCACAAATGTGGAGTGTCTGCGTCCA
			ACAAA		AAGG		ATACACGCGT		ATACACGCGTGTGCTCCTCTCCTTACTCCATCGT

PTK7	NM_002821	1969	TCAGAGGACTCAC	1970	CATACACCTCCACGC	1971	CGCAAGGTCCCATT	1972	TCAGAGGACTCACGGTTCGAGGTCTTCAAGAATGGG
							CTTGAA

PTPN1	NM_002827	1973	AATGAGGAAGTTT	1974	CTTCGATCACAGCCA	1975	CTGATCCAGACAGC	1976	AATGAGGAAGTTTCGGATGGGGCTGATCCAGACAGC
							CGACCA

PTPRK	NM_002844	1977	TCAAACCCTCCCA	1978	AGCAGCCAGTTCGTC	1979	CCCCATCGTTGTAC	1980	TCAAACCCTCCCAGTGCTGGCCCCATCGTTGTACATT
							ATTGCA

PTTG1	NM_004219	1981	GGCTACTCTGATCTA	1982	GCTTCAGCCCATCCTT	1983	CACACGGGTGCCTG	1984	GGCTACTCTGATCTATGTTGATAAGGAAAATGGAGAACC
			TGTTGATAAGG		AGCA		GTTCTCCA		AGGCACCCGTGTGGTTGCTAAGGATGGGCTGAA

PYCARD	NM_013258	1985	CTTTATAGACCAG	1986	AGCATCCAGCAGCCA	1987	ACGTTTGTGACCCT	1988	CTTTATAGACCAGCACCGGGCTGCGCTTATCGGCGAG
							CGCGAT

RAB27A	NM_004580	1989	TGAGAGATTAATG	1990	CCGGATGCTTTATTCG	1991	ACAAATTGCTTCTC	1992	TGAGAGATTAATGGGCATTGTGTACAAATTGCTTCTC
							ACCATC

RAB30	NM_014488	1993	TAAAGGCTGAGGC	1994	CTCCCCAGCATCTCAT	1995	CCATCAGGGCAGTT	1996	TAAAGGCTGAGGCACGGAGAAGAAAAGGAATCAGCA
							GCTGAT

RAB31	NM_006868	1997	CTGAAGGACCCTA	1998	ATGCAAAGCCAGTGT	1999	CTTCTCAAAGTGAG	2000	CTGAAGGACCCTACGCTCGGTGGCCTGGCACCTCAC
							GTGCCA

RAD21	NM_006265	2001	TAGGGATGGTATCTG	2002	TCGCGTACACCTCTGC	2003	CACTTAAAACGAAT	2004	TAGGGATGGTATCTGAAACAACAATGGTCACCCTCTTGA
			AAACAACA		TC		CTCAAGAGGGTGAC		GATTCGTTTTAAGTGTAATTCCATAATGAGCAGAG
							CA

RAD51	NM_002875	2005	AGACTACTCGGGT	2006	AGCATCCGCAGAAAC	2007	CTTTCAGCCAGGCA	2008	AGACTACTCGGGTCGAGGTGAGCTTTCAGCCAGGCA
							GATGCA

RAD9A	NM_004584	2009	GCCATCTTCACCA	2010	CGGTGTCTGAGAGTG	2011	CTTTGCTGGACGGC	2012	GCCATCTTCACCATCAAGGACTCTTTGCTGGACGGCC
							CACTTT

RAF1	NM_002880	2013	CGTCGTATGCGAG	2014	TGAAGGCGTGAGGTG	2015	TCCAGGATGCCTGT	2016	CGTCGTATGCGAGAGTCTGTTTCCAGGATGCCTGTTA
							TAGTTC

RAGE	NM_014226	2017	ATTAGGGGGACTTT	2018	GGGTGGAGATGTATT	2019	CCGGAGTGTCTATT	2020	ATTAGGGGACTTTGGCTCCTGCCGGAGTGTCTATTCC
							CCAAGC

RALA	NM_005402	2021	TGGTCCTGAATGT	2022	CCCCATTTCACCTCTT	2023	TTGTGTTTCTTGGG	2024	TGGTCCTGAATGTAGCGTGTAAGCTTGTGTTTCTTGG
							CAGTCT

RALBP1	NM_006788	2025	GGTGTCAGATATAAA	2026	TTCGATATTGCCAGCA	2027	TGCTGTCCTGTCGG	2028	GGTGTCAGATATAAATGTGCAAATGCCTTCTTGCTGTCC
			TGTGCAAATGC		GCTATAAA		TCTCAGTACGTTCA		TGTCGGTCTCAGTACGTTCACTTTATAGCTGCTGG

RAP1B	NM_001010942	2029	TGACAGCGTGAGAGG	2030	CTGAGCCAAGAACGAC	2031	CACGCATGATGCAA	2032	TGACAGCGTGAGAGGTACTAGGTTTTGACAAGCTTGCAT
			TACTAGG		TAGCTT		GCTTGTCAAA		CATGCGTGAGTATAAGCTAGTCGTTCTTGGCTCA

RARB	NM_000965	2033	ATGAACCCTTGACCC	2034	GAGCTGGGTGAGATGC	2035	TGTGCTCTGCTGTG	2036	ATGAACCCTTGACCCCAAGTTCAAGTGGGAACACAGCAG
			CAAGT		TAGG		TTCCCACTTG		AGCACAGTCCTAGCATCTCACCCAGCTC

RASSF1	NM_007182	2037	AGGGCACGTGAAGTC	2038	AAAGAGTGCAAACTTG	2039	CACCACCAAGAACT	2040	AGGGCACGTGAAGTCATTGAGGCCCTGCTGCGAAAGTTC
			ATTG		CGG		TTCGCAGCAG		TTGGTGGTGGATGACCCCCGCAAGTTTGCACTCT

RB1	NM_000321	2041	CGAAGCCCTTACA	2042	GGACTCTTCAGGGGT	2043	CCCTTACGGATTCC	2044	CGAAGCCCTTACAAGTTTCCTAGTTCACCCTTACGGA
							TGGAGG

RECK	NM_021111	2045	GTCGCCGAGTGTG	2046	GTGGGATGATGGGTT	2047	TCAAGTGTCCTTCG	2048	GTCGCCGAGTGTGCTTCTGTCAAGTGTCCTTCGCTCT
							CTCTTG

REG4	NM_032044	2049	TGCTAACTCCTGCAC	2050	TGCTAGGTTTCCCCTC	2051	TCCTCTTCCTTTCT	2052	TGCTAACTCCTGCACAGCCCCGTCCTCTTCCTTTCTGCT
			AGCC		TGAA		GCTAGCCTGGC		AGCCTGGCTAAATCTGCTCATTATTTCAGAGGGGA

RELA	NM_021975	2053	CTGCCGGGATGGC	2054	CCAGGTTCTGGAAAC	2055	CTGAGCTCTGCCCG	2056	CTGCCGGGATGGCTTCTATGAGGCTGAGCTCTGCCC
							GACCGC

RFX1	NM_002918	2057	TCCTCTCCAAGTTC	2058	CAGGCCCTGGTACAG	2059	TCCAATGGACCAAG	2060	TCCTCTCCAAGTTCGAGCCCGTGCTCCAATGGACCAA
							CACTGT

RGS10	NM_001005339	2061	AGACATCCACGACAG	2062	CCATTTGGCTGTGCTC	2063	AGTTCCAGCAGCAG	2064	AGACATCCACGACAGCGATGGCAGTTCCAGCAGCAGCCA
			CGAT		TTG		CCACCAGAG		CCAGAGCCTCAAGAGCACAGCCAAATGG

RGS7	NM_002924	2065	CAGGCTGCAGAGAGC	2066	TTTGCTTGTGCTTCTG	2067	TGAAAATGAACTCC	2068	CAGGCTGCAGAGAGCATTTGCCCGGAAGTGGGAGTTCAT
			ATTT		CTTG		CACTTCCGGG		TTTCATGCAAGCAGAAGCACAAGCAAA

RHOA	NM_001664	2069	TGGCATAGCTCTG	2070	TGCCACAGCTGCATG	2071	AAATGGGCTCAACC	2072	TGGCATAGCTCTGGGGTGGGCAGTTTTTTGAAAATG
							AGAAA

RHOB	NM_004040	2073	AAGCATGAACAGG	2074	CCTCCCCAAGTCAGT	2075	CTTTCCAACCCCTG	2076	AAGCATGAACAGGACTTGACCATCTTTCCAACCCCTG
							GGGAAG

RHOC	NM_175744	2077	CCCGTTCGGTCTG	2078	GAGCACTCAAGGTAG	2079	TCCGGTTCGCCATG	2080	CCCGTTCGGTCTGAGGAAGGCCGGGACATGGCGAAC
							TCCCG

RLN1	NM_006911	2081	AGCTGAAGGCAGCCC	2082	TTGGAATCCTTTAATG	2083	TGAGAGGCAACCAT	2084	AGCTGAAGGCAGCCCTATCTGAGAGGCAACCATCATTAC
			TATC		CAGGT		CATTACCAGAGC		CAGAGCTACAGCAGTATGTACCTGCATTAAAGG

RND3	NM_005168	2085	TCGGAATTGGACT	2086	CTGGTTACTCCCCTCC	2087	TTTTAAGCCTGACT	2088	TCGGAATTGGACTTGGGAGGCGCGGTGAGGAGTCAG
							CCTCAC

RNF114	NM_018683	2089	TGACAGGGGAAGT	2090	GGAAGACAGCTTTGG	2091	CCAGGTCAGCCCTT	2092	TGACAGGGGAAGTGGGTCCCCAGGTCAGCCCCTTCTC
							CTCTTC

ROBO2	NM_002942	2093	CTACAAGGCCCAG	2094	CACCAGTGGCTTTAC	2095	CTGTACCATCCACT	2096	CTACAAGGCCCAGCCAACCAAACGCTGGCAGTGGAT
							GCCAGC

RRM1	NM_001033	2097	GGGCTACTGGCAG	2098	CTCTCAGCATCGGTA	2099	CATTGGAATTGCCA	2100	GGGCTACTGGCAGCTACATTGCTGGGACTAATGGCA
							TTAGTC

RRM2	NM_001034	2101	CAGCGGGATTAAA	2102	ATCTGCGTTGAAGCA	2103	CCAGCACAGCCAGT	2104	CAGCGGGATTAAACAGTCCTTTAACCAGCACAGCCA
							TAAAAG

S100P	NM_005980	2105	AGACAAGGATGCC	2106	GAAGTCCACCTGGGC	2107	TTGCTCAAGGACCT	2108	AGACAAGGATGCCGTGGATAAATTGCTCAAGGACCT
							GGACGC

SAT1	NM_002970	2109	CCTTTTACCACTGC	2110	ACAATGCTGTGTCCTT	2111	TCCAGTGCTCTTTC	2112	CCTTTTACCACTGCCTGGTTGCGAAGTGCCGAAAGA
							GGCACT

SCUBE2	NM_020974	2113	TGACAATCAGCACAC	2114	TGTGACTACAGCCGTG	2115	CAGGCCCTCTTCCG	2116	TGACAATCAGCACACCTGCATTCACCGCTCGGAAGAGGG
			CTGCAT		ATCCTTA		AGCGGT		CCTGAGCTGCATGAATAAGGATCACGGCTGTAG

SDC1	NM_002997	2117	GAAATTGACGAGG	2118	AGGAGCTAACGGAGA	2119	CTCTGAGCGCCTCC	2120	GAAATTGACGAGGGGTGTCTTGGGCAGAGCTGGCTC
							ATCCAA

SDC2	NM_002998	2121	GGATTGAAGTGGC	2122	ACCAGCCACAGTACC	2123	AACTCCATCTCCTT	2124	GGATTGAAGTGGCTGGAAAGAGTGATGCCTGGGGAA
							CCCCAG

SDHC	NM_003001	2125	CTTCCCTCGGGTCT	2126	TTCCCTCCTGGTAAA	2127	TTACATCCTCCCTC	2128	CTTCCCTCGGGTCTCAGGCATTTACATCCTCCCTCTC
							TCCCCG

SEC14L1	NM_001039573	2129	AGGGTTCCCATGTGA	2130	GCAGGCATGCTGTGGA	2131	CGGGCTTCTACATC	2132	AGGGTTCCCATGTGACCAGGTGGCCGGGCTTCTACATCC
			CCAG		AT		CTGCAGTGG		TGCAGTGGAAATTCCACAGCATGCCTGC

SEC23A	NM_006364	2133	CGTGTGCATTAGA	2134	CCCATTACCATGTATC	2135	TCCTGGAGATGAAA	2136	CGTGTGCATTAGATCAGACAGGTCTCCTGGAGATGA
							TGCTGT

SEMA3A	NM_006080	2137	TTGGAATGCAGTC	2138	CTCTTCATTTCGCCTC	2139	TTGCCAATAGACCA	2140	TTGGAATGCAGTCCGAAGTCGCAGAGAGCGCTGGTC
							GCGCTC

SEPT9	NM_006640	2141	CAGTGACCACGAG	2142	CTTCGATGGTACCCC	2143	TTGCCAATAGACCA	2144	CAGTGACCACGAGTACCAGGTCAACGGCAAGAGGAT
							GCGCTC

SERPINA3	NM_001085	2145	GTGTGGCCCTGTCTG	2146	CCCTGTGCATGTGAGA	2147	AGGGAATCGCTGTC	2148	GTGTGGCCCTGTCTGCTTATCCTTGGAAGGTGACAGCGA
			CTTA		GCTAC		ACCTTCCAAG		TTCCCTGTGTAGCTCTCACATGCACAGGG

SERPINB5	NM_002639	2149	CAGATGGCCACTTTG	2150	GGCAGCATTAACCACA	2151	AGCTGACAACAGTG	2152	CAGATGGCCACTTTGAGAACATTTTAGCTGACAACAGTG
			AGAACATT		AGGATT		TGAACGACCAGACC		TGAACGACCAGACCAAAATCCTTGTGGTTAATG

SESN3	NM_144665	2153	GACCCTGGTTTTG	2154	GAGCTCGGAATGTTG	2155	TGCTCTTCTCCTCG	2156	GACCCTGGTTTTGGGTATGAAGACTTTGCCAGACGA
							TCTGGC

SFRP4	NM_003014	2157	TACAGGATGAGGC	2158	GTTGTTAGGGCAAGG	2159	CCTGGGACAGCCTA	2160	TACAGGATGAGGCTGGGCATTGCCTGGGACAGCCTA
							TGTAAG

SH3RF2	NM_152550	2161	CCATCACAACAGCCT	2162	CACTGGGGTGCTGATC	2163	AACCGGATGGTCCA	2164	CCATACAACAGCCTTGAACACTCTCAACCGGATGGTCCA
			TGAAC		TCTA		TTCTCCTTCA		TTCTCCTTCAGGGCGCCATATGGTAGAGATCAG

SH3YL1	NM_015677	2165	CCTCCAAAGCCAT	2166	CTTTGAGAGCCAGAG	2167	CACAGCAGTCATCT	2168	CCTCCAAAGCCATTGTCAAGACCACAGCAGTCATCT
							GCACCA

SHH	NM_000193	2169	GTCCAAGGCACAT	2170	GAAGCAGCCTCCCGA	2171	CACCGAGTTCTCTG	2172	GTCCAAGGCACATATCCACTGCTCGGTGAAAGCAGA
							CTTTCA

SHMT2	NM_005412	2173	AGCGGGTGCTAGA	2174	ATGGCACTTCGGTCT	2175	CCATCACTGCCAAC	2176	AGCGGGTGCTAGAGCTTGTATCCATCACTGCCAACA
							AAGAAC

SIM2	NM_005069	2177	GATGGTAGGAAGG	2178	CACAAGGAGCTGTGA	2179	CGCCTCTCCACGCA	2180	GATGGTAGGAAGGGATGTGCCCGCCTCTCCACGCAC
							CTCAGC

SIPA1L1	NM_015556	2181	CTAGGACAGCTTG	2182	CATAACCGTAGGGCT	2183	CGCCACAATGCCCT	2184	CTAGGACAGCTTGGCTTCCATGTCAACTATGAGGGC
							CATAGT

SKIL	NM_005414	2185	AGAGGCTGAATAT	2186	CTATCGGCCTCAGCA	2187	CCAATCTCTGCCTC	2188	AGAGGCTGAATATGCAGGACAGTTGGCAGAACTGAG
							AGTTCT

SLC22A3	NM_021977	2189	ATCGTCAGCGAGT	2190	CAGGATGGCTTGGGT	2191	CAGCATCCACGCAT	2192	ATCGTCAGCGAGTTTGACCTTGTCTGTGTCAATGCGT
							TGACAC

SLC25A21	NM_030631	2193	AAGTGTTTTTCCCCC	2194	GGCCGATCGATAGTCT	2195	TCATGGTGCTGCAT	2196	AAGTGTTTTTCCCCCTTGAGATAATGGATATTTGCTATG
			TTGAGAT		CTCTT		AGCAAATATCCA		CAGCACCATGAAGAAGAGAGACTATCGATCGGCC

SLC44A1	NM_080546	2197	AGGACCGTAGCTG	2198	ATCCCATCCCAATGC	2199	TACCATGGCTGCTG	2200	AGGACCGTAGCTGCACAGACATACCATGGCTGCTGC
							CTCTTC

SMAD4	NM_005359	2201	GGACATTACTGGC	2202	ACCAATACTCAGGAG	2203	TGCATTCCAGCCTC	2204	GGACATTACTGGCCTGTTCACAATGAGCTTGCATTCC
							CCATTT

SMARCC2	NM_003075	2205	TACCGACTGAACCCC	2206	GACATCACCCGCTAGG	2207	TATCTTACCTCTAC	2208	TACCGACTGAACCCCCAAGAAGTATCTTACCTCTACCGC
			CAA		TTTC		CGCCTGCCGC		CTGCCGCCGAAACCTAGCGGGTGATGTC

SMARCD1	NM_003076	2209	CCGAGTTAGCATATC	2210	CCTTTGTGCCCAGCTG	2211	CCCACCCTTGCTGT	2212	CCGAGTTAGACATATCCCAGGCTCGCAGACTCAACACAG
			CCAGG		TC		GTTGAGTCTG		CAAGGGTGGGAGACAGCTGGGCACAAAGG

SMO	NM_005631	2213	GGCATCCAGTGCC	2214	CGCGATGTAGCTGTG	2215	CTTCACAGAGGCTG	2216	GGCATCCAGTGCCAGAACCCGCTCTTCACAGAGGCT
							AGCACC

SNA11	NM_005985	2217	CCCAATCGGAAGC	2218	GTAGGGCTGCTGGAA	2219	TCTGGATTAGAGTC	2220	CCCAATCGGAAGCCTAACTACAGCGAGCTGCAGGAC
							CTGCAG

SNRPB2	NM_003092	2221	CGTTTCCTGCTTTT	2222	AGGTAGAAGGCGCAC	2223	CCCACCTAAGGCCT	2224	CGTTTCCTGCTTTTGGTTCTTACAGTAGTCGGCGTAG
							ACGCCG

SOD1	NM_000454	2225	TGAAGAGAGGCAT	2226	AATAGACACATCGGC	2227	TTTGTCAGCAGTCA	2228	TGAAGAGAGGCATGTTGGAGACTTGGGCAATGTGAC
							CATTGC

SORBS1	NM_015385	2229	GCAGATGAGTGGA	2230	AGCGAGTGAAGAGGG	2231	ATTTCCATTGGCAT	2232	GCAGATGAGTGGAGGCTTTCTTCCAGTGCTGATGCC
							CAGCAC

SOX4	NM_003107	2233	AGATGATCTCGGG	2234	GCGCCCTTCAGTAGG	2235	CGAGTCCAGCATCT	2236	AGATGATCTCGGGAGACTGGCTCGAGTCCAGCATCT
							CCAACC

SPARC	NM_003118	2237	TCTTCCCTGTACACT	2238	AGCTCGGTGTGGGAGA	2239	TGGACCAGCACCCC	2240	TCTTCCCTGTACACTGGCAGTTCGGCCAGCTGGACCAGC
			GGCAGTTC		GGTA		ATTGACGG		ACCCCATTGACGGGTACCTCTCCCACACCGAGCT

SPARCL	NM_004684	2241	GGCACAGTGCAAG	2242	GATTGAGCTCTCTCG	2243	ACTTCATCCCAAGC	2244	GGCACAGTGCAAGTGATGACTACTTCATCCCAAGCC
							CAGGCC

SPDEF	NM_012391	2245	CCATCCGCCAGTATT	2246	GGGTGCACGAACTGGT	2247	ATCATCCGGAAGCC	2248	CCATCCGCCAGTATTACAAGAAGGGCATCATCCGGAAGC
			ACAAG		AGA		AGACATCTCC		CAGACATCTCCCAGCGCCTCGTCTACCAGTTCGT

SPINK1	NM_003122	2249	CTGCCATATGACC	2250	GTTGAAAACTGCACC	2251	ACCACGTCTCTTCA	2252	CTGCCATATGACCCTTCCAGTCCCAGGCTTCTGAAGA
							GAAGCC

SPINT1	NM_003710	2253	ATTCCCAGCACAG	2254	AGATGGCTACCACCA	2255	CTGTCGCAGTGTTC	2256	ATTCCCAGCACAGGCTCTGTGGAGATGGCTGTCGCA
							CTGGTC

SPP1	NM_001040058	2257	TCACACATGGAAAGC	2258	GTTCAGGTCCTGGGCA	2259	TGAATGGTGCATAC	2260	TCACACATGGAAAGCGAGGAGTTGAATGGTGCATACAAG
			GAGG		AC		AAGGCCATCC		GCCATCCCCGTTGCCCAGGACCTGAAC

SQLE	NM_003219	2261	ATTTTCGAGGCCAAA	2262	CCTGAGCAAGGATATT	2263	TGGGCAAGAAAAAC	2264	ATTTTCGAGGCCAAAAAATCATTTACTGGGCAAGAAAAA
			AAATC		CACG		ATCTCATTCCTTTG		CATCTCATTCCTTTGTCGTGAATATCCTTGCTC

SRC	NM_005417	2265	TGAGGAGTGGTATTT	2266	CTCTCGGGTTCTCTGC	2267	AACCGCTCTGACTC	2268	TGAGGAGTGGTATTTTGGCAAGATCACCAGACGGGAGTC
			TGGCAAGA		ATTGA		CCGTCTGGTG		AGAGCGGTTACTGCTCAATGCAGAGAACCCGAG

SRD5A1	NM_001047	2269	GGGCTGGAATCTG	2270	CCATGACTGCACAAT	2771	CCTCTCTCGGAGGC	2272	GGGCTGGAATCTGTCTAGGAGCCCTCTCTCGGAGGC
							CACAGA

SRD5A2	NM_000348	2273	GTAGGTCTCCTGGCG	2274	TCCCTGGAAGGGTAGG	2275	AGACACCACTCAGA	2276	GTAGGTCTCCTGGCGTTCTGCCAGCTGGCCTGGGGATTC
			TTCTG		AGTAA		ATCCCCAGGC		TGAGTGGTGTCTGCTTAGAGTTTACTCCTACCCTT

ST5	NM_005418	2277	CCTGTCCTGCCAG	2278	CAGCTGCACAAAACT	2279	AGTCACGAGCACCC	2280	CCTGTCCTGCCAGAGCATGGATGAAGTTTCGCTGGGT
							AGCGA

STAT1	NM_007315	2281	GGGCTCAGCTTTCAG	2282	ACATGTTCAGCTGGTC	2283	TGGCAGTTTTCTTC	2284	GGGCTCAGCTTTCAGAAGTGCTGAGTTGGCAGTTTTCTT
			AAGTG		CACA		TGTCACCAAAA		CTGTCACCAAAAGAGGTCTCAATGTGGACCAGCT

STAT3	NM_003150	2285	TCACATGCCACTTT	2286	CTTGCAGGAAGCGGC	2287	TCCTGGGAGAGATT	2288	TCACATGCCACTTTGGTGTTTCATAATCTCCTGGGAG
							GACCAG

STAT5A	NM_003152	2289	GAGGCGCTCAACATG	2290	GCCAGGAACACGAGGT	2291	CGGTTGCTCTGCAC	2292	GAGGCGCTCAACATGAAATTCAAGGCCGAAGTGCAGAGC
			AAATTC		TCTC		TTCGGCCT		AACCGGGGCCTGACCAAGGAGAACCTCGTGTTC

STAT5B	NM_012448	2293	CCAGTGGTGGTGA	2294	GCAAAAGCATTGTCC	2295	CAGCCAGGACAACA	2296	CCAGTGGTGGTGATCGTTCATGGCAGCCAGGACAAC
							ATGCG

STMN1	NM_005563	2297	AATACCCAACGCA	2298	GGAGACAATGCAAAC	2299	CACGTTCTCTGCCC	2300	AATACCCAACGCACAAATGACCGCACGTTCTCTGCC
							CGTTTC

STS	NM_000351	2301	GAAGATCCCTTTCCT	2302	GGATGATGTTCGGCCT	2303	CTGCGTGGCTCTCG	2304	GAAGATCCCTTTCCTCCTACTGTTCTTTCTGTGGGAAGC
			CCTACTGTTC		TGAT		GCTTCCCA		CGAGAGCCACGCAGCATCAAGGCCGAACATCATC

SULF1	NM_015170	2305	TGCAGTTGTAGGGAG	2306	TCTCAAGAATTGCCGT	2307	TACCGTGCCAGCAG	2308	TGCAGTTGTAGGGAGTCTGGTTACCGTGCCAGCAGAAGC
			TCTGG		TGAC		AAGCCAAAG		CAAAGAAAGAGTCAACGGCAATTCTTGAGA

SUMO1	NM_003352	2309	GTGAAGCCACCGT	2310	CCTTCCTTCTTATCCC	2311	CTGACCAGGAGGCA	2312	GTGAAGCCACCGTCATCATGTCTGACCAGGAGGCAA
							AAACCT

SVIL	NM_003174	2313	ACTTGCCCAGCAC	2314	GACACCATCCGTGTC	2315	ACCCCAGGACTGAT	2316	ACTTGCCCAGCACAAGGAAGACCCCAGGACTGATGT
							GTCAAG

TAF2	NM_003184	2317	GCGCTCCACTCTCAG	2318	CTTGTGCTCATGGTGA	2319	AGCCTCCAAACACA	2320	GCGCTCCACTCTCAGTCTTTACTAAGGAATCTACAGCCT
			TCTTT		TGGT		GTGACCACCA		CCAAACACAGTGACCACCATCACCACCATCACCAT

TARP	NM_001003799	2321	GAGCAACACGATTCT	2322	GGCACCGTTAACCAGC	2323	TCTTCATGGTGTTC	2324	GAGCAACACGATTCTGGGATCCCAGGAGGGGAACACCAT
			GGGA		TAAAT		CCCTCCTGG		GAAGACTAACGACACATACATGAAATTTAGCTG

TBP	NM_003194	2325	GCCCGAAACGCCG	2326	CGTGGCTCTCTTATCC	2327	TACCGCAGCAAACC	2328	GCCCGAAACGCCGAATATAATCCCAAGCGGTTTGCT
							GCTTGG

TFDP1	NM_007111	2329	TGCGAAGTGCTTTTG	2330	GCCTTCCAGACAGTCT	2331	CGCACCAGCATGGC	2332	TGCGAAGTGCTTTTGTTTGTTTGTTTTCGTTTGGTTAAA
			TTTGT		CCAT		AATAAGCTTT		GCTTATTGCCATGCTGGTGCGGCTATGGAGACTGTC

TFF1	NM_003225	2333	GCCCTCCCAGTGTGC	2334	CGTCGATGGTATTAGG	2335	TGCTGTTTCGACGA	2336	GCCCTCCCAGTGTGCAAATAAGGGCTGCTGTTTCGACGA
			AAAT		ATAGAAGCA		CACCGTTCG		CACCGTTCGTGGGGTCCCCTGGTGCTTCTATCCTA

TFF3	NM_003226	2337	AGGCACTGTTCATCT	2338	CATCAGGCTCCAGATA	2339	CAGAAGCGCTTGCC	2340	AGGCACTGTTCATCTCAGCTTTTCTGTCCCTTTGCTCCC
			CAGTTTTTCT		TGAACTTTC		GGGAGCAAAGG		GGCAAGCGCTTCTGCTGAAAGTTCATATCTGGAG

TGFA	NM_003236	2341	GGTGTGCCACAGACC	2342	ACGGAGTTCTTGACAG	2343	TTGGCCTGTAATCA	2344	GGTGTGCCACAGACCTTCCTACTTGGCCTGTAATCACCT
			TTCCT		AGTTTTGA		CCTGTGCAGCCTT		GTGCAGCCTTTTGTGGGCCTTCAAAACTCTGTCAA

TGFB1II	NM_001042454	2345	GCTACTTTGAGCGCT	2346	GGTCACCATCTTGTGT	2347	CAAGATGTGGCTTC	2348	GCTACTTTGAGCGCTTCTCGCCAAGATGTGGCTTCTGCA
			TCTCG		CGG		TGCAACCAGC		ACCAGCCCATCCGACACAAGATGGTGACC

TGFB2	NM_003238	2349	ACCAGTCCCCCAG	2350	CCTGGTGCTGTTGTA	2351	TCCTGAGCCCGAGG	2352	ACCAGTCCCCCAGAAGACTATCCTGAGCCCGAGGAA
							AAGTCC

TGFB3	NM_003239	2353	GGATCGAGCTCTT	2354	GCCACCGATATAGCG	2355	CGGCCAGATGAGCA	2356	GGATCGAGCTCTTCCAGATCCTTCGGCCAGATGAGC
							CATTGC

TGFBR2	NM_003242	2357	AACACCAATGGGT	2358	CCTCTTCATCAGGCC	2359	TTCTGGGCTCCTGA	2360	AACACCAATGGGTTCCATCTTTCTGGGCTCCTGATTG
							TTGCTC

THBS2	NM_003247	2361	CAAGACTGGCTACAT	2362	CAGCGTAGGTTTGGTC	2363	TGAGTCTGCCATGA	2364	CAAGACTGGCTACATCAGAGTCTTAGTGCATGAAGGAAA
			CAGAGTCTTAG		ATAGATAGG		CCTGTTTTCCTTCA		ACAGGTCATGGCAGACTCAGGACCTATCTATGA
							T

THY1	NM_006288	2365	GGACAAGACCCTC	2366	TTGGAGGCTGTGGGT	2367	CAAGCTCCCAAGAG	2368	GGACAAGACCCTCTCAGGCTGTCCCAAGCTCCCAAG
							CTTCCA

TIAM1	NM_003253	2369	GTCCCTGGCTGAA	2370	GGGCTCCCGAAGTCT	2371	TGGAGCCCTTCTCC	2372	GTCCCTGGCTGAAAATGGCCTGGAGCCCTTCTCCCAA
							CAAGAT

TIMP2	NM_003255	2373	TCACCCTCTGTGA	2374	TGTGGTTCAGGCTCTT	2375	CCCTGGGACACCCT	2376	TCACCCTCTGTGACTTCATCGTGCCCTGGGACACCCT
							GAGCAC

TIMP3	NM_000362	2377	CTACCTGCCTTGCT	2378	ACCGAAATTGGAGAG	2379	CCAAGAACGAGTGT	2380	CTACCTGCCTTGCTTTGTGACTTCCAAGAACGAGTGT
							CTCTGG

TK1	NM_003258	2381	GCCGGGAAGACCGTA	2382	CAGCGGCACCAGGTTC	2383	CAAATGGCTTCCTC	2384	GCCGGGAAGACCGTAATTGTGGCTGCACTGGATGGGACC
			ATTGT		AG		TGGAAGGTCCCA		TTCCAGAGGAAGCCATTTGGGGCCATCCTGAAC

TMPRSS	NM_005656	2385	GGACAGTGTGCAC	2386	CTCCCACGAGGAAGG	2387	AAGCACTGTGCATC	2388	GGACAGTGTGCACCTCAAAGACTAAGAAAGCACTGT
							ACCTTG

TMPRSS	DQ204772	2389	GAGGCGGAGGGCGAG	2390	ACTGGTCCTCACTCAC	2391	TAAGGCTTCCTGCC	2392	GAGGCGGAGGCGGAGGGCGAGGGGCGGGGAGCGCCGCCT
2ERGA					AACT		GCGCTCCA		GGAGCGCGGCAGGAAGCCTTATCAGTTGTGAG

TMPRSS	DQ204773	2393	GAGGCGGAGGGCGAG	2394	TTCCTCGGGTCTCCAA	2395	CCTGGAATAACCTG	2396	GAGGCGGAGGGCGAGGGGCGGGGAGCGCCGCCTGGAGCG
2ERGB					AGAT		CCGCGC		CGGCAGGTTATTCCAGGATCTTTGGAGACCCG

TNF	NM_000594	2397	GGAGAAGGGTGAC	2398	TGCCCAGACTCGGCA	2399	CGCTGAGATCAATC	2400	GGAGAAGGGTGACCGACTCAGCGCTGAGATCAATCG
							GGCCCG

TNFRSF1	NM_003844	2401	TGCACAGAGGGTGTG	2402	TCTTCATCTGATTTAC	2403	CAATGCTTCCAACA	2404	TGCACAGAGGGTGTGGGTTACACCAATGCTTCCAACAAT
0A			GGTTAC		AAGCTGTACATG		ATTTGTTTGCTTGC		TTGTTTGCTTGCCTCCCATGTACAGCTTGTAAAT
							C

TNFRSF1	NM_003842	2405	CTCTGAGACAGTGCT	2406	CCATGAGGCCCAACTT	2407	CAGACTTGGTGCCC	2408	CTCTGAGACAGTGCTTCGATGACTTTGCAGACTTGGTTG
0B			TCGATGACT		CCT		TTTGACTCC		CCCTTTGACTCCTGGGAGCCGCTCATGAGGAAGTT

TNFRSF1	NM_148901	2409	CAGAAGCTGCCAGTT	2410	CACCCACAGGTCTCCC	2411	CCTTCTCCTCTGCC	2412	CAGAAGCTGCCAGTTCCCCGAGGAAGAGCGGGGCGAGCG
8			CCC		AG		GATCGCTC		ATCGGCAGAGGAGAAGGGGCGGCTGGGAGACCT

TNFSF10	NM_003810	2413	CTTCACAGTGCTC	2414	CATCTGCTTCAGCTCG	2415	AAGTACACGTAAGT	2416	CTTCACAGTGCTCCTGCAGTCTCTCTGTGTGGCTGTA
							TACAGC

TNFSF11	NM_003701	2417	AACTGCATGTGGG	2418	TGACACCCTCTCCACT	2419	ACATGACCAGGGAC	2420	AACTGCATGTGGGCTATGGGAGGGGTTGGTCCCTGG
							CAACCC

TOP2A	NM_001067	2421	AATCCAAGGGGGA	2422	GTACAGATTTTGCCC	2423	CATATGGACTTTG	2424	AATCCAAGGGGGAGAGTGATGACTTCCATATGGACT
							ACTCAGC

TP53	NM_000546	2425	CTTTGAACCCTTGC	2426	CCCGGGACAAAGCAA	2427	AAGTCCTGGGTGC	2428	CTTTGAACCCTTGCTTGCAATAGGTGTGCGTCAGAAG
							TTCTGAC

TP63	NM_003722	2429	CCCCAAGCAGTGC	2430	GAATCGCACAGCATC	2431	CCCGGGTCTCACT	2432	CCCCAAGCAGTGCCTCTACAGTCAGTGTGGGCTCCA
							GGAGCCC

TPD52	NM_005079	2433	GCCTGTGAGATTC	2434	ATGTGCTTGGACCTC	2435	TCTGCTACCCACT	2436	GCCTGTGAGATTCCTACCTTTGTTCTGCTACCCACTG
							GCCAGAT

TPM1	NM_001018005	2437	TCTCTGAGCTCTGCA	2438	GGCTCTAAGGCAGGAT	2439	TTCTCCAGCTGAC	2440	TCTCTGAGCTCTGCATTTGTCTATTCTCCAGCTGACCCT
			TTTGTC		GCTA		CCTGGTTCTCTC		GGTTCTCTCTCTTAGCATCCTGCTTAGAGCC

TPM2	NM_213674	2441	AGGAGATGCAGCT	2442	CCACCTCTTCATATTT	2443	CCAAGCACATCGC	2444	AGGAGATGCAGCTGAAGGAGGCCAAGCACATCGCTG
							TGAGGAT

TPP2	NM_003291	2445	TAACCGTGGCATC	2446	ATGCCAACGCCATGA	2447	ATCCTGTTCAGGT	2448	TAACCGTGGCATCTACCTCCGAGATCCTGTTCAGGTG
							GGCTGCA

TPX2	NM_012112	2449	TCAGCTGTGAGCTGC	2450	ACGGTCCTAGGTTTGA	2451	CAGGTCCCATTGC	2452	TCAGCTGTGAGCTGCGGATACCGCCCGGCAATGGGACCT
			GGATA		GGTTAAGA		CGGGCG		GCTCTTAACCTCAAACCTAGGACCGT

TRA2A	NM_013293	2453	GCAAATCCAGATC	2454	CTTCACGAAGATCCC	2455	AACTGAGGCCAAA	2456	GCAAATCCAGATCCCAACACTTGCCTTGGAGTGTTTG
							CACTCCA

TRAF31P	NM_147200	2457	CCTCACAGGAACC	2458	CTGGGGCTGGGAATC	2459	TGGATCTGCCAAC	2460	CCTCACAGGAACCGAGCAGGCCTGGATCTGCCAACC
							CATAGAC

TRAM1	NM_014294	2461	CAAGAAAAGCACC	2462	ATGTCCGCGTGATTCT	2463	AGTGCTGAGCCAC	2464	CAAGAAAAGCACCAAGAGCCCCCCAGTGCTGAGCCA
							GAATTCG

TRAP1	NM_016292	2465	TTACCAGTGGCTTT	2466	TGTCCCGGTTCTAACT	2467	TTCGGCGATTTCA	2468	TTACCAGTGGCTTTCAGATGGTTCTGGAGTGTTTGAA
							AACACTC

TRIM14	NM_033220	2469	CATTCGCCTTAAG	2470	CAAGGTACCTGGCTT	2471	AACTGCCAGCTCT	2472	CATTCGCCTTAAGGAAAGCATAAACTGCCAGCTCTCA
							CAGACCC

TRO	NM_177556	2473	GCAACTGCCACCC	2474	TGGTGTGGATACTGG	2475	CCACCCAAGGCCAA	2476	GCAACTGCCACCCATACAGCTACCACCCAAGGCCAA
							ATTACC

TRPC6	NM_004621	2477	CGAGAGCCAGGACTA	2478	TAGCCGTAGCAAGGCA	2479	CTTCTCCCAGCTCC	2480	CGAGAGCCAGGACTATCTGCTCATGGACTCGGAGCTGGG
			TCTGC		GC		GAGTCCATG		AGAAGACGGCTGCCCGCAAGCCCCGCTGCCTTG

TRPV6	NM_018646	2481	CCGTAGTCCCTGCAA	2482	TCCTCACTGTTCACAC	2483	ACTTTGGGGAGCAC	2484	CCGTAGTCCCTGCAACCTCATCTACTTTGGGGAGCACCC
			CCTC		AGGC		CCTTTGTCCT		TTTGTCCTTTGCTGCCTGTGTGAACAGTGAGGA

TSTA3	NM_003313	2485	CAATTTGGACTTCT	2486	CACCTCAAAGGCCGA	2487	AACGTGCACATGAA	2488	CAATTTGGACTTCTGGAGGAAAAACGTGCACATGAA
							CGACAA

TUBB2A	NM_001069	2489	CGAGGACGAGGCT	2490	ACCATGCTTGAGGAC	2491	TCTCAGATCAATCG	2492	CGAGGACGAGGCTTAAAAACTTCTCAGATCAATCGT
							TGCATC

TYMP	NM_001953	2493	CTATATGCAGCCAGA	2494	CCACGAGTTTCTTACT	2495	ACAGCCTGCCACTC	2496	CTATATGCAGCCAGAGATGTGACAGCCACCGTGGACAGC
			GATGTGACA		GAGAATGG		ATCACAGCC		CTGCCACTCATCACAGCCTCCATTCTCAGTAAGA

TYMS	NM_001071	2497	GCCTCGGTGTGCC	2498	CGTGATGTGCGCAAT	2499	CATCGCCAGCTACG	2500	GCCTCGGTGTGCCTTTCAACATCGCCAGCTACGCCCT
							CCCTGC

UAP1	NM_003115	2501	CTGGAGACGGTCGTA	2502	GCCAAGCTTTGTAGAA	2503	TACCTGTAAACCTT	2504	CTGGAGACGGTCGTAGCTGCGGTCGCGCCGAGAAAGGTT
			GCTG		ATAGGG		TCTCGGCGCG		TACAGGTACATACATTACACCCCTATTTCTACAA

UBE2C	NM_007019	2505	TGTCTGGCGATAA	2506	ATGGTCCCTACCCATT	2507	TCTGCCTTCCCTGA	2508	TGTCTGGCGATAAAGGGATTTCTGCCTTCCCTGAATC
							ATCAGA

UBE2G1	NM_003342	2509	TGACACTGAACGA	2510	AAGCAGAGAGGAATC	2511	TTGTCCCACCAGTG	2512	TGACACTGAACGAGGTGGCTTTTGTCCCACCAGTGCC
							CCTCAT

UBE2T	NM_014176	2513	TGTTCTCAAATTGC	2514	AGAGGTCAACAAGT	2515	AGGTGCTTGGAGAC	2516	TGTTCTCAAATTGCCACCAAAAGGTGCTTGGAGACC
							CATCCC

UGDH	NM_003359	2617	GAAACTCCAGAGG	2518	CTCTGGGAACCCAGT	2519	TATACAGCACACAG	2520	GAAACTCCAGAGGGCCAGAGAGCTGTGCAGGCCCTG
							GGCCTG

UGT2B1	NM_001076	2521	AAGCCTGAAGTGG	2522	CCTCCATTTAAAACCC	2523	AAAGATGGGACTCC	2524	AAGCCTGAAGTGGAATGACTGAAAGATGGGACTCCT
							TCCTTT

UGT2B1	NM_001077	2525	TTGAGTTTGTCATG	2526	TCCAGGTGAGGTTGT	2527	ACCCGAAGGTGCTT	2528	TTGAGTTTGTCATGCGCCATAAAGGAGCCAAGCACC
							GGCTCC

UHRF1	NM_013282	2529	CTACAGGGGCAAA	2530	GGTGTCATTCAGGCG	2531	CGGCCATACCCTCT	2532	CTACAGGGGCAAACAGATGGAGGACGGCCATACCCT
							TCGACT

UTP23	NM_032334	2533	GATTGCACAAAAA	2534	GGAAAGCAGACATTC	2535	TCGAAATTGTCCTC	2536	GATTGCACAAAAATGCCAAGTTCGAAATTGTCCTCAT
							ATTTCA

VCAM1	NM_001078	2537	TGGCTTCAGGAGCTG	2538	TGCTGTCGTGATGAGA	2539	CAGGCACACACAGG	2540	TGGCTTCAGGAGCTGAATACCCTCCCAGGCACACACAGG
			AATACC		AAATAGTG		TGGGACACAAAT		TGGGACACAAATAAGGGTTTTGGAACCACTATT

VCL	NM_003373	2541	GATACCACAACTCCC	2542	TCCCTGTTAGGCGCAT	2543	AGTGGCAGCCACGG	2544	GATACCACAACTCCCATCAAGCTGTTGGCAGTGGCAGCC
			ATCAAGCT		CAG		CGCC		ACGGCGCCTCCTGATGCGCCTAACAGGGA

VCPIP1	NM_025054	2545	TTTCTCCCAGTACC	2546	TGAATAGGGAGCCTT	2547	TGGTCCATCCTCTG	2548	TTTCTCCCAGTACCATTCGTGATGGTCCATCCTCTGC
							CACCTG

VDR	NM_000376	2549	CCTCTCCTTCCAGC	2550	TCATTGCCAAACACTT	2551	CAGCATGAAGCTAA	2552	CCTCTCCTTCCAGCCTGAGTGCAGCATGAAGCTAACG
							CGCCCC

VEGFA	NM_003376	2553	CTGCTGTCTTGGG	2554	GCAGCCTGGGACCAC	2555	TTGCCTTGCTGCTC	2556	CTGCTGTCTTGGGTGCATTGGAGCCTTGCCTTGCTGC
							TACCTC

VEGFB	NM_003377	2557	TGACGATGGCCTG	2558	GGTACCGGATCATGA	2559	CTGGGCAGCACCAA	2560	TGACGATGGCCTGGAGTGTGTGCCCACTGGGCAGCA
							GTCCGG

VEGFC	NM_005429	2561	CCTCAGCAAGACGTT	2562	AAGTGTGATTGGCAAA	2563	CCTCTCTCTCAAGG	2564	CCTCAGCAAGACGTTATTTGAAATTACAGTGCCTCTCTC
			ATTTGAAATT		ACTGATTG		CCCCAAACCAGT		TCAAGGCCCCAAACCAGTAACAATCAGTTTTGCCA

VIM	NM_003380	2565	TGCCCTTAAAGGA	2566	GCTTCAACGGCAAAG	2567	ATTTCACGCATCTG	2568	TGCCCTTAAAGGAACCAATGAGTCCCTGGAACGCCA
							GCGTTC

VTI1B	NM_006370	2569	ACGTTATGCACCCCT	2570	CCGATGGAGTTTAGCA	2571	CGAAACCCCATGAT	2572	ACGTTATGCACCCCTGTCTTTCCGAAACCCCATGATGTC
			GTCTT		AGGT		GTCTAAGCTTCG		TAAGCTTCGAAACTACCGGAAGGACCTTGCTAAA

WDR19	NM_025132	2573	GAGTGGCCCAGAT	2574	GATGCTTGAGGGCTT	2575	CCCCTCGACGTATG	2576	GAGTGGCCCAGATGTCCATAAGAATGGGAGACATAC
							TCTCCC

WFDC1	NM_021197	2577	ACCCCTGCTCTGT	2578	ATACCTTCGGCCACG	2579	CTATGAGTGCCACA	2580	ACCCCTGCTCTGTCCCTCGGGCTATGAGTGCCACATC
							TCCTGA

WISP1	NM_003882	2581	AGAGGCATCCATGAA	2582	CAAACTCCACAGTACT	2583	CGGGCTGCATCAGC	2584	AGAGGCATCCATGAACTTCACACTTGCGGGCTGCATCAG
			CTTCACA		TGGGTTGA		ACACGC		GCACACGCTCCTATCAACCCAAGTACTGTGGAGTT

WNT5A	NM_003392	2585	GTATCAGGACCACAT	2586	TGTCGGAATTGATACT	2587	TTGATGCCTGTCTT	2588	GTATCAGGACCACATGCAGTACATCGGAGAAGGCGCGAA
			GCAGTACATC		GGCATT		CGCGCCTTCT		GACAGGCATCAAAGAATGCCAGTATCAATTCCG

WWOX	NM_016373	2589	ATCGCAGCTGGTG	2590	AGCTCCCTGTTGCAT	2591	CTGCTGTTTACCTT	2592	ATCGCAGCTGGTGGGTGTACACACTGCTGTTTACCTT
							GGCGAG

XIAP	NM_001167	2593	GCAGTTGGAAGACAC	2594	TGCGTGGCACTATTTT	2595	TCCCCAAATTGCAG	2596	GCAGTTGGAAGACACAGGAAAGTATCCCCAAATTGCAGA
			AGGAAAGT		CAAGA		ATTTATCAACGGC		TTTATCAACGGCTTTTATCTTGAAAATAGTGCCA

XRCC5	NM_021141	2597	AGCCCACTTCAGC	2598	AGCAGGATTCACACT	2599	TCTGGCTGAAGGCA	2600	AGCCCACTTCAGCGTCTCCAGTCTGGCTGAAGGCAG
							GTGTCA

YY1	NM_003403	2601	ACCCGGGCAACAA	2602	GACCGAGAACTCGCC	2603	TTGATCTGCACCTG	2604	ACCCGGGCAACAAGAAGTGGGAGCAGAAGCAGGTGC
							CTTCTG

ZFHX3	NM_006885	2605	CTGTGGAGCCTCT	2606	GGAGCAGGGTTGGAT	2607	ACCTGGCCCAACTC	2608	CTGTGGAGCCTCTGCCTGCGGACCTGGCCCAACTCTA
							TACCAG

ZFP36	NM_003407	2609	CATTAACCCACTC	2610	CCCCCACCATCATGA	2611	CAGGTCCCCAAGTG	2612	CATTAACCCACTCCCCTGACCTCACGCTGGGGCAGGT
							TGCAAG

ZMYND8	NM_183047	2613	GGTCTGGGCCAAA	2614	TGCCCGTCTTTATCCC	2615	CTTTTGCAGGCCAG	2616	GGTCTGGGCCAAACTGAAGGGGTTTCCATTCTGGCCT
							AATGGA

ZNF3	NM_017715	2617	CGAAGGGACTCTG	2618	GCAGGAGGTCCTCAG	2619	AGGAGGTTCCACAC	2620	CGAAGGGACTCTGCTCCAGTGAACTGGCGAGTGTGG
							TCGCCA

ZNF827	NM_178835	2621	TGCCTGAGGACCC	2622	GAGGTGGCGGAGTGA	2623	CCCGCCTTCAGAGA	2624	TGCCTGAGGACCCTCTACCGCCCCCGCCTTCAGAGA
							AGAAAC

ZWINT	NM_007057	2625	TAGAGGCCATCAA	2626	TCCGTTTCCTCTGGGC	2627	ACCAAGGCCCTGAC	2628	TAGAGGCCATCAAAATTGGCCTCACCAAGGCCCTGA
							TCAGAT

TABLE B

		SEQ
		ID
microRNA	Sequence	NO

hsa-miR-1	UGGAAUGUAAAGAAGUAUGUAU	2629

hsa-miR-103	GCAGCAUUGUACAGGGCUAUGA	2630

hsa-miR-106b	UAAAGUGCUGACAGUGCAGAU	2631

hsa-miR-10a	UACCCUGUAGAUCCGAAUUUGUG	2632

hsa-miR-133a	UUUGGUCCCCUUCAACCAGCUG	2633

hsa-miR-141	UAACACUGUCUGGUAAAGAUGG	2634

hsa-miR-145	GUCCAGUUUUCCCAGGAAUCCCU	2635

hsa-miR-146b-5p	UGAGAACUGAAUUCCAUAGGCU	2636

hsa-miR-150	UCUCCCAACCCUUGUACCAGUG	2637

hsa-miR-152	UCAGUGCAUGACAGAACUUGG	2638

hsa-miR-155	UUAAUGCUAAUCGUGAUAGGGGU	2639

hsa-miR-182	UUUGGCAAUGGUAGAACUCACACU	2640

hsa-miR-191	CAACGGAAUCCCAAAAGCAGCUG	2641

hsa-miR-19b	UG UAAACAUCCUCGACUGGAAG	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 for determining a likelihood of cancer recurrence in a patient with prostate cancer, comprising:

measuring an expression level of at least one gene in a biological sample comprising prostate tissue obtained from the patient, wherein the at least one gene comprises a gene from Tables 3A, 3B, 4A, 4B, 5A, 5B, 6A, 6B, 7A, 7B, 8A, 8B, 10A, or 10B, or genes that co-express with the at least one gene;

predicting a likelihood of cancer recurrence for the patient;

wherein an expression level of any gene in Tables 3A, 4A, 5A, 6A, 7A, 8A, and 10A is positively associated with an increased risk of recurrence, and

wherein an expression level of any gene in Tables 3B, 4B, 5B, 6B, 7B 8B, and 10B is negatively associated with a increased risk of recurrence.

2. The method of claim 1, wherein said expression level is measured using an RNA transcript of the at least one gene.

3. The method of claim 1, wherein said expression is measured using an oligonucleotide associated with the at least one gene.

4. The method of claim 1, further comprising normalizing said expression level to obtain a normalized expression level.

5. The method of claim 1, further comprising generating a report based on the Recurrence Score (RS).

6. The method of claim 5, wherein the report comprises an estimate of recurrence risk based on clinical recurrence-free interval (cRFI).

7. The method of claim 5, wherein the RS is based on a biochemical recurrence-free interval (bRFI).

8. The method of claim 1, wherein the biological sample has a positive TMPRSS2 fusion status.

9. The method of claim 1, wherein the biological sample has a negative TMPRSS2 fusion status.

10. The method of claim 1, wherein the patient has early-stage prostate cancer.

11. The method of claim 1, wherein the biological sample comprises prostate tumor tissue with the primary Gleason pattern for said prostate tumor.

12. The method of claim 1, wherein the biological samples comprises prostate tumor tissue with the highest Gleason pattern for said prostate tumor.

13. The method of claim 1, wherein the biological sample is prostate tumor tissue.

14. The method of claim 1, wherein the biological sample is non-tumor prostate tissue.

15. The method of claim 1, further comprising classifying the patient as TMPRSS2 fusion positive or negative,

wherein an expression level of any gene in Table 9A is associated with a positive TMPRSS2 fusion status, and

wherein an expression level of any gene in Table 9B is associated with a negative TMPRSS2 fusion status.

16. The method of claim 1, wherein the biological sample comprises non-tumor prostate tissue, and wherein the at least one gene comprises a gene from Tables 10A or 10B.

17. A method for determining a likelihood of upgrading or upstaging in a patient with prostate cancer, comprising:

measuring an expression level of at least one gene in a biological sample comprising prostate tissue obtained from the patient, wherein the at least one gene comprises a gene from Table 13A or 13B, or genes that co-express with the at least one gene;

wherein an expression level of any gene in Tables 13A is positively associated with an increased risk of upgrading/upstaging, and

wherein an expression level of any gene in Table 13B is negatively associated with a increased risk of upgrading/upstaging.

18. A method for determining a likelihood of cancer recurrence in a patient with prostate cancer, comprising:

measuring an expression level of at least one microRNA in a biological sample comprising prostate tissue obtained from the patient, wherein the at least one microRNA is a microRNA selected from 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; hsa-miR-200c; 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; and

normalizing said expression level to obtain a normalized expression level;

wherein a normalized expression level 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 is positively associated with an increased risk of recurrence; and

wherein a normalized expression level of 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 is negatively associated with an increased risk of recurrence.

19. The method of claim 18, further comprising measuring an expression level of at least one gene in said biological sample.

20. The method of claim 19, wherein the at least one gene is a gene selected from Tables 3A, 3B, 4A, 4B, 5A, 5B, 6A, 6B, 7A, 7B, 8A, 8B, 10A, or 10B, or genes that co-express with the at least one gene;