Prognostic value of an RNA expression signature derived from cell cycle proliferation genes in patients with prostate cancer: a retrospective study

作者：Jack M. Cuzick, Gregory P. Swanson, Gabrielle Fisher, Arthur R. Brothman, Daniel Maurice Berney, Julia Reid, David Mesher, V. O. Speights, Elzbieta Stankiewicz, Christopher S. Foster, Henrik Møller, Peter T. Scardino, Jorja D Warren, Jimmy Park, Adib Younus, Darl D. Flake, Susanne Wagner, Alexander Gutin, Jerry S. S. Lanchbury, Steven Stone · 发表于：The Lancet Oncology · 年份：2011 · DOI：10.1016/s1470-2045(10)70295-3 · 被引用次数：821 · 研究领域：Prostate Cancer Treatment and Research、Prostate Cancer Diagnosis and Treatment、Cancer Immunotherapy and Biomarkers

BACKGROUND: Optimum management of clinically localised prostate cancer presents unique challenges because of the highly variable and often indolent natural history of the disease. To predict disease aggressiveness, clinicians combine clinical variables to create prognostic models, but the models have limited accuracy. We assessed the prognostic value of a predefined cell cycle progression (CCP) score in two cohorts of patients with prostate cancer. METHODS: We measured the expression of 31 genes involved in CCP with quantitative RT-PCR on RNA extracted from formalin-fixed paraffin-embedded tumour samples, and created a predefined score and assessed its usefulness in the prediction of disease outcome. The signature was assessed retrospectively in a cohort of patients from the USA who had undergone radical prostatectomy, and in a cohort of randomly selected men with clinically localised prostate cancer diagnosed by use of a transurethral resection of the prostate (TURP) in the UK who were managed conservatively. The primary endpoint was time to biochemical recurrence for the cohort of patients who had radical prostatectomy, and time to death from prostate cancer for the TURP cohort. FINDINGS: After prostatectomy, the CCP score was useful for predicting biochemical recurrence in the univariate analysis (hazard ratio for a 1-unit change [doubling] in CCP 1·89; 95% CI 1·54-2·31; p=5·6×10(-9)) and the best multivariate analysis (1·77, 1·40-2·22; p=4·3×10(-6)). In the best predictiv...