背景:启动子区域肿瘤细胞中CpG岛的异常甲基化是非小细胞肺癌(NSCLC)肿瘤发生的关键事件,并且可以成为NSCLC患者的潜在诊断生物标志物。本研究系统定量地综述了CDH13甲基化在NSCLC及其亚群中的诊断能力。通过搜索PubMed确定了符合条件的研究,WebofScience,Cochrane图书馆和Embase。通过荟萃分析方法计算肺癌组织与正常对照中CDH13启动子甲基化的合并几率。同时,我们从TCGA和GEO数据库下载并分析了4个独立的非小细胞肺癌DNA甲基化数据集,以验证荟萃分析的结果.结果:13项研究,本荟萃分析包括1850个样本.在固定效应模型下,与对照组相比,癌组织中CDH13启动子甲基化的合并比值比为7.41(95%CI:5.34至10.29,P<0.00001)。在验证阶段,分析了来自TCGA的126个配对样品,CDH13的CpG岛的6个CpG位点中的5个在肺腺癌组织中被显着高甲基化,但在鳞状细胞癌组织中6个CpG位点均未被高甲基化。和谐地,其他三个数据集的结果,随后从由568个肿瘤和256个正常组织组成的GEO数据库中获得,还包括来自TCGA数据集的数据。结论:合并数据显示CDH13启动子的甲基化状态与肺腺癌密切相关。CDH13甲基化状态可能是诊断肺腺癌的有希望的诊断生物标志物。
Background: Aberrant methylation of CpG islands in tumor cells in promoter regions is a critical event in non-small cell lung carcinoma (NSCLC) tumorigenesis and can be a potential diagnostic biomarker for NSCLC patients. The present study systemically and quantitatively reviewed the diagnostic ability of
CDH13 methylation in NSCLC as well as in its subsets. Eligible studies were identified through searching PubMed, Web of Science, Cochrane Library and Embase. The pooled odds of
CDH13 promoter methylation in lung cancer tissues versus normal controls were calculated by meta-analysis method. Simultaneously, four independent DNA methylation datasets of NSCLC from TCGA and GEO database were downloaded and analyzed to validate the results from meta-analysis. Results: Thirteen studies, including 1850 samples were included in this meta-analysis. The pooled odds ratio of
CDH13 promoter methylation in cancer tissues was 7.41 (95% CI: 5.34 to 10.29, P < 0.00001) compared with that in controls under fixed-effect model. In validation stage, 126 paired samples from TCGA were analyzed and 5 out of the 6 CpG sites in the CpG island of
CDH13 were significantly hypermethylated in lung adenocarcinoma tissues but none of the 6 CpG sites was hypermethylated in squamous cell carcinoma tissues. Concordantly, the results from other three datasets, which were subsequently obtained from GEO database consisting of 568 tumors and 256 normal tissues, also consisted with those from TCGA dataset. Conclusion: The pooled data showed that the methylation status of the
CDH13 promoter is strongly associated with lung adenocarcinoma. The CDH13 methylation status could be a promising diagnostic biomarker for diagnosis of lung adenocarcinoma.