title: Prognostic value of an RNA expression signature derived from cell cycle proliferation genes in patients with prostate cancer: a retrospective study.
abstract: 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.
  
  
  RESULTS
  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 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, p=6·1×10(-22)) and the final multivariate analysis (2·57, 1·93-3·43; p=8·2×10(-11)), and was stronger than all other prognostic factors, although PSA concentration also added useful information. Heterogeneity in the hazard ratio for the CCP score was not noted in any case for any clinical variables.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  Cancer Research UK, Queen Mary University of London, Orchid Appeal, US National Institutes of Health, and Koch Foundation.
authors.affiliation: Cancer Research UK Centre of Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventive Medicine, St Bartholomew's Medical School, Queen Mary University of London, London, UK. j.cuzick@qmul.ac.uk
authors.forename: Jack
authors.initials: J
authors.lastname: Cuzick
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Swanson
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Fisher
authors.forename: Arthur R
authors.initials: AR
authors.lastname: Brothman
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Berney
authors.forename: Julia E
authors.initials: JE
authors.lastname: Reid
authors.forename: David
authors.initials: D
authors.lastname: Mesher
authors.forename: V O
authors.initials: VO
authors.lastname: Speights
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Stankiewicz
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Foster
authors.forename: Henrik
authors.initials: H
authors.lastname: Møller
authors.forename: Peter
authors.initials: P
authors.lastname: Scardino
authors.forename: Jorja D
authors.initials: JD
authors.lastname: Warren
authors.forename: Jimmy
authors.initials: J
authors.lastname: Park
authors.forename: Adib
authors.initials: A
authors.lastname: Younus
authors.forename: Darl D
authors.initials: DD
authors.lastname: Flake
authors.forename: Susanne
authors.initials: S
authors.lastname: Wagner
authors.forename: Alexander
authors.initials: A
authors.lastname: Gutin
authors.forename: Jerry S
authors.initials: JS
authors.lastname: Lanchbury
authors.forename: Steven
authors.initials: S
authors.lastname: Stone
mesh_terms: D000368:Aged; D020869:Gene Expression Profiling; D018816:Genes, cdc; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000601:surgery; D012313:RNA / Q000235:genetics*; D012189:Retrospective Studies
chemical_list: D012313:RNA