title: Ras association domain family 1A: a promising prognostic marker in recurrent nonmuscle invasive bladder cancer.
abstract: The aim of this study was to investigate the value of RASSF1A methylation as a prognostic marker in bladder cancer. RASSF1A hypermethylation from 301 specimens of primary BC tissue was assessed using methylation-specific PCR. Among patients with recurrent NMIBC, RASSF1A methylation was identified as an independent predictor of cancer progression.
  
  
  BACKGROUND
  Aberrant methylation of promoter CpG islands is an important inactivation mechanism of tumor suppressors and tumor-related genes. Ras association domain family 1A (RASSF1A) promoter hypermethylation was shown to be associated with bladder cancer (BC), but its prognostic value remains unclear. The aim of the present study was to investigate the value of RASSF1A methylation as a prognostic marker in BC.
  
  
  METHODS
  Primary BC tissues were obtained from 301 patients and included 186 specimens of nonmuscle invasive bladder cancer (NMIBC) and 115 specimens of muscle invasive bladder cancers (MIBC). RASSF1A hypermethylation was assessed using methylation-specific polymerase chain reaction (MS-PCR). The association between RASSF1A hypermethylation and clinicopathologic features, and the prognostic significance of RASSF1A hypermethylation were evaluated by Kaplan-Meier and multivariate Cox regression analyses.
  
  
  RESULTS
  RASSF1A promoter hypermethylation was detected in 33.6% of BCs and occurred more frequently in MIBC (46.1%) than in NMIBC (25.8%) (P < .001). In NMIBC, RASSF1A methylation was associated with advanced tumor stage (P = .026) and high grade (P < .001). Among patients with recurrent NMIBC, RASSF1A methylation was associated with shorter time to progression by Kaplan-Meier analysis (log-rank test; P = .004) and identified as an independent predictor of cancer progression by multivariate Cox regression analysis (hazard ratio [HR], 8.559; P = .014).
  
  
  CONCLUSIONS
  Our results suggest that methylated RASSF1A may be a potential prognostic marker in patients with recurrent NMIBC.
authors.affiliation: Department of Urology, College of Medicine, Chungbuk National University, Cheongju, Korea.
authors.forename: Ji Sang
authors.initials: JS
authors.lastname: Kim
authors.forename: Yunbyung
authors.initials: Y
authors.lastname: Chae
authors.forename: Yun-Sok
authors.initials: YS
authors.lastname: Ha
authors.forename: Isaac Yi
authors.initials: IY
authors.lastname: Kim
authors.forename: Seok Soo
authors.initials: SS
authors.lastname: Byun
authors.forename: Seok-Joong
authors.initials: SJ
authors.lastname: Yun
authors.forename: Wun-Jae
authors.initials: WJ
authors.lastname: Kim
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D002295:Carcinoma, Transitional Cell / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D002648:Child; D019175:DNA Methylation; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011379:Prognosis; D011401:Promoter Regions, Genetic; D016016:Proportional Hazards Models; D047368:Tumor Burden; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins