RUNX3 methylation in normal surrounding urothelium of patients with non-muscle-invasive bladder cancer: Potential role in the prediction of tumor progression

Title
RUNX3 methylation in normal surrounding urothelium of patients with non-muscle-invasive bladder cancer: Potential role in the prediction of tumor progression
Author(s)
송필현정필두[정필두]민병달[민병달]하윤석[하윤석]김이삭[김이삭]류근호[류근호]김정현[김정현]윤석중[윤석중]김원재[김원재]
Keywords
DNA METHYLATION; EARLY EVENT; STAGE-TA; CARCINOMA; GENE; FIELD; INACTIVATION; EXPRESSION; PROMOTER; REVEALS
Issue Date
201211
Publisher
ELSEVIER SCI LTD
Citation
EJSO, v.38, no.11, pp.1095 - 1100
Abstract
Purpose: 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. (c) 2012 Elsevier Ltd. All rights reserved.
URI
http://hdl.handle.net/YU.REPOSITORY/26972http://dx.doi.org/10.1016/j.ejso.2012.07.116
ISSN
0748-7983
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의과대학 > 비뇨기과학교실 > Articles
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