title: Prognostic value of a cell cycle progression signature for prostate cancer death in a conservatively managed needle biopsy cohort.
abstract: BACKGROUND
  The natural history of prostate cancer is highly variable and it is difficult to predict. We showed previously that a cell cycle progression (CCP) score was a robust predictor of outcome in a conservatively managed cohort diagnosed by transurethral resection of the prostate. A greater need is to predict outcome in patients diagnosed by needle biopsy.
  
  
  METHODS
  Total RNA was extracted from paraffin specimens. A CCP score was calculated from expression levels of 31 genes. Clinical variables consisted of centrally re-reviewed Gleason score, baseline prostate-specific antigen level, age, clinical stage, and extent of disease. The primary endpoint was death from prostate cancer.
  
  
  RESULTS
  In univariate analysis (n=349), the hazard ratio (HR) for death from prostate cancer was 2.02 (95% CI (1.62, 2.53), P<10(-9)) for a one-unit increase in CCP score. The CCP score was only weakly correlated with standard prognostic factors and in a multivariate analysis, CCP score dominated (HR for one-unit increase=1.65, 95% CI (1.31, 2.09), P=3 × 10(-5)), with Gleason score (P=5 × 10(-4)) and prostate-specific antigen (PSA) (P=0.017) providing significant additional contributions.
  
  
  CONCLUSIONS
  For conservatively managed patients, the CCP score is the strongest independent predictor of cancer death outcome yet described and may prove valuable in managing clinically localised prostate cancer.
authors.affiliation: Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary, University of London, Charterhouse Square, London EC1 M 6BQ, UK. j.cuzick@qmul.ac.uk
authors.forename: J
authors.initials: J
authors.lastname: Cuzick
authors.forename: D M
authors.initials: DM
authors.lastname: Berney
authors.forename: G
authors.initials: G
authors.lastname: Fisher
authors.forename: D
authors.initials: D
authors.lastname: Mesher
authors.forename: H
authors.initials: H
authors.lastname: Møller
authors.forename: J E
authors.initials: JE
authors.lastname: Reid
authors.forename: M
authors.initials: M
authors.lastname: Perry
authors.forename: J
authors.initials: J
authors.lastname: Park
authors.forename: A
authors.initials: A
authors.lastname: Younus
authors.forename: A
authors.initials: A
authors.lastname: Gutin
authors.forename: C S
authors.initials: CS
authors.lastname: Foster
authors.forename: P
authors.initials: P
authors.lastname: Scardino
authors.forename: J S
authors.initials: JS
authors.lastname: Lanchbury
authors.forename: S
authors.initials: S
authors.lastname: Stone
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D000368:Aged; D001707:Biopsy, Needle; D002453:Cell Cycle; D015331:Cohort Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen; D011471:Prostatic Neoplasms / Q000097:blood / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D020728:Transurethral Resection of Prostate
chemical_list: D017430:Prostate-Specific Antigen