Use of genomic signatures to predict responsiveness of patients with prostate cancer to post-operative radiation therapy

Abstract

Methods, compositions, and kits for identifying individuals who will be responsive to post-operative radiation therapy for treatment of prostate cancer are disclosed. In particular, the invention relates to a genomic signature based on expression levels of DNA Damage Repair genes that can be used to identify individuals likely to benefit from post-operative radiation therapy after a prostatectomy.

1 - 30 . (canceled) 
     
     
         31 . A method for treating a subject having prostate cancer, comprising:
 a) obtaining a post-operative radiation therapy outcome score (PORTOS) that has been calculated using a level of expression of a plurality of genes in the biological sample, wherein said plurality of genes comprises one or more genes selected from the group consisting of DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A, MUM1, TOP2A, GNG11, CDKN3, HCLS1, DTL, IL7R, UBA7, NEK1, CDKN2AIP, APEX2, KIF23, SULF2, PLK2, EME1, and BIN2;   b) determining whether or not the subject is likely to benefit from post-operative radiation therapy based on the PORTOS score, wherein a PORTOS greater than 0 indicates that the subject will benefit from the post-operative radiation therapy and a PORTOS less than or equal to 0 indicates that the subject will not benefit from the post-operative radiation therapy; and   c) if the PORTOS indicates that the subject will benefit from the radiation therapy, then administering the post-operative radiation therapy to the subject, and if the PORTOS does not indicate that the subject will benefit from the post-operative radiation therapy, then administering a cancer treatment other than the post-operative radiation therapy to the subject.   
     
     
         32 . The method of  claim 31 , wherein the subject has previously undergone a radical prostatectomy. 
     
     
         33 . The method of  claim 31 , wherein the prostate cancer has not metastasized. 
     
     
         34 . The method of  claim 31 , wherein the biological sample is a biopsy. 
     
     
         35 . The method of  claim 31 , wherein the biological sample is a tumor sample. 
     
     
         36 . The method of  claim 31 , wherein the subject is a human being. 
     
     
         37 . The method of  claim 31 , wherein the level of expression has been measured by performing microarray analysis, polymerase chain reaction (PCR), reverse transcriptase polymerase chain reaction (RT-PCR), a Northern blot, or serial analysis of gene expression (SAGE). 
     
     
         38 . The method of  claim 31 , wherein said administering post-operative radiation therapy to the subject, or administering a cancer treatment other than the post-operative radiation therapy to the subject further comprises performing chemotherapy, immunotherapy, hormonal therapy, biologic therapy, or any combination thereof. 
     
     
         39 . The method of  claim 31 , wherein the PORTOS indicates that the subject will benefit from the radiation therapy, and administering the post-operative radiation therapy to the subject. 
     
     
         40 . The method of  claim 31 , wherein the plurality of genes comprises at least 2 genes selected from the group consisting of DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A, MUM1, TOP2A, GNG11, CDKN3, HCLS1, DTL, IL7R, UBA7, NEK1, CDKN2AIP, APEX2, KIF23, SULF2, PLK2, EME1, and BIN2. 
     
     
         41 . The method of  claim 31 , wherein the plurality of genes comprises at least 5 genes selected from the group consisting of DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A, MUM1, TOP2A, GNG11, CDKN3, HCLS1, DTL, IL7R, UBA7, NEK1, CDKN2AIP, APEX2, KIF23, SULF2, PLK2, EME1, and BIN2. 
     
     
         42 . The method of  claim 31 , wherein the plurality of genes comprises at least 10 genes selected from the group consisting of DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A, MUM1, TOP2A, GNG11, CDKN3, HCLS1, DTL, IL7R, UBA7, NEK1, CDKN2AIP, APEX2, KIF23, SULF2, PLK2, EME1, and BIN2. 
     
     
         43 . The method of  claim 31 , wherein the plurality of genes comprises at least 15 genes selected from the group consisting of DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A, MUM1, TOP2A, GNG11, CDKN3, HCLS1, DTL, IL7R, UBA7, NEK1, CDKN2AIP, APEX2, KIF23, SULF2, PLK2, EME1, and BIN2. 
     
     
         44 . The method of  claim 31 , wherein the plurality of genes comprises at least 20 genes selected from the group consisting of DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A, MUM1, TOP2A, GNG11, CDKN3, HCLS1, DTL, IL7R, UBA7, NEK1, CDKN2AIP, APEX2, KIF23, SULF2, PLK2, EME1, and BIN2. 
     
     
         45 . The method of  claim 31 , wherein the plurality of genes comprises one or more genes selected from the group consisting of KRT14, PTPN22, ANLN, DTL, EME1, and BIN2. 
     
     
         46 . The method of  claim 31 , wherein the plurality of genes comprises KRT14, PTPN22, ANLN, DTL, EME1, and BIN2. 
     
     
         47 . The method of  claim 31 , wherein the plurality of genes comprises one or more genes selected from the group consisting of ARHGAP15, BIN2, DRAM1, HCLS1, IL7R, PTPN2, and SULF2. 
     
     
         48 . The method of  claim 31 , wherein the plurality of genes comprises ARHGAP15, BIN2, DRAM1, HCLS1, IL7R, PTPN2, and SULF2. 
     
     
         49 . The method of  claim 31 , wherein the plurality of genes comprises a pair of genes selected from:
 DRAM1 and BIN2;   SULF2 and BIN2;   ZMAT3 and BIN2;   HCLS1 and BIN2;   DTL and BIN2;   EME1 and BIN2;   IL7R and BIN2;   KRT14 and EME1;   KRT14 and BIN2;   PTPN22 and CDKN2AIP;   PTPN22 and PLK2;   IL7R and EME1;   PTPN22 and ANLN;   PTPN22 and APEX2;   DTL and EME1;   PTPN22 and CDKN3;   PTPN22 and UBA7;   DTL and IL7R;   PTPN22 and RPS27A;   PTPN22 and MUM1;   RPS27A and BIN2;   CDKN2AIP and PLK2;   KRT14 and DTL;   GNG11 and BIN2;   PTPN22 and ZMAT3;   GNG11 and EME1;   PTPN22 and HCLS1;   APEX2 and PLK2;   DRAM1 and PTPN22;   ZMAT3 and EME1;   UBA7 and EME1;   SULF2 and EME1;   PTPN22 and NEK1;   HCLS1 and EME1;   UBA7 and BIN2;   NEK1 and PLK2;   DRAM1 and EME1;   ANLN and PLK2;   MUM1 and BIN2;   PTPN22 and IL7R;   KRT14 and IL7R;   ZMAT3 and DTL;   MUM1 and PLK2;   KIF23 and BIN2;   CDKN3 and PLK2;   DTL and UBA7;   IL7R and SULF2;   DRAM1 and DTL;   RPS27A and EME1;   HCLS1 and DTL;   PTPN22 and GNG11;   RPS27A and PLK2;   KIF23 and EME1;   UBA7 and PLK2;   DTL and SULF2;   GNG11 and DTL;   ZMAT3 and PLK2;   HCLS1 and PLK2;   KRT14 and SULF2;   DRAM1 and PLK2;   KRT14 and GNG11;   PTPN22 and SULF2;   RPS27A and DTL;   MUM1 and EME1; and   KRT14 and KIF23.   
     
     
         50 . The method of  claim 31 , wherein the post-operative radiation therapy is selected from the group consisting of intensity-modulated radiation therapy (IMRT), image-guided radiation therapy (IGRT), stereotactic radiosurgery (SRS), stereotactic body radiation therapy (SBRT), proton therapy, and brachytherapy.