Ras 相关结构域家族 1A：复发性非肌肉浸润性膀胱癌有前途的预后标志物。
Ras association domain family 1A: a promising prognostic marker in recurrent nonmuscle invasive bladder cancer.
机构信息
Department of Urology, College of Medicine, Chungbuk National University, Cheongju, Korea.
出版信息
Clin Genitourin Cancer. 2012 Jun;10(2):114-20. doi: 10.1016/j.clgc.2011.12.003. Epub 2012 Feb 28.
UNLABELLED
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.
INTRODUCTION
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.
MATERIALS AND 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.
目的
本研究旨在探讨 RASSF1A 甲基化作为膀胱癌预后标志物的价值。采用甲基化特异性 PCR 检测 301 例原发性膀胱癌组织中 RASSF1A 的超甲基化。在复发性非肌层浸润性膀胱癌（NMIBC）患者中，RASSF1A 甲基化被确定为癌症进展的独立预测因子。
引言
启动子 CpG 岛的异常甲基化是肿瘤抑制基因和肿瘤相关基因失活的重要机制。Ras 相关结构域家族 1A（RASSF1A）启动子的高甲基化与膀胱癌（BC）相关，但它的预后价值尚不清楚。本研究旨在探讨 RASSF1A 甲基化为 BC 患者的预后标志物的价值。
材料与方法
从 301 例膀胱癌患者中获得原发性膀胱癌组织，包括 186 例非肌层浸润性膀胱癌（NMIBC）和 115 例肌层浸润性膀胱癌（MIBC）。采用甲基化特异性聚合酶链反应（MS-PCR）检测 RASSF1A 超甲基化。通过 Kaplan-Meier 和多变量 Cox 回归分析评估 RASSF1A 超甲基化与临床病理特征的关系及其对预后的意义。
结果
RASSF1A 启动子超甲基化在 33.6%的 BC 中检测到，在 MIBC（46.1%）中比在 NMIBC（25.8%）中更常见（P<0.001）。在 NMIBC 中，RASSF1A 甲基化与晚期肿瘤分期（P=0.026）和高级别（P<0.001）相关。在复发性 NMIBC 患者中，RASSF1A 甲基化与 Kaplan-Meier 分析中的较短无进展时间相关（对数秩检验；P=0.004），并通过多变量 Cox 回归分析被确定为癌症进展的独立预测因子（风险比[HR]，8.559；P=0.014）。
结论
我们的结果表明，RASSF1A 甲基化可能是复发性 NMIBC 患者的潜在预后标志物。
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