Analysis of epigenomic alterations in chemoresistance and radioresistance of oral squamous cell carcinoma to provide the personalized medicine.

• Project/Area Number: 26861738
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Surgical dentistry
• Research Institution: Kumamoto University
• Principal Investigator: Hirosue Akiyuki 熊本大学, 医学部附属病院, 助教 (00638182)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 口腔癌 / エピゲノム / DNAメチル化 / ヒストン修飾 / 抗癌剤耐性 / 放射線耐性 / エピジェネティクス治療薬

Outline of Final Research Achievements

Chemo-radiotherapy resistance is a key obstacle to effective cancer treatment in oral squamous cell carcinoma (OSCC). Epigenomic alterations, particularly DNA methylation have been extensively studied for future diagnosis, prognosis and prediction of therapeutic response in a variety of cancers. However, the contribution of epigenetic changes to the development of chemo-radiotherapy resistance in OSCC remains to be elucidated. Herein, we investigated the relevance between clinical effect and epigenomic alterations in OSCC to develop the novel diagnostic methods based on epigenomic profile. DNA methylation frequencies were evaluated by quantitative methylation specific PCR (MSP) assay. MSP assay indicated that hypermethylation of MGMT, TFAP2E and DAPK1 was associated with pathological response to 5-FU based chemo-radiotherapy and overall survival. These results suggest that methylation status of these genes may provide the prediction of chemosensitivity and radiosensitivity in OSCC.

Research Products

• [Journal Article] Pre-treatment neutrophil to lymphocyte ratio predicts the chemoradiotherapy outcome and survival in patients with oral squamous cell carcinoma (2016)
  • Author(s): Hikaru Nakashima, Yuichiro Matsuoka, Ryoji Yoshida, Masashi Nagata, Akiyuki Hirosue, Kenta Kawahara, Jyunki Sakata, Hidetaka Arita, Akimitsu Hiraki and Hideki Nakayama
  • Journal Title: BMC Cancer Volume: 26 Issue: 1 Pages: 41-41
  • DOI: 10.1186/s12885-016-2079-6
  • Peer Reviewed / Open Access
• [Journal Article] The tumour stromal features are associated with resistance to 5-FU-based chemoradiotherapy and a poor prognosis in patients with oral squamous cell carcinoma. (2015)
  • Author(s): Matsuoka Y, Yoshida R, Nakayama H, Nagata M, Hirosue A, Tanaka T, Kawahara K, Nakagawa Y, Sakata J, Arita H, Hiraki A, Shinohara M.
  • Journal Title: APMIS Volume: 3 Issue: 3 Pages: 205-14
  • DOI: 10.1111/apm.12344
  • Peer Reviewed / Open Access
• [Journal Article] Phase II clinical trial of multiple peptide vaccination for advanced head and neck cancer patients revealed induction of immune responses and improved OS (2015)
  • Author(s): Yoshitake, Y., Fukuma, D., Yuno, A., Hirayama, M., Nakayama, H., Tanaka. T., Nagata, M., Takamune, Y., Kawahara, K., Nakagawa, Y., Yoshida, R., Hirosue, A., Ogi, H., Hiraki, A. , Jono, H., Hamada, A., Yoshida, K., Nishimura, Y., Nakamura, Y., Shinohara, M.
  • Journal Title: Clinical Cancer Research Volume: 21 Issue: 2 Pages: 312-321
  • DOI: 10.1158/1078-0432.ccr-14-0202
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A case of adenomatoid odontogenic tumor-like tumor, unusual benign odontogenic tumor in the maxilla. (2015)
  • Author(s): Kawahara K., Nakayama H., Fukuma D., Nagata M., Yoshida R., Tanaka T., Nakagawa Y., Hirosue A., Hiraki A., Takeda Y & Shinohara M.
  • Journal Title: Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology Volume: 27 Issue: 2 Pages: 299-302
  • DOI: 10.1016/j.ajoms.2014.05.001
  • Peer Reviewed
• [Presentation] Epigenetic alterations in chemoresistance and radioresistance of oral squamous cell carcinoma. (2015)
  • Author(s): A. Hirosue, M. Nakamoto, T. Yamamoto, Y. Matsuoka, C. Nakamura, K. Kawahara, R. Yoshida, A. Hiraki, H. Nakayama, M. Shinohara
  • Organizer: 22nd International conference on oral & maxillofacial surgery
  • Place of Presentation: メルボルン、オーストラリア
  • Year and Date: 2015-10-27
  • Int'l Joint Research
• [Presentation] Increased expression of HMGA2 predicts metastasis and poor prognosis in oral squamous cell carcinoma. (2015)
  • Author(s): Junki S，Akiyuki H，Ryoji Y，Masashi N，Yuichiro M，Hidetaka A，Kenta K，Yoshihiro N. Masashi N，Akimitsu H，Masanori S，Hideki N
  • Organizer: 第74回日本癌学会総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2015-10-08
• [Presentation] Epigenetic alterations in the drug resistance of oral squamous cell carcinoma. (2014)
  • Author(s): Akiyuki Hirosue
  • Organizer: 96th Annual Meeting, Scientific Sessions & Exhibition in conjunction with the Japanese Society and Korean Association of Oral and Maxilllofacial Surgeons
  • Place of Presentation: Hawaii Convention Center
  • Year and Date: 2014-09-08 – 2014-09-13