METHYLATION PROFILING OF DAPK1, LRPPRC, RAB6C, AND ZNF471 IN SALIVA AND TISSUES AS NOVEL EPIGENETIC MARKERS OF ORAL SQUAMOUS CELL CARCINOMA

Background Despite rapid progress in the diagnosis and treatment of oral squamous cell carcinoma (OSCC), the survival rates remain poor. Early identification of premalignant lesions is critical in reducing mortality. Epigenetic changes, such as aberrant DNA methylation resulting in altered gene expression, contribute to oral carcinogenesis. Objective To identify aberrantly methylated genes in saliva and tissue of OSCC patients as novel biomarkers of patients’ prognosis. Methods Genome-wide methylation changes were identified by differential methylation hybridization microarray. The results were compared against datasets from TCGA-HNSCC. Promoter sequences of DAPK1, LRPPRC, RAB6C, and ZNF471 were validated by bisulfite genome sequencing. The methylation status of these genes was tested in saliva and tissue specimens by targeted next-generation sequence. Results Promoter sequences of DAPK1, LRPPRC, RAB6C, and ZNF471 were significantly hypermethylated in tumors compared with matched normal tissue (P Conclusions Our data confirms that the methylation pattern of these candidate genes are significantly higher in premalignant and OSCC tissues and saliva. Thus, the methylation profiling of these candidate genes has the potential to serve as novel non-invasive markers of OSCC.