Gene expression panel for prognosis of prostate cancer recurrence

Abstract

Disclosed is a gene expression panel that can be used to predict prostate cancer (PCa) progression. Some embodiments provide methods for predicting clinical recurrence of PCa. Some embodiments provide a method for predicting progression of prostate cancer in an individual, the method comprising: (a) receiving expression levels of a collection of signature genes from a biological sample taken from said individual, wherein said collection of signature genes comprises at least two genes selected from the group consisting of: NKX2-1, UPK1A, ADRA2C, ABCC11, MMP11, CPVL, ZYG11A, CLEC4F, OAS2, PGC, UPK3B, PCBP3, ABLIM1, EDARADD, GPR81, MYBPC1, F10, KCNA3, GLDC, KCNQ2, RAPGEF1, TUBB2B, MB, DUOXA1, C2orf43, DUOX1, PCA3 and NPR3; (b) applying the expression levels to a predictive model relating expression levels of said collection of signature genes with prostate cancer progression; and (c) evaluating an output of said predictive model to predict progression of prostate cancer in said individual. Systems are also provided for predicting progression and/or recurrence of PCa.

What is claimed is: 
     
         1 . A system for predicting progression of prostate cancer in an individual, the system comprising hardware logic designed or configured to preform operations comprising:
 (a) receiving information regarding expression levels of a collection of signature genes from a biological sample taken from said individual,
 (i) wherein said collection of signature genes comprises at least two genes selected from the group consisting of: NKX2-1, UPK1A, ADRA2C, ABCC11, MMP11, CPVL, ZYG11A, CLEC4F, OAS2, PGC, UPK3B, PCBP3, ABLIM1, EDARADD, GPR81, MYBPC1, F10, KCNA3, GLDC, KCNQ2, RAPGEF1, TUBB2B, MB, DUOXA1, C2orf43, DUOX1, PCA3 and NPR3, or 
 (ii) wherein said collection of signature genes comprises at least one gene selected from the group consisting of: NKX2-1, UPK1A, ABCC11, MMP11, CPVL, ZYG11A, CLEC4F, OAS2, PGC, UPK3B, PCBP3, EDARADD, GPR81, MYBPC1, KCNA3, GLDC, KCNQ2, RAPGEF1, TUBB2B, MB, DUOXA1, C2orf43, DUOX1, and NPR3, or 
 (iii) wherein said collection of signature genes comprises at least two genes selected from the group consisting of: NKX2-1, UPK1A, ADRA2C, ABCC11, MMP11, CPVL, ZYG11A, CLEC4F, OAS2, and PGC, or 
 (iv) wherein said collection of signature genes comprises at least two genes selected from the group consisting of: ZYG11A, MMP11, MYBPC1, DUOX1, EDARADD, PGC, GPR81, NKX2-1, ABLIM1, and ABCC11; 
   (b) applying the expression levels to a predictive model relating expression levels of said collection of signature genes with prostate cancer progression; and   (c) evaluating an output of said predictive model to predict progression of prostate cancer in said individual.   
     
     
         2 . The system of  claim 1 , wherein the collection of signature genes comprises NKX2-1. 
     
     
         3 . The system of  claim 1 , further comprising apparatus configured to determine expression levels of nucleic acids from a biological sample taken from the individual. 
     
     
         4 . The system of  claim 3 , wherein the apparatus comprises a microarray. 
     
     
         5 . The system of  claim 3 , wherein the apparatus comprises a next generation sequencer. 
     
     
         6 . The system of  claim 3 , wherein the apparatus comprises a qPCR apparatus. 
     
     
         7 . The system of  claim 1 , wherein said logic is further designed or configured such that the output of the predictive model predicts a likelihood of clinical or biochemical recurrence of prostate cancer in the individual after said individual has undergone treatment for prostate cancer. 
     
     
         8 . The system of  claim 1 , wherein said logic is further designed or configured to apply at least one of Gleason score, year of surgical operation for prostate cancer, pre-operative PSA level, and age to the predictive model, wherein the predictive model relates the at least one of Gleason score, year of surgical operation for prostate cancer, pre-operative PSA level, and age to prostate cancer progression. 
     
     
         9 . The system of  claim 1 , wherein said logic is further designed or configured to evaluate the output of the predictive model to determine whether or not the individual falls in a high risk group. 
     
     
         10 . The system of  claim 1 , wherein said logic is further designed or configured to develop said predictive model by selecting the collection of signature genes from more than about 1000 genes. 
     
     
         11 . The system of  claim 1 , wherein said logic is further designed or configured to develop said predictive model using stability selection. 
     
     
         12 . The system of  claim 1 , wherein said logic is further designed or configured to develop said predictive model using logistic regression. 
     
     
         13 . The system of  claim 1 , wherein said logic is further designed or configured to develop said predictive model by selecting genes using stability selection with elastic-net regularized logistic regression. 
     
     
         14 . The system of  claim 1 , wherein said logic to apply said expression levels of the collection of signature genes to the predictive model comprises logic to weight said expression levels according to stability rankings of the collection of signature genes. 
     
     
         15 . The system of  claim 1 , wherein said logic to apply said expression levels of the collection of signature genes to said predictive model comprises logic to weight said expression levels according to predictive power rankings of the collection of signature genes. 
     
     
         16 . The system of  claim 1 , wherein said logic is further designed or configured such that said predictive model has an area under the curve that is larger than that of a predictive model having only Gleason score. 
     
     
         17 . The system of  claim 1 , wherein said logic is further designed or configured such that said predictive model has an area under the curve that is larger than that of a predictive model having only Gleason score, pre-operative PSA level, and age. 
     
     
         18 . A system for predicting progression of prostate cancer in an individual, the system comprising:
 (a) input apparatus configured to receive information regarding expression levels of a collection of signature genes from a biological sample taken from said individual,
 (i) wherein said collection of signature genes comprises at least two genes selected from the group consisting of: NKX2-1, UPK1A, ADRA2C, ABCC11, MMP11, CPVL, ZYG11A, CLEC4F, OAS2, PGC, UPK3B, PCBP3, ABLIM1, EDARADD, GPR81, MYBPC1, F10, KCNA3, GLDC, KCNQ2, RAPGEF1, TUBB2B, MB, DUOXA1, C2orf43, DUOX1, PCA3 and NPR3, or 
 (ii) wherein said collection of signature genes comprises at least one gene selected from the group consisting of: NKX2-1, UPK1A, ABCC11, MMP11, CPVL, ZYG11A, CLEC4F, OAS2, PGC, UPK3B, PCBP3, EDARADD, GPR81, MYBPC1, KCNA3, GLDC, KCNQ2, RAPGEF1, TUBB2B, MB, DUOXA1, C2orf43, DUOX1, and NPR3, or 
 (iii) wherein said collection of signature genes comprises at least two genes selected from the group consisting of: NKX2-1, UPK1A, ADRA2C, ABCC11, MMP11, CPVL, ZYG11A, CLEC4F, OAS2, and PGC, or 
 (iv) wherein said collection of signature genes comprises at least two genes selected from the group consisting of: ZYG11A, MMP11, MYBPC1, DUOX1, EDARADD, PGC, GPR81, NKX2-1, ABLIM1, and ABCC11; 
   (b) processing apparatus configured to apply the information regarding the expression levels to a predictive model relating expression levels of said collection of signature genes with prostate cancer progression; and   (c) output apparatus configured to provide output regarding progression of prostate cancer in said individual based on the application of the predictive model.   
     
     
         19 . The system of  claim 18 , wherein the collection of signature genes comprises NKX2-1. 
     
     
         20 . The system of  claim 18 , wherein the input apparatus comprises apparatus configured to determine expression levels of nucleic acids from a biological sample taken from the individual.