Background: Survival for patients with castration-resistant prostate cancer is highly variable. We assessed the effectiveness of a whole-blood RNA transcript-based model as a prognostic biomarker in castration-resistant prostate cancer.
Methods: Peripheral blood was prospectively collected from 62 men with castration-resistant prostate cancer on various treatment regimens who were enrolled in a training set at the Dana-Farber Cancer Institute (Boston, MA, USA) from August, 2006, to June, 2008, and from 140 patients with castration-resistant prostate cancer in a validation set from Memorial Sloan-Kettering Cancer Center (New York, NY, USA) from August, 2006, to February, 2009. A panel of 168 inflammation-related and prostate cancer-related genes was assessed with optimised quantitative PCR to assess biomarkers predictive of survival.
Findings: A six-gene model (consisting of ABL2, SEMA4D, ITGAL, and C1QA, TIMP1, CDKN1A) separated patients with castration-resistant prostate cancer into two risk groups: a low-risk group with a median survival of more than 34·9 months (median survival was not reached) and a high-risk group with a median survival of 7·8 months (95% CI 1·8-13·9; p<0·0001). The prognostic utility of the six-gene model was validated in an independent cohort. This model was associated with a significantly higher area under the curve compared with a clinicopathological model (0·90 [95% CI 0·78-0·96] vs 0·65 [0·52-0·78]; p=0·0067).
Interpretation: Transcriptional profiling of whole blood yields crucial prognostic information about men with castration-resistant prostate cancer. The six-gene model suggests possible dysregulation of the immune system, a finding that warrants further study.
Funding: Source MDX.
Written by:
Ross RW, Galsky MD, Scher HI, Magidson J, Wassmann K, Lee GS, Katz L, Subudhi SK, Anand A, Fleisher M, Kantoff PW, Oh WK Are you the author?
Division of Solid Tumor Oncology, Department of Medicine, Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA
Reference: Lancet Oncol. 2012 Oct 8. pii: S1470-2045(12)70263-2. [Epub ahead of print]
doi: 10.1016/S1470-2045(12)70263-2.
PubMed Abstract
PMID: 23059047
