Study on aberrant DNA hypermethylation in HNSCC

• Main Authors: Wei-Li Huang, 黃偉立
• Other Authors: Shou-Yen Kao, Prof.
• Format: Others
• Language: zh-TW
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/57928066603552128499

碩士 === 國立陽明大學 === 臨床牙醫學研究所 === 97 === Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Of HNSCC patients, recurrence and metastasis are common even after treatment and usually results in poor prognosis. Hypermethylation of CpG islands in promoter region of tumor suppressor genes is well-demonstrated in cancers and is under development to act as biomarkers for cancer risk assessment. This study aims to investigate the feasibility of DNA methylation-based marker for HNSCC prognosis. Methods: We examined promoter hypermethylation of p16, glutathione S-transferase pi (GSTP1), O6-methylguanine-DNA methyltransferase (MGMT), death-associated protein kinase 1 (DAPK1), RAS-association domain family 1, isoform A (RASSF1A), and E-cadherin (CDH1) genes of 33 HNSCCs paired with adjacent non-tumorous tissues using qualitative methylation-specific PCR (Q-MSP). Of p16 allele, 52 tumors of HNSCC were assayed. Results: Hypermethylation of test promoters was irrelative to gender, stage, recurrence, and differentiation. However, hypermethylation of p16 promoter in tumors was significantly correlated with metastatic lymph node (p=0.003), distant metastasis (p=0.001), or younger patients (p=0.027). Patients with hypermethylated p16 allele have higher risk for distant metastasis than those without (OR=15.3). Of overall survival status, histopathological differentiation grade, recurrence, or distant metastasis was linked to poor diagnosis (p < 0.001, Log rank test). Hypermethylation of p16INK4a promoter was significantly associated with increased distant metastasis (p=0.001) and shortened disease-free time in HNSCC patients older than 52 (p=0.034). Conclusions: This study shows that p16 hypermethylation correlates with increased invasiveness of HNSCC and decreased survival in an age-dependent manner. Our findings not only suggest the potential prognostic value of p16 hypermethylation but also indicate the involvement of p16 with cell migration in HNSCC carcinogenesis.