Hypermethylation of Death-Associated Protein Kinase (DAPK1) and its association with oral carcinogenesis - An experimental and meta-analysis study

Objectives: The value of abnormal DNA methylation of DAPK1 promoter and its association with various cancers have been suggested in the literature. To establish the significance of DNA methylation of DAPK1 promoter in oral squamous cell carcinoma (OSCC), we a) performed a case-control study, b) evaluated published data for its utility in the diagnosis and prognosis of OSCC and c) identified the association of DAPK1 gene expression with promoter DNA methylation status. Design: Bisulfite gene sequencing of DAPK1 promoter region was performed on non-malignant and malignant oral samples. Further, using a systematic search, 330 publications were retrieved from PubMed, Scopus, and Google Scholar and 11 relevant articles were identified. Results: Significant association of DAPK1 promoter methylation with OSCC (p < 0.0001) was observed in the case-control study. The studies chosen for meta-analysis showed prognostic and predictive significance of DAPK1 gene promoter, despite defined inconsistencies in few studies. Overall, we obtained a statistically significant (pvalue < 0.001) association for both sensitivity and specificity of DAPK1 DNA promoter methylation in oral cancer cases, without publication bias. Conclusion: DNA hypermethylation of DAPK1 gene promoter is a promising biomarker for OSCC prediction/ prognostics and suggests further validation in large distinct cohorts to facilitate translation to clinics.