Yuan Xiaolong, Xu Jifei, Fang Weiyang, Zhao Zhenfeng, Wang Fan, Tong Zhuting
Department of Radiotherapy, The First Affiliated Hospital of Anhui Medical University , Hefei, People's Republic of China .
Genet Test Mol Biomarkers. 2017 Apr;21(4):213-221. doi: 10.1089/gtmb.2016.0284. Epub 2017 Feb 23.
Several previous studies have suggested that MGMT promoter methylation is significantly associated with gastric cancer, but the results were not consistent. Hence, we conducted a systematic meta-analysis to explore the potential correlation of MGMT promoter methylation with gastric cancer and its clinicopathologic characteristics.
Searches of PubMed, EMBASE, Web of Science, Cochrane Library, and Chinese National Knowledge Infrastructure (CNKI) literature databases were conducted to identify relevant studies published in English or Chinese before July 1, 2016. The meta-analysis was performed using Stata 12.0 software. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the association between MGMT promoter methylation and gastric cancer. We also conducted a subgroup analysis and metaregression to explore sources of heterogeneity.
We identified 12 articles that met the inclusion criteria. The 12 articles described 14 studies that included 1571 tumor tissues and 1243 controls. The meta-analysis results demonstrated that the frequency of MGMT promoter methylation was higher in gastric cancer tissues compared with adjacent tissues and normal tissues (OR = 4.06, 95% CI: 2.55-6.46, p < 0.001; OR = 8.85, 95% CI: 1.15-68.23, p = 0.036; respectively). An assessment of the correlation between MGMT promoter methylation and clinicopathological characteristics indicated that MGMT promoter hypermethylation was significantly associated with tumor-node-metastasis stage, lymph node metastasis, and distant metastasis (OR = 2.11, 95% CI: 1.18-3.75, p = 0.011; OR = 1.99, 95% CI: 1.47-2.68, p < 0.001; and OR = 3.60, 95% CI: 2.17-5.95, p < 0.001; respectively).
Our findings provide evidence that MGMT promoter methylation could play an important role in gastric carcinogenesis and may serve as an important biomarker for gastric cancer progression.
此前多项研究表明O6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)启动子甲基化与胃癌显著相关,但结果并不一致。因此,我们进行了一项系统的荟萃分析,以探讨MGMT启动子甲基化与胃癌及其临床病理特征之间的潜在相关性。
检索了PubMed、EMBASE、科学网、Cochrane图书馆和中国知网(CNKI)文献数据库,以识别2016年7月1日前发表的英文或中文相关研究。使用Stata 12.0软件进行荟萃分析。计算比值比(OR)和95%置信区间(CI),以评估MGMT启动子甲基化与胃癌之间的关联。我们还进行了亚组分析和Meta回归,以探讨异质性来源。
我们确定了12篇符合纳入标准的文章。这12篇文章描述了14项研究,包括1571个肿瘤组织和1243个对照。荟萃分析结果表明,与癌旁组织和正常组织相比,胃癌组织中MGMT启动子甲基化的频率更高(OR = 4.06,95%CI:2.55 - 6.46,p < 0.001;OR = 8.85,95%CI:1.15 - 68.23,p = 0.036;分别)。对MGMT启动子甲基化与临床病理特征之间相关性的评估表明,MGMT启动子高甲基化与肿瘤-淋巴结-转移分期、淋巴结转移和远处转移显著相关(OR = 2.11,95%CI:1.18 - 3.75,p = 0.011;OR = 1.99,95%CI:1.47 - 2.68,p < 0.001;以及OR = 3.60,95%CI:2.17 - 5.95,p < 0.001;分别)。
我们的研究结果提供了证据,表明MGMT启动子甲基化可能在胃癌发生中起重要作用,并可能作为胃癌进展的重要生物标志物。