title: Prognostic utility of cell cycle progression score in men with prostate cancer after primary external beam radiation therapy.
abstract: OBJECTIVE
  To evaluate the prognostic utility of the cell cycle progression (CCP) score, a RNA signature based on the average expression level of 31 CCP genes, for predicting biochemical recurrence (BCR) in men with prostate cancer treated with external beam radiation therapy (EBRT) as their primary curative therapy.
  
  
  METHODS
  The CCP score was derived retrospectively from diagnostic biopsy specimens of men diagnosed with prostate cancer from 1991 to 2006 (n=141). All patients were treated with definitive EBRT; approximately half of the cohort was African American. Outcome was time from EBRT to BCR using the Phoenix definition. Median follow-up for patients without BCR was 4.8 years. Association with outcome was evaluated by Cox proportional hazards survival analysis and likelihood ratio tests.
  
  
  RESULTS
  Of 141 patients, 19 (13%) had BCR. The median CCP score for patient samples was 0.12. In univariable analysis, CCP score significantly predicted BCR (P=.0017). The hazard ratio for BCR was 2.55 for 1-unit increase in CCP score (equivalent to a doubling of gene expression). In a multivariable analysis that included Gleason score, prostate-specific antigen, percent positive cores, and androgen deprivation therapy, the hazard ratio for CCP changed only marginally and remained significant (P=.034), indicating that CCP provides prognostic information that is not provided by standard clinical parameters. With 10-year censoring, the CCP score was associated with prostate cancer-specific mortality (P=.013). There was no evidence for interaction between CCP and any clinical variable, including ethnicity.
  
  
  CONCLUSIONS
  Among men treated with EBRT, the CCP score significantly predicted outcome and provided greater prognostic information than was available with clinical parameters. If validated in a larger cohort, CCP score could identify high-risk men undergoing EBRT who may need more aggressive therapy.
authors.affiliation: Department of Surgery, Durham VA Medical Center, Durham, North Carolina, USA. steve.freedland@duke.edu
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Freedland
authors.forename: Leah
authors.initials: L
authors.lastname: Gerber
authors.forename: Julia
authors.initials: J
authors.lastname: Reid
authors.forename: William
authors.initials: W
authors.lastname: Welbourn
authors.forename: Eliso
authors.initials: E
authors.lastname: Tikishvili
authors.forename: Jimmy
authors.initials: J
authors.lastname: Park
authors.forename: Adib
authors.initials: A
authors.lastname: Younus
authors.forename: Alexander
authors.initials: A
authors.lastname: Gutin
authors.forename: Zaina
authors.initials: Z
authors.lastname: Sangale
authors.forename: Jerry S
authors.initials: JS
authors.lastname: Lanchbury
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Salama
authors.forename: Steven
authors.initials: S
authors.lastname: Stone
mesh_terms: D000368:Aged; D002453:Cell Cycle / Q000235:genetics; D018816:Genes, cdc; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000208:ethnology / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy; D012333:RNA, Messenger / Q000032:analysis*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D012333:RNA, Messenger; D017430:Prostate-Specific Antigen