DAPK promoter hypermethylation in tissues and body fluids of oral precancer patients

Death-associated protein kinase (DAPK) has been suggested as a tumor suppressor gene. A high frequency of DAPK promoter hypermethylation has been noted in head and neck cancers and other solid tumors, and it has been used as a tumor marker in molecular detection strategies. Our aim was to examine DAPK promoter hypermethylation in tissue, blood, and salivary rinse samples of oral precancer patients (OPs) and to explore the potential role in oral carcinogenesis. DAPK hypermethylation was analyzed in 77 OPs and 32 oral squamous cell carcinomas (OSCCs) by real-time quantitative methylation-specific PCR (QMSP). We compared the hypermethylation expression between two groups and analyzed the associations with clinicopathologic parameters. The promoter hypermethylation frequency of DAPK in tissue (46.9%) and blood (52.2%) of OSCCs was significantly higher than those in OPs (19.5%, P = 0.004; 22.4%, P = 0.007, respectively). DAPK promoter hypermethylation expression in blood was correlated with its expression in tissue (r = 0.49, P < 0.000). The OP patients who smoked more than 20 years were found 40.0% tissue DAPK hypermethylation in contrast with 10.7% tissue DAPK hypermethylation in the patients whose smoking duration ≦20 years (P = 0.010). Our results suggest that DAPK hypermethylation is an early event in oral carcinogenesis and blood DAPK hypermethylation might be a potential minimal invasive biomarker for OSCC early detection.