A whole-blood RNA transcript-based prognostic model in men with castration-resistant prostate cancer: a prospective study

Robert W Ross MD a b †, Matthew D Galsky MD c †, Prof Howard I Scher MD d e, Jay Magidson PhD f, Karl Wassmann MBA g, Gwo-Shu Mary Lee PhD a b, Leah Katz MD a b, Sumit K Subudhi MD d e, Aseem Anand MD d e, Martin Fleisher PhD h, Prof Philip W Kantoff MD a b, Prof William K Oh MD c

Summary

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 0="0" a="a" an="an" area="area" associated="associated" ci="ci" clinicopathological="clinicopathological" cohort.="cohort." compared="compared" curve="curve" higher="higher" i="i" in="in" independent="independent" model="model" of="of" prognostic="prognostic" significantly="significantly" six-gene="six-gene" the="the" this="this" under="under" utility="utility" validated="validated" was="was" with="with">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.