A six-gene panel that predicts survival in men with castration-resistant prostate cancer.

Abstract

4539 Background: Patients with castration-resistant prostate cancer (CRPC) represent a heterogeneous group with survival times ranging from several months to over eight years. Circulating tumor cell (CTC) number is prognostic for survival. While patients with unfavorable (5 or more cells per 7.5 ml blood) counts have inferior survival times, the presence of a low count (4 or less per 7.5 ml blood) does not distinguish the patients who will succumb early to their disease and those who will not. Therefore, we have developed a RNA-based assay to address this issue. Methods: 45 genes from whole blood were evaluated as potential candidates for predicting overall survival in patients. 102 patients with progressive CRPC were identified at Memorial Sloan-Kettering Cancer Center (MSKCC). Whole blood from these patients was collected in PAXgene blood RNA tubes at the time of progression, and RNA was isolated using a PAXgene blood RNA kit (Source MDx). Expression analysis was performed on these samples, and a predictive gene signature for survival time was developed from the L1 penalized partial likelihood derived from the proportional hazards model. Results: Six genes were found to be jointly predictive of survival time. The genes and their relative risk coefficient are presented in the table below. The predictive accuracy of the joint model, characterized by the concordance probability estimate, is equal to 0.71 (standard error = 0.03). Conclusions: We have identified a 6-gene panel that predicts survival in our cohort of patients with CRPC. This panel will require validation in another cohort. Gene BCL2 C1QB CAV2 CD82 GAS1 NFATC2 RR 0.07 -0.46 -0.03 0.01 0.04 0.30