Background: DNA promoter methylation of the tumor suppressor genes was one of the key mechanism for gene silence. The aim of this study is to investigate the difference of MGMT gene promoter methylation rate in tumor tissue and autologous controls (serum, normal lung tissue and bronchial lavage fluid) in patients with non-small cell lung cancer (NSCLC).
Methods: The databases of Medline, EMBSE, CNKI and Wanfang were searched for selection of published articles of MGMT gene promoter methylation and non-small cell lung carcinoma risk. The pooled odds ratio (OR) and percentage of MGMT for lung cancer tissue of NSCLC patients compared with normal lung tissue, plasma and the bronchial lavage fluid were pooled.
Results: 15 articles of association between MGMT gene promoter methylation and non small cell lung carcinoma risk were included in this meta-analysis. The combined results demonstrated the methylation rate of MGMT in NSCLC cancer tissue was 38% (95%CI: 23%-53%). For normal lung tissue, plasma and the bronchial lavage fluid were 16% (95%CI: 5%-27%), 23% (95%CI: 10%-34%) and 39% (95%CI: 23%-55%) respectively. The OR in cancer tissue was much higher than that in normal lung tissue and plasma odds ratio (OR) 3.98 (95%CI: 2.71-5.84, P<0.05) and OR 1.88 (95%CI: 1.16-3.05, P<0.05), but not in bronchial lavage fluid OR 2.05 (95%CI: 0.88-4.78, P>0.05).
Conclusions: Mehtylation rate in MGMT gene promoter of cancer tissue in NSCLC patients was much higher than that in normal lung tissue and plasma, which showed a close association between NSCLC cancer and MGMT gene promoter methylation.
背景与目的 抑癌基因启动子区域甲基化是基因失活的重要机制之一，本研究采用meta分析的方法探讨非小细胞肺癌（non-small cell lung cancer, NSCLC）患者癌组织与自身对照组织（血浆、正常肺组织及支气管灌洗液）MGMT基因启动子甲基化率有无差别。方法 计算机检索Medline 、EMBASE、CNKI及万方等数据库，收集公开发表的涉及MGMT基因启动子甲基化与NSCLC关系的临床研究。采用meta分析的方法比较NSCLC患者癌组织与正常自身对照组织中MGMT基因启动子甲基化率有无差别。结果 15篇文献符合纳入标准并纳入本研究，NSCLC患者肺癌组织中MGMT基因启动子甲基化率为38%（95%CI: 23%-53%）；NSCLC患者正常肺组织、血浆和支气管灌洗液中MGMT基因启动子甲基化率分别为16%（95%CI: 5%-27%）、23%（95%CI: 10%-34%）和39%（95%CI: 23%-55%）。与正常肺组织和血浆比较，肺癌中MGMT基因启动子甲基化率增高（OR=3.98, 95%CI: 2.71-5.84, P<0.05）（OR=1.88, 95%CI: 1.16-3.05, P<0.05），与支气管灌洗液比较差别无统计学意义（OR=2.05, 95%CI: 0.88-4.78, P>0.05）。结论 NSCLC患者肺癌组织中MGMT基因启动子甲基化率增高，该基因的启动子甲基化与肺癌的发生可能存在相关性。