A validated whole-blood RNA transcript-based prognostic model that predicts survival in men with castration-resistant prostate cancer.

Abstract

4516 Background: Survival for patients with castration resistant prostate cancer (CRPC) is highly variable. We developed a whole blood RNA transcript-based model as a prognostic biomarker in CRPC. Methods: Peripheral blood was collected from 62 men with CRPC in a training set and from 140 patients with CRPC in a validation set on various treatment regimens. A panel of 168 inflammation and prostate cancer-related genes was evaluated using optimized quantitative polymerase chain reaction to assess biomarkers predictive of survival. A 2-class proportional hazard model was developed from time of CRPC diagnosis and time of blood draw. Results: A 6-gene model (consisting of ABL2, SEMA4D, ITGAL, and C1QA, TIMP1, CDKN1A) separated CRPC patients into two classes: higher risk men who died within 2·2 years of developing CRPC and lower risk men who lived over 2·2 years (log rank p=0·00083). The results were similar regardless of the survival time definition (CRPC diagnosis versus blood draw) and did not depend on whether they received chemotherapy in addition to hormone treatment. The model successfully validated in an independent cohort of men with CRPC (p= 0.000001·7). Conclusions: Transcriptional profiling of whole blood yields critical prognostic information in men with CRPC independent of treatment. The 6-gene model suggests possible dysregulation of the immune system, a finding that warrants further study. This model may play an important role in patient counseling, in patient stratification for clinical trials, and potentially as a predictive biomarker for immune-based therapeutic strategies.