Clinicopathological significance of DAPK promoter methylation in non-small-cell lung cancer: a systematic review and meta-analysis

Yan Zhang,1,* Jiang Wu,1,* Gui Huang,1 Shouming Xu2 1Department of Pathology, Huaihe Hospital, Henan University; 2School of Life Sciences, Henan University, Kaifeng 475004, People’s Republic of China *These authors contributed equally to this work Background: Lung carcinogenesis is related to silencing of tumor suppressor genes and activation of oncogenes. The aim was to investigate the significance of death-associated protein kinase (DAPK) methylation in non-small-cell lung cancer (NSCLC) through a meta-analysis.Methods: A detailed literature search was made in PubMed, Embase, and Web of Science databases. All analysis was performed with Review Manager 5.2. Results: In total, 28 studies with a total of 2,148 patients were involved. The frequency of DAPK promoter hypermethylation was 40.50% in NSCLC, significantly higher than in non-malignant lung tissue; the pooled OR was 5.69, P<0.00001. Additionally, DAPK promoter hypermethylation was significantly correlated with poor overall survival in patients with NSCLC. However, there was no significant difference found while comparing the rate of DAPK promoter hypermethylation in adenocarcinoma and squamous cell cancer. The rate of DAPK promoter hypermethylation was similar between stage III/IV and stage I/II. In addition, the data showed that DAPK promoter hypermethylation was not associated with smoking behavior in patients with NSCLC.Conclusion: DAPK promoter hypermethylation is correlated with risk of NSCLC and is a potential biomarker for prediction of poor prognosis in patients with NSCLC. Keywords: DAPK, NSCLC, biomarker, methylation, adenocarcinoma, squamous cell cancer, drug targe