Epigenetic Alterations in the Drug Resistance of Oral Squamous Cell Carcinoma

Hirosue, Akiyuki

Epigenetic Alterations in the Drug Resistance of Oral Squamous Cell Carcinoma

Akiyuki Hirosue DDS, PhD, Department of Oral and Maxillofacial Surgery, Kumamoto University, Kumamoto, Japan

Chiho Nakamura , Department of Oral and Maxillofacial Surgery, Kumamoto University, Kumamoto, Japan

Masafumi Nakamoto , Department of Oral and Maxillofacial Surgery, Kumamoto University, Kumamoto, Japan

Kenta Kawahara DDS, PhD, Department of Oral and Maxillofacial Surgery, Kumamoto University, Kumamoto, Japan

Akihiro Muta DDS, Department of Oral and Maxillofacial Surgery, Kumamoto University, Kumamoto, Japan

Masatoshi Hirayama DDS, Department of Oral and Maxillofacial Surgery, Kumamoto University, Kumamoto, Japan

Ryoji Yoshida , Department of Oral and Maxillofacial Surgery, Kumamoto University, Kumamoto, Japan

Masashi Nagata , Department of Oral and Maxillofacial Surgery, Kumamoto University, Kumamoto, Japan

Hideki Nakayama , Department of Oral and Maxillofacial Surgery, Kumamoto University, Kumamoto, Japan

Akimitsu Hiraki , Department of Oral and Maxillofacial Surgery, Kumamoto University, Kumamoto, Japan

Masanori Shinohara , Department of Oral and Maxillofacial Surgery, Kumamoto University, Kumamoto, Japan

Chemotherapeutic resistance is a key obstacle to effective cancer treatment in oral squamous cell carcinoma (OSCC). Epigenetic alterations, particularly DNA methylation have been extensively studied for future diagnosis, prognosis and prediction of response to therapies in a variety of cancers. However, the contribution of epigenetic changes to the development of drug resistance in OSCC remains to be elucidated. Herein, we investigated the relevance between clinical effect and methylation frequency in OSCC samples. DNA was extracted 5-fluorouracil (5-FU) resistant OSCC cell lines and biopsy samples of OSCC patients who underwent surgery after 5-FU based chemoradiotherapy, and methylation frequencies were evaluated by quantitative methylation specific PCR (MSP) assay. We focused on tumor suppressor genes (MGMT, DAPK1) and drug resistant-related genes. MSP assay indicated that hypermethylation of these genes was associated with pathological response to 5-FU based chemoradiotherapy. These results suggest that methylation status of these genes may provide the prediction of drug sensitivity in OSCC.