Department of Oncology, General Hospital, Jinan Command of the People's Liberation Army, Tianqiao District, Jinan 250031, China.
Carcinogenesis. 2011 Mar;32(3):411-6. doi: 10.1093/carcin/bgq266. Epub 2010 Dec 14.
Inactivation of the tumor suppressor gene RASSF1A through methylation of the CpG islands within its promoter region as a prognostic factor for survival in non-small cell lung carcinoma (NSCLC) remains controversial. A meta-analysis of published studies investigating the effects of RASSF1A methylation on both relapse-free survival (RFS) and overall survival (OS) among NSCLC patients was performed. A total of 2802 patients from 19 eligible studies were included in the systematic review and 17 studies were included in the meta-analysis. In all, 32.6% of NSCLC patients had the methylated RASSF1A allele. Four of these studies investigated the correlation between RASSF1A methylation and RFS using univariate analysis. The univariate estimate for RFS was 1.87 [95% confidence interval (CI): 1.41-2.49; P < 0.0001] with no evidence of significant heterogeneity. Thirteen studies undertook univariate analyses of RASSF1A methylation and OS and 12 undertook multivariate analyses of RASSF1A methylation and OS. The pooled hazard ratio (HR) estimate for OS was 1.52 (95% CI: 1.33-1.74; P < 0.0001) by univariate analysis and 1.34 (95% CI: 1.15-1.57; P < 0.0001) by multivariate analysis. No significant heterogeneity was detected. For stages I-II NSCLC, the meta-risk remained highly significant by both univariate (HR = 1.94; 95% CI: 1.54-2.44; P < 0.0001) and multivariate analysis (HR = 1.39; 95% CI: 1.02-1.90; P = 0.039). This study shows that RASSF1A methylation appears to be an independent prognostic factor for poor survival in surgically treated NSCLC. However, the present findings require confirmation though adequately designed prospective studies.
抑癌基因 RASSF1A 通过其启动子区域内 CpG 岛的甲基化失活被认为是非小细胞肺癌（NSCLC）患者生存的预后因素，但仍存在争议。本研究对探讨 RASSF1A 甲基化对 NSCLC 患者无复发生存（RFS）和总生存（OS）影响的已发表研究进行了荟萃分析。系统性综述共纳入了 19 项合格研究中的 2802 例患者，其中 17 项研究纳入荟萃分析。共有 32.6%的 NSCLC 患者存在 RASSF1A 甲基化等位基因。其中 4 项研究使用单变量分析探讨了 RASSF1A 甲基化与 RFS 的相关性。RFS 的单变量估计值为 1.87（95%置信区间：1.41-2.49；P<0.0001），且无明显异质性。13 项研究对 RASSF1A 甲基化与 OS 进行了单变量分析，12 项研究对 RASSF1A 甲基化与 OS 进行了多变量分析。OS 的单变量汇总风险比（HR）估计值为 1.52（95%置信区间：1.33-1.74；P<0.0001），多变量分析的 HR 估计值为 1.34（95%置信区间：1.15-1.57；P<0.0001）。未检测到明显的异质性。对于 I 期-II 期 NSCLC，单变量（HR=1.94；95%置信区间：1.54-2.44；P<0.0001）和多变量分析（HR=1.39；95%置信区间：1.02-1.90；P=0.039）的荟萃风险仍然具有高度显著性。本研究表明，RASSF1A 甲基化似乎是非手术治疗 NSCLC 患者不良生存的独立预后因素。然而，这些发现需要通过精心设计的前瞻性研究加以证实。
