Methods for prostate cancer detection and treatment

Abstract

The present invention is directed to methods for detecting a prostate cancer, methods for determining whether a prostate cancer is stable or progressive, low or high Gleason score, methods for differentiating benign prostate hyperplasia (BPH) from prostate cancer, methods for determining the completeness of surgery, and methods for evaluating the response to a prostate cancer therapy.

What is claimed is: 
     
         1 . A method for detecting a prostate cancer in a subject in need thereof, the method comprising:
 determining the expression level of at least 38 biomarkers from a test sample from the subject by contacting the test sample with a plurality of agents specific to detect the expression of the at least 38 biomarkers, wherein the at least 38 biomarkers comprise AAMP, ANO7, AR, AR-V7, C16orf89, CHTOP, COL1A1, EDC4, FGFR2, FXYD7, FYCO1, HNRNPU, HPN, KRT15, KRT23, MAN2B2, MAX, MRPS25, NDUFS2, PPARGC1A, PPRC1, RAD23A, REPIN1, SDR39U1, SETBP1, SLC14A1, SLC18A2, SMC4, SPARC, SQLE, STRIP1, STX12, TMPRSS2_1, TMPRSS2_2, TRIM29, UNC45A, XPC, and a housekeeping gene;   normalizing the expression level of each of AAMP, ANO7, AR, AR-V7, C16orf89, CHTOP, COL1A1, EDC4, FGFR2, FXYD7, FYCO1, HNRNPU, HPN, KRT15, KRT23, MAN2B2, MAX, MRPS25, NDUFS2, PPARGC1A, PPRC1, RAD23A, REPIN1, SDR39U1, SETBP1, SLC14A1, SLC18A2, SMC4, SPARC, SQLE, STRIP1, STX12, TMPRSS2_1, TMPRSS2_2, TRIM29, UNC45A, and XPC to the expression level of the housekeeping gene, thereby obtaining a normalized expression level of each of AAMP, ANO7, AR, AR-V7, C16orf89, CHTOP, COL1A1, EDC4, FGFR2, FXYD7, FYCO1, HNRNPU, HPN, KRT15, KRT23, MAN2B2, MAX, MRPS25, NDUFS2, PPARGC1A, PPRC1, RAD23A, REPIN1, SDR39U1, SETBP1, SLC14A1, SLC18A2, SMC4, SPARC, SQLE, STRIP1, STX12, TMPRSS2_1, TMPRSS2_2, TRIM29, UNC45A, and XPC;   inputting each normalized expression level into an algorithm to generate a score;   comparing the score with a first predetermined cutoff value; and   producing a report, wherein the report identifies the presence of a prostate cancer in the subject when the score is equal to or greater than the first predetermined cutoff value or identifies the absence of a prostate cancer in the subject when the score is less than the first predetermined cutoff value.   
     
     
         2 - 5 . (canceled) 
     
     
         6 . A method for evaluating the response of a subject having a prostate cancer to a first therapy, the method comprising: 
 (1) at a first time point:
 (a) determining the expression level of at least 38 biomarkers from a test sample from the subject by contacting the test sample with a plurality of agents specific to detect the expression of the at least 38 biomarkers, wherein the at least 38 biomarkers comprise AAMP, ANO7, AR, AR-V7, C16orf89, CHTOP, COL1A1, EDC4, FGFR2, FXYD7, FYCO1, HNRNPU, HPN, KRT15, KRT23, MAN2B2, MAX, MRPS25, NDUFS2, PPARGC1A, PPRC1, RAD23A, REPIN1, SDR39U1, SETBP1, SLC14A1, SLC18A2, SMC4, SPARC, SQLE, STRIP1, STX12, TMPRSS2_1, TMPRSS2_2, TRIM29, UNC45A, XPC, and a housekeeping gene; 
 (b) normalizing the expression level of each of AAMP, ANO7, AR, AR-V7, C16orf89, CHTOP, COL1A1, EDC4, FGFR2, FXYD7, FYCO1, HNRNPU, HPN, KRT15, KRT23, MAN2B2, MAX, MRPS25, NDUFS2, PPARGC1A, PPRC1, RAD23A, REPIN1, SDR39U1, SETBP1, SLC14A1, SLC18A2, SMC4, SPARC, SQLE, STRIP1, STX12, TMPRSS2_1, TMPRSS2_2, TRIM29, UNC45A, and XPC to the expression level of the housekeeping gene, thereby obtaining a normalized expression level of each of AAMP, ANO7, AR, AR-V7, C16orf89, CHTOP, COL1A1, EDC4, FGFR2, FXYD7, FYCO1, HNRNPU, HPN, KRT15, KRT23, MAN2B2, MAX, MRPS25, NDUFS2, PPARGC1A, PPRC1, RAD23A, REPIN1, SDR39U1, SETBP1, SLC14A1, SLC18A2, SMC4, SPARC, SQLE, STRIP1, STX12, TMPRSS2_1, TMPRSS2_2, TRIM29, UNC45A, and XPC; 
 (c) inputting each normalized expression level into an algorithm to generate a first score; 
   (2) at a second time point, wherein the second time point is after the first time point and after the administration of the first therapy to the subject:
 (d) determining the expression level of the at least 38 biomarkers from a test sample from the subject by contacting the test sample with a plurality of agents specific to detect the expression of the at least 38 biomarkers; 
 (e) normalizing the expression level of each of AAMP, ANO7, AR, AR-V7, C16orf89, CHTOP, COL1A1, EDC4, FGFR2, FXYD7, FYCO1, HNRNPU, HPN, KRT15, KRT23, MAN2B2, MAX, MRPS25, NDUFS2, PPARGC1A, PPRC1, RAD23A, REPIN1, SDR39U1, SETBP1, SLC14A1, SLC18A2, SMC4, SPARC, SQLE, STRIP1, STX12, TMPRSS2_1, TMPRSS2_2, TRIM29, UNC45A, and XPC to the expression level of the housekeeping gene, thereby obtaining a normalized expression level of each of AAMP, ANO7, AR, AR-V7, C16orf89, CHTOP, COL1A1, EDC4, FGFR2, FXYD7, FYCO1, HNRNPU, HPN, KRT15, KRT23, MAN2B2, MAX, MRPS25, NDUFS2, PPARGC1A, PPRC1, RAD23A, REPIN1, SDR39U1, SETBP1, SLC14A1, SLC18A2, SMC4, SPARC, SQLE, STRIP1, STX12, TMPRSS2_1, TMPRSS2_2, TRIM29, UNC45A, and XPC; 
 (f) inputting each normalized expression level into an algorithm to generate a second score; 
   (3) comparing the first score with the second score; and   (4) producing a report, wherein the report identifies that the subject is responsive to the first therapy when the second score is significantly decreased as compared to the first score or identifies that the subject is not responsive to the first therapy when the second score is not significantly decreased as compared to the first score.   
     
     
         7 - 33 . (canceled) 
     
     
         34 . A method of treating prostate cancer in a subject comprising:
 determining the expression level of at least 38 biomarkers from a test sample from the subject by contacting the test sample with a plurality of agents specific to detect the expression of the at least 38 biomarkers, wherein the at least 38 biomarkers comprise AAMP, ANO7, AR, AR-V7, C16orf89, CHTOP, COL1A1, EDC4, FGFR2, FXYD7, FYCO1, HNRNPU, HPN, KRT15, KRT23, MAN2B2, MAX, MRPS25, NDUFS2, PPARGC1A, PPRC1, RAD23A, REPIN1, SDR39U1, SETBP1, SLC14A1, SLC18A2, SMC4, SPARC, SQLE, STRIP1, STX12, TMPRSS2_1, TMPRSS2_2, TRIM29, UNC45A, XPC, and a housekeeping gene, wherein the housekeeping gene is TOX4;   normalizing the expression level of each of AAMP, ANO7, AR, AR-V7, C16orf89, CHTOP, COL1A1, EDC4, FGFR2, FXYD7, FYCO1, HNRNPU, HPN, KRT15, KRT23, MAN2B2, MAX, MRPS25, NDUFS2, PPARGC1A, PPRC1, RAD23A, REPIN1, SDR39U1, SETBP1, SLC14A1, SLC18A2, SMC4, SPARC, SQLE, STRIP1, STX12, TMPRSS2_1, TMPRSS2_2, TRIM29, UNC45A, and XPC to the expression level of the housekeeping gene, thereby obtaining a normalized expression level of each of AAMP, ANO7, AR, AR-V7, C16orf89, CHTOP, COL1A1, EDC4, FGFR2, FXYD7, FYCO1, HNRNPU, HPN, KRT15, KRT23, MAN2B2, MAX, MRPS25, NDUFS2, PPARGC1A, PPRC1, RAD23A, REPIN1, SDR39U1, SETBP1, SLC14A1, SLC18A2, SMC4, SPARC, SQLE, STRIP1, STX12, TMPRSS2_1, TMPRSS2_2, TRIM29, UNC45A, and XPC;   inputting each normalized expression level into an algorithm to generate a score, wherein the algorithm is a product of a model of prostate cancer derived using the XGB algorithm;   comparing the score with a first predetermined cutoff value;   determining that the score is equal to or greater than the predetermined cutoff value, thereby identifying the subject as having prostate cancer; and   administering to the subject identified as having prostate cancer a therapy, wherein the therapy comprises radiation therapy, cryotherapy, hormone therapy, chemotherapy, vaccine treatment, bone-directed treatment, or a combination thereof.   
     
     
         35 . The method of  claim 34 , wherein the first predetermined cutoff value is at least 33% on a scale of 0-100%. 
     
     
         36 . The method of  claim 34 , wherein the predetermined cutoff value has a sensitivity of identifying the subject as having prostate cancer that is-at least 92%. 
     
     
         37 . The method of  claim 34 , wherein the predetermined cutoff value has a specificity of identifying the subject as having prostate cancer that is at least 95%. 
     
     
         38 . The method of  claim 34 , wherein at least one of the at least 38 biomarkers is RNA, cDNA, or protein. 
     
     
         39 . The method of  claim 38 , wherein when the biomarker is RNA, the RNA is reverse transcribed to produce cDNA, and the produced cDNA expression level is detected. 
     
     
         40 . The method of  claim 34 , wherein the first predetermined cutoff value is derived from a plurality of reference samples obtained from subjects not having or not diagnosed with a prostate cancer. 
     
     
         41 . The method of  claim 34 , wherein the test sample comprises blood, serum, plasma, or neoplastic tissue. 
     
     
         42 . The method of  claim 40 , wherein reference sample comprises blood, serum, plasma, or non-neoplastic tissue. 
     
     
         43 . The method of  claim 34 , wherein the therapy comprises hormone therapy, wherein the hormone therapy comprises androgen suppression therapy. 
     
     
         44 . The method of  claim 34 , wherein the therapy comprises chemotherapy, wherein the chemotherapy comprises docetaxel, cabazitaxel, mitoxantrone, estramustine, or a combination thereof. 
     
     
         45 . The method of  claim 34 , wherein the therapy comprises vaccine treatment, wherein the vaccine treatment comprises Sipuleucel-T. 
     
     
         46 . The method of  claim 34 , wherein the therapy comprises bone-directed treatment, wherein the bone-directed treatment comprises a bisphosphonate, denosumab, a corticosteroid, or a combination thereof.