Abstract
BACKGROUND: Methylation represents the second hit in tumor development. In nasopharyngeal carcinoma (NPC), multiple tumor suppressor genes located on chromosome 9 under methylation. AIMS: This first case-control study aims to explore the methylation characteristics of DAPK, p16INK4α, p15INK4α, and p14ARF, individually and in combination, to evaluate their potential as promising biomarkers for nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: A total of 70 NPC biopsy samples and 60 non-cancerous swab samples were enrolled into the current study. Genomic DNA extraction, bisulfite modification, and methylation-specific PCR (MSP) were used to analyze methylation status. Statistical analyses, including odds ratio (OR) calculations and methylation index (MI) evaluation, were conducted to determine the association between methylation and nasopharyngeal carcinoma (NPC). RESULTS: Promoter hypermethylation was observed in 75.71%, 78.57%, 52.86%, and 87.14% of samples for DAPK, p16INK4α, p15INK4α, and p14ARF, respectively. A significant association between the methylation status of these candidate genes and nasopharyngeal carcinoma (NPC) was identified. The methylation of these genes significantly increased the risk of NPC compared to control samples (OR > 1). Based on the methylation index (MI), 100% of NPC samples showed methylation in at least one gene (MI ≥ 0.25). An MI ≥ 0.25 demonstrated a sensitivity of 100% and a specificity of 50%, highlighting its potential as a diagnostic marker. CONCLUSION: This study highlights the potential of DAPK, p16INK4α, p15INK4α, and p14ARF methylation as biomarkers for the diagnosis and early screening of nasopharyngeal carcinoma (NPC) in Vietnamese patients. The findings support the use of a composite methylation index as a sensitive biomarker for the early detection and screening of NPC.