Gene signatures for cancer characterization and methods of use

Abstract

An assay system and method for generating quantitative data for a subject by determining an expression level of a biomarker panel in a sample obtained from the subject, the biomarker panel having at least one biomarker selected from a first biomarker group including the genes CDC45, CENPI, CLSPN, ERCC6L, EXO1, NCAPG, and optionally at least one additional biomarker selected from a second biomarker group including the genes BUB1B, CDK1, E2F7, GSG2, NUSAP1, RAD51, and RRM2 in any combination, wherein the expression level is obtained by measuring expression of the biomarker panel in the sample, and wherein the subject has a cancer, or is suspected of having a cancer. The cancer may be, for example, prostate cancer, brain cancer, lung cancer, breast cancer, bladder cancer, or ovarian cancer.

1 - 66 . (canceled) 
     
     
         67 . A method for generating quantitative data for a subject, comprising determining an expression level of a biomarker panel in a sample obtained from the subject, the biomarker panel comprising at least five biomarkers selected from the group consisting of the genes CDC45, CENPI, CLSPN, ERCC6L, EXO1, NCAPG, BUB1B, CDK1, E2F7, GSG2, NUSAP1, RAD51, and RRM2, wherein at least three of the at least five biomarkers are selected from CDC45, CENPI, CLSPN, ERCC6L, EXO1, NCAPG, wherein the expression level is obtained by measuring expression of each biomarker of the biomarker panel in the sample. 
     
     
         68 . The method of  claim 67 , wherein the biomarker panel comprises CDC45. 
     
     
         69 . The method of  claim 67 , wherein the biomarker panel comprises CDC45 and NCAPG. 
     
     
         70 . The method of  claim 67 , wherein the biomarker panel comprises CDC45, NCAPG, and CLSPN. 
     
     
         71 . The method of  claim 67 , wherein the biomarker panel comprises at least four biomarkers selected from CDC45, CENPI, CLSPN, ERCC6L, EXO1, NCAPG. 
     
     
         72 . The method of  claim 67 , wherein the biomarker panel comprises at least five biomarkers selected from CDC45, CENPI, CLSPN, ERCC6L, EXO1, NCAPG. 
     
     
         73 . The method of  claim 67 , wherein the biomarker panel comprises CDC45, CENPI, CLSPN, ERCC6L, EXO1, NCAPG. 
     
     
         74 . The method of  claim 67 , wherein the biomarker panel comprises CDC45, CENPI, CLSPN, ERCC6L, EXO1, NCAPG, BUB1B, CDK1, NUSAP1, RAD51, and RRM2. 
     
     
         75 . The method of  claim 67 , wherein the subject has or is suspected of having a cancer selected from the group consisting of prostate cancer, brain cancer, lung cancer, breast cancer, bladder cancer, and ovarian cancer. 
     
     
         76 . The method of  claim 75 , further comprising applying to the subject active surveillance, hormonal therapy, chemotherapy, immunotherapy, radiation therapy, cryotherapy, and/or surgery based on whether the subject is at risk for the cancer, has been previously treated for the cancer, or has been diagnosed with the cancer but has not been previously treated for the cancer. 
     
     
         77 . The method of  claim 76 , wherein active surveillance is applied to the subject when the expression level of the at least one biomarker is less than a threshold index value, and wherein one or more of hormonal therapy, chemotherapy, immunotherapy, radiation therapy, and surgery is applied to the subject when the expression level of the at least one biomarker is equal to or greater than the threshold index value. 
     
     
         78 . The method of  claim 76 , wherein the cancer is prostate cancer, the subject has been previously treated for prostate cancer, and the previous treatment for the prostate cancer was radical prostatectomy. 
     
     
         79 . An assay system for use in a cancer assay of a test sample, comprising:
 a test surface; and   a plurality of capture molecules immobilized directly or indirectly on the test surface, wherein the plurality of capture molecules are selected from a group of capture molecules specific for RNA, proteins, and/or cDNA corresponding to a biomarker panel comprising at least five biomarkers selected from the group consisting of the genes CDC45, CENPI, CLSPN, ERCC6L, EXO1, NCAPG, BUB1B, CDK1, E2F7, GSG2, NUSAP1, RAD51, and RRM2, wherein at least three of the at least five biomarkers are selected from CDC45, CENPI, CLSPN, ERCC6L, EXO1, NCAPG, and wherein an expression level of the biomarker panel in the sample is obtainable by measuring expression of each biomarker of the biomarker panel in the sample.   
     
     
         80 . The assay system of  claim 79 , wherein the test surface is selected from the group consisting of a plate, a microarray plate, microbeads, a capture surface, and a test strip. 
     
     
         81 . The assay system of  claim 79 , wherein the biomarker panel comprises CDC45. 
     
     
         82 . The assay system of  claim 79 , wherein the biomarker panel comprises CDC45 and NCAPG. 
     
     
         83 . The assay system of  claim 79 , wherein the biomarker panel comprises CDC45, NCAPG, and CLSPN. 
     
     
         84 . The assay system of  claim 79 , wherein the biomarker panel comprises at least four biomarkers selected from CDC45, CENPI, CLSPN, ERCC6L, EXO1, NCAPG. 
     
     
         85 . The assay system of  claim 79 , wherein the biomarker panel comprises at least five biomarkers selected from CDC45, CENPI, CLSPN, ERCC6L, EXO1, NCAPG. 
     
     
         86 . The assay system of  claim 79 , wherein the biomarker panel comprises CDC45, CENPI, CLSPN, ERCC6L, EXO1, NCAPG. 
     
     
         87 . The assay system of  claim 79 , wherein the biomarker panel comprises CDC45, CENPI, CLSPN, ERCC6L, EXO1, NCAPG, BUB1B, CDK1, NUSAP1, RAD51, and RRM2. 
     
     
         88 . The assay system of  claim 79 , further comprising oligonucleotides specific for one or more housekeeping genes for normalizing the expression level of the biomarker panel. 
     
     
         89 . A method for treating prostate cancer in a subject, comprising:
 (a) obtaining a sample derived from prostate gland tissue wherein the sample is obtained from a prostate biopsy, a surgically-excised prostate tissue, circulating cells, or portions of cells from the subject;   (b) measuring expression of a biomarker panel in the sample, the biomarker panel comprising at least five biomarkers selected from the group consisting of the genes CDC45, CENPI, CLSPN, ERCC6L, EXO1, NCAPG, BUB1B, CDK1, E2F7, GSG2, NUSAP1, RAD51, and RRM2, wherein at least three of the at least five biomarkers are selected from CDC45, CENPI, CLSPN, ERCC6L, EXO1, NCAPG;   (c) calculating a test value based on the expression of the biomarker panel;   (d) comparing the test value to a threshold index value; and   (e) administering to the subject active surveillance when the test value is less than the threshold index value, and administering to the subject one or more of hormonal therapy, chemotherapy, immunotherapy, radiation therapy, cryotherapy, or surgery when the test value is equal to or greater than the threshold index value.