1. State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai 200433, China;
2. Department of Cardiothoracic Surgery, Huashan Hospital, Fudan University, Shanghai 200032, China;
3. Department of Chest Surgery, Shanghai Pulmonary Hospital, Shanghai 200433, China.
4. Department of Bioengineering, University of California at San Diego, 9500 Gilman Drive, MC0412, La Jolla, CA 92093-0412.
* co-first author
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.
Keywords: CDH13, DNA methylation, Non-small cell lung cancer, NSCLC, Diagnosis, Adenocarcinoma, Biomarker.