Gene signatures for cancer prognosis

Abstract

Biomarkers and methods using the biomarkers for the prediction of the recurrence risk of cancer in a patient are provided.

1 .- 26 . (canceled) 
     
     
         27 . A method for prognosing a prostate cancer patient who has undergone radical prostatectomy comprising:
 detecting in a prostate tumor sample from the patient expression of a panel of genes comprising the following cell cycle genes: MCM10, ASPM, DLGAP5, CENPF, CDC20, FOXM1, TOP2A, NUSAP1, CDKN3, KIFI1, KIF20A, BUB1B, RAD54L, CEP55, CDCAS, TKl, DTL, PRC1, PTTG1, CDC2, ORC6L, PLKI, C18orf24, BIRC5, RRM2, CENPM, RAD51, KIAAO101, CDCA3, PBK, and ASF1B, normalized to one or more housekeeping genes;   determining a cell cycle progression (CCP) score of the patient sample, and   determining a poor prognosis for the patient when the CCP score exceeds a threshold value, and determining a good prognosis for the patient when the CCP score is less than the threshold value,
 wherein the threshold value is determined as the lowest CCP score in a low clinical risk group who had recurrence of prostate cancer, wherein recurrence is determined by PSA, and wherein the low clinical risk group is identified by:
 determining the clinical risk of recurrence of prostate cancer after prostatectomy surgery for a control group of prostate cancer patients using a nomogram, wherein the nomogram uses at least two of organ-confined disease, Gleason score, and preoperative PSA; and 
 identifying a low clinical risk group in the control group using a clustering tool for determining the cluster with the lowest clinical risk of recurrence of prostate cancer after surgery based on the nomogram. 
 
   
     
     
         28 . The method of  claim 27 , wherein the CCP score of a sample is defined as the average expression of the panel of genes. 
     
     
         29 . The method of  claim 27 , wherein the CCP score of a sample is defined as the weighted average expression of the panel of genes, wherein the combined weight given to the cell cycle genes is at least 40%. 
     
     
         30 . The method of  claim 27 , wherein at least 75% of the panel of genes are cell cycle genes. 
     
     
         31 . The method of  claim 27 , wherein the determining comprises measuring mRNA levels of the panel of genes. 
     
     
         32 . The method of  claim 27 , wherein the housekeeping genes are selected from RPL38, UBA52, PSMCI, RPL4, RPL37, RPS29, SLC25A3, CLTC, TXNLI, PSMAI, RPL8, MMADHC, RPL13A, PPP2CA, and MRFAPI. 
     
     
         33 . The method of  claim 27 , wherein the expression is measured by qPCR or qRT-PCR. 
     
     
         34 . A method for prognosing a prostate cancer patient who has undergone radical prostatectomy comprising:
 detecting in a prostate tumor sample from the patient expression of a panel of genes comprising the following cell cycle genes: ASF1B, ASPM, BIRC5, BUB1B, C18orf24, CDCl2, CDCl20, CDCA3, CDCA8, CDKN3, CENPF, CENPM, CEP55, DLGAP5, DTL, FOXM1, KIAA0101, KIF11, KIF20A, MCM10, NUSAP1, ORC6L, PBK, PLK1, PRC1, PTTG1, RAD51, RAD54L, RRM2, TK1 and TOP2A, normalized to one or more housekeeping genes;   determining a cell cycle progression (CCP) score of the patient sample, and   determining a poor prognosis for the patient when the CCP score exceeds a threshold value, and determining a good prognosis for the patient when the CCP score is less than the threshold value,
 wherein the threshold value is determined as the lowest CCP score in a low clinical risk group who had recurrence of prostate cancer, wherein recurrence is determined by PSA, and wherein the low clinical risk group is identified by:
 determining the clinical risk of recurrence of prostate cancer after prostatectomy surgery for a control group of prostate cancer patients using a nomogram, wherein the nomogram uses at least two of organ-confined disease, Gleason score, and preoperative PSA; and 
 identifying a low clinical risk group in the control group using a clustering tool for determining the cluster with the lowest clinical risk of recurrence of prostate cancer after surgery based on the nomogram. 
 
   
     
     
         35 . The method of  claim 34 , wherein the CCP score of a sample is defined as the average expression of the panel of genes. 
     
     
         36 . The method of  claim 34 , wherein the CCP score of a sample is defined as the weighted average expression of the panel of genes, wherein the combined weight given to the cell cycle genes is at least 40%. 
     
     
         37 . The method of  claim 34 , wherein at least 75% of the panel of genes are cell cycle genes. 
     
     
         38 . The method of  claim 34 , wherein the determining comprises measuring mRNA levels of the panel of genes. 
     
     
         39 . The method of  claim 32 , wherein the housekeeping genes are selected from RPL38, UBA52, PSMCI, RPL4, RPL37, RPS29, SLC25A3, CLTC, TXNLI, PSMAI, RPL8, MMADHC, RPL13A, PPP2CA, and MRFAPI. 
     
     
         40 . The method of  claim 32 , wherein the expression is measured by qPCR or qRT-PCR. 
     
     
         41 . A system for prognosing prostate cancer, comprising:
 (1) a sample analyzer for determining the expression levels of a panel of genes in a fresh frozen tumor sample including at least 4 cell-cycle genes selected from Table 4 or Table 16, wherein the sample analyzer contains the tumor sample which is from a patient identified as having prostate cancer, or cDNA molecules from mRNA expressed from the panel of genes; and   (2) a processor programmed for:   (i) (a) receiving gene expression data on at least 4 test genes selected from the panel of genes, (b) weighting the determined expression of each of the test genes, and (c) combining the weighted expression to provide a test value, wherein said at least 4 test genes are cell-cycle genes selected from Table 4 or Table 16; and   (ii) for comparing the test value to one or more reference values each associated with a predetermined degree of risk of cancer recurrence or progression of the prostate cancer.   
     
     
         42 . The system of  claim 41 , further comprising a display module displaying the comparison between the test value to the one or more reference values, or displaying a result of the comparing step.