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

被引:609
作者
Cuzick, Jack [1 ]
Swanson, Gregory P. [2 ,3 ,4 ]
Fisher, Gabrielle [1 ]
Brothman, Arthur R. [5 ,6 ,7 ]
Berney, Daniel M. [8 ]
Reid, Julia E. [9 ]
Mesher, David [1 ]
Speights, V. O. [10 ]
Stankiewicz, Elzbieta [8 ]
Foster, Christopher S. [11 ]
Moller, Henrik [12 ]
Scardino, Peter [13 ]
Warren, Jorja D. [9 ]
Park, Jimmy [9 ]
Younus, Adib [9 ]
Flake, Dart D., II [9 ]
Wagner, Susanne [9 ]
Gutin, Alexander [9 ]
Lanchbury, Jerry S. [9 ]
Stone, Steven [9 ]
机构
[1] Queen Mary Univ London, St Bartholomews Med Sch, Wolfson Inst Prevent Med, Canc Res UK Ctr Epidemiol Math & Stat, London EC1M 6BQ, England
[2] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiat Oncol, San Antonio, TX 78229 USA
[3] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX 78229 USA
[4] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA
[5] Univ Utah, Sch Med, Dept Pediat, Salt Lake City, UT USA
[6] Univ Utah, Sch Med, Dept Human Genet, Salt Lake City, UT USA
[7] Univ Utah, Sch Med, Dept Pathol, Salt Lake City, UT USA
[8] Queen Mary Univ London, Barts & London Sch Med & Dent, Ctr Mol Oncol & Imaging, London EC1M 6BQ, England
[9] Myriad Genet, Salt Lake City, UT USA
[10] Texas A&M Sch Med, Scott & White Clin, Dept Pathol, Temple, TX USA
[11] Liverpool Univ Hosp, Dept Cellular Pathol & Mol Genet, Liverpool, Merseyside, England
[12] Kings Coll London, Thames Canc Registry, London WC2R 2LS, England
[13] Mem Sloan Kettering Canc Ctr, Dept Urol, New York, NY 10021 USA
基金
美国国家卫生研究院;
关键词
RADICAL PROSTATECTOMY; BREAST-CANCER; SURVIVAL; PROBABILITY; RECURRENCE; MEN; ADENOCARCINOMA; IDENTIFICATION; MORTALITY; FAILURE;
D O I
10.1016/S1470-2045(10)70295-3
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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=5.6x10(-9)) and the best multivariate analysis (1 77, 1.40-2.22; p=4.3x10(-6)). In the best predictive model (final multivariate analysis), the CCP score and prostate-specific antigen (PSA) concentration were the most important variables and were more significant than any other clinical variable. In the TURP cohort, the CCP score was the most important variable for prediction of time to death from prostate cancer in both univariate analysis (2.92, 2.38-3.57, p6.1x10(-22)) and the final multivariate analysis (2.57, 1.93-3.43; p=8.2x10(-11)), and was stronger than all other prognostic factors, although P SA concentration also added useful information. Heterogeneity in the hazard ratio for the CCP score was not noted in any case for any clinical variables. Interpretation The results of this study provide strong evidence that the CCP score is a robust prognostic marker, which, after additional validation, could have an essential role in determining the appropriate treatment for patients with prostate cancer.
引用
收藏
页码:245 / 255
页数:11
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