A whole-blood RNA transcript-based prognostic model in men with castration-resistant prostate cancer: a prospective study
A partir d'échantillons sanguins prélevés sur des patients atteints d'un cancer de la prostate résistant à la castration et sur des patients atteints d'un cancer de la prostate sous surveillance active, ces deux études prospectives évaluent, du point de vue de la survie globale, la valeur pronostique de profils d'expression de gènes, l'un faisant appel à 9 gènes, l'autre à 6 gènes
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. 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. A six-gene model (consisting ofABL2, SEMA4D, ITGAL, andC1QA, 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]vs0·65 [0·52?0·78]; p=0·0067). 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. Source MDX.
The Lancet Oncology , résumé, 2011