title: RUNX3 methylation in normal surrounding urothelium of patients with non-muscle-invasive bladder cancer: potential role in the prediction of tumor progression.
abstract: OBJECTIVE
  Previously, we reported a causal relationship between RUNX3 methylation and bladder tumor development. Thus, in order to clarify its role in tumorigenesis, this study aims to identify the function of RUNX3 methylation in normal adjacent urothelium of patients with non-muscle invasive bladder cancer (NMIBC).
  
  
  METHODS
  Tumor tissue and donor-matched normal adjacent tissue from 55 patients who underwent transurethral resection (TUR) were selected for the study, and RUNX3 promoter methylation was assessed using methylation-specific polymerase chain reaction (MS-PCR).
  
  
  RESULTS
  RUNX3 promoter methylation occurred more frequently in tumor samples than in histologically normal urothelium in patients with NMIBC (P = 0.02). The methylation rates for the RUNX3 promoter in normal adjacent urothelium and tumor tissue were 47% and 69%, respectively. Interestingly, RUNX3 methylation in normal adjacent urothelium was associated with tumor number (P = 0.022) and progression (P = 0.035). Kaplan-Meier estimates revealed that RUNX3 methylation in normal urothelium showed a significant association with time to progression (P = 0.017) in NMIBC patients. Stratifying the patients into 'both methylation', 'one methylation' and 'no methylation' groups for tumors and normal urothelium revealed that no progression occurred in the 'no methylation' group during follow-up. Multivariate Cox regression analysis demonstrated that RUNX3 methylation in normal urothelium [hazards ratio (HR): 5.692, P = 0.042] was an independent predictor of progression.
  
  
  CONCLUSIONS
  RUNX3 methylation was associated with transition from normal urothelium to bladder tumor. More importantly, RUNX3 methylation in normal adjacent urothelium may predict progression in NMIBC patients who have undergone TUR.
authors.affiliation: Department of Urology, College of Medicine, Chungbuk National University, Cheongju, Chungbuk, South Korea.
authors.forename: P
authors.initials: P
authors.lastname: Jeong
authors.forename: B D
authors.initials: BD
authors.lastname: Min
authors.forename: Y S
authors.initials: YS
authors.lastname: Ha
authors.forename: P H
authors.initials: PH
authors.lastname: Song
authors.forename: I Y
authors.initials: IY
authors.lastname: Kim
authors.forename: K H
authors.initials: KH
authors.lastname: Ryu
authors.forename: J H
authors.initials: JH
authors.lastname: Kim
authors.forename: S J
authors.initials: SJ
authors.lastname: Yun
authors.forename: W J
authors.initials: WJ
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D050677:Core Binding Factor Alpha 3 Subunit / Q000378:metabolism*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008745:Methylation; D008875:Middle Aged; D011379:Prognosis; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology; D019459:Urothelium / Q000378:metabolism*; D055815:Young Adult
chemical_list: D050677:Core Binding Factor Alpha 3 Subunit