Department of Urology, College of Medicine, Chungbuk National University, Cheongju, Chungbuk, South Korea.
Eur J Surg Oncol. 2012 Nov;38(11):1095-100. doi: 10.1016/j.ejso.2012.07.116. Epub 2012 Aug 9.
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).
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).
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.
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.
此前，我们报道了 RUNX3 甲基化与膀胱癌发展之间存在因果关系。因此，为了阐明其在肿瘤发生中的作用，本研究旨在确定 RUNX3 甲基化在非肌层浸润性膀胱癌（NMIBC）患者的正常邻近尿路上皮中的功能。
选择 55 例接受经尿道切除术（TUR）的患者的肿瘤组织和供体匹配的正常邻近组织进行研究，使用甲基化特异性聚合酶链反应（MS-PCR）评估 RUNX3 启动子甲基化。
NMIBC 患者的肿瘤样本中 RUNX3 启动子甲基化的发生率高于组织学正常尿路上皮（P=0.02）。正常邻近尿路上皮和肿瘤组织中 RUNX3 启动子的甲基化率分别为 47%和 69%。有趣的是，正常邻近尿路上皮中的 RUNX3 甲基化与肿瘤数量（P=0.022）和进展（P=0.035）相关。Kaplan-Meier 估计显示，正常尿路上皮中的 RUNX3 甲基化与 NMIBC 患者的进展时间（P=0.017）显著相关。将患者分为肿瘤和正常尿路上皮的“均甲基化”、“一个甲基化”和“无甲基化”组，在随访期间，“无甲基化”组无进展。多变量 Cox 回归分析表明，正常尿路上皮中的 RUNX3 甲基化[风险比（HR）：5.692，P=0.042]是进展的独立预测因子。
RUNX3 甲基化与从正常尿路上皮向膀胱癌的转变有关。更重要的是，TUR 治疗后的 NMIBC 患者正常邻近尿路上皮中的 RUNX3 甲基化可能预示着进展。
