Identification of HPV-associated oropharyngeal carcinoma poor prognostic factor using microRNA and epigenome analysis

• Project/Area Number: 18K16850
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56050:Otorhinolaryngology-related
• Research Institution: Yokohama City University
• Principal Investigator: HATANO Takashi 横浜市立大学, 附属病院, 助教 (40807583)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: ヒト乳頭腫ウイルス関連中咽頭癌 / 頭頸部癌 / エピゲノム / マイクロRNA / HPV / microRNA

Outline of Final Research Achievements

From previous studies, we performed comprehensive microRNA profiling of human papilloma virus (HPV)-associated head and neck squamous cell carcinoma cell lines and microRNAs that are thought to have an impact on prognosis among microRNAs whose expression fluctuates due to HPV infection were extracted.Then, by varying the expression of the extracted mirB, we obtained a significant difference in cell growth and migration in vitro, and further revealed that it regulates the expression of candidate downstream genes extracted from multiple public databases. These results suggest that mirB enhances proliferation and migration in the carcinogenic mechanism of HPV-associated oropharyngeal carcinoma.

Academic Significance and Societal Importance of the Research Achievements

HPV関連中咽頭癌はHPV陰性癌と比較し予後が良好と考えられているが、その中にも予後不良な症例は依然として存在しており、その理由は明らかではない。
本研究で明らかにしたmirBを介した下流遺伝子の制御機構に対する治療開発を行うことで、HPV関連中咽頭癌の予後不良群改善への糸口となる可能性がある。

Research Products

• [Journal Article] The Advances in Research of Human Papillomavirus-Induced Carcinogenesis in Oropharyngeal Cancers (2019)
  • Author(s): Hatano Takashi, Sano Daisuke, Oridate Nobuhiko.
  • Journal Title: Gan To Kagaku Ryoho. Volume: 46(7) Pages: 1128-1130
  • Peer Reviewed
• [Journal Article] Real-world Treatment Outcomes of the EXTREME Regimen as First-line Therapy for Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck: A Multi-center Retrospective Cohort Study in Japan (2019)
  • Author(s): Sano D, Fujisawa T, Tokuhisa M, Shimizu M, Sakagami T, Hatano T, Nishimura G, Ichikawa Y, Iwai H, Oridate N
  • Journal Title: Anticancer Research Volume: 39 Issue: 12 Pages: 6819-6827
  • DOI: 10.21873/anticanres.13898
  • Peer Reviewed / Open Access
• [Journal Article] A prospective clinical trial of the second-look procedure for transoral surgery in patients with T1 and T2 laryngeal, oropharyngeal, and hypopharyngeal cancer. (2019)
  • Author(s): Nishimura Goshi, Sano Daisuke, Arai Yasuhiro, Hatano Takashi, Takahashi Hideaki, Tanabe Teruhiko, Wada Takashi, Morishita Daiki, Oridate Nobuhiko.
  • Journal Title: Cancer Medecine. Volume: 8(17) Issue: 17 Pages: 7197-7206
  • DOI: 10.1002/cam4.2588
  • Peer Reviewed / Open Access
• [Presentation] Establishment of PDX-derived salivary gland adenoid cystic carcinoma cell lines using organoid culture method (2019)
  • Author(s): 高田 顕太郎, 相澤 圭洋, 佐野 大佑, 奥田 諒, 関根 圭輔, 上野 康晴, 青山 準, 波多野 孝, 荒井 康裕, 谷口 英樹, 折舘 伸彦
  • Organizer: 第78回日本癌学会総会
  • Int'l Joint Research
• [Presentation] FOSL1 promotes regional metastasis of head and neck squamous cell carcinoma (2018)
  • Author(s): 佐野 大佑, 澤熊 香衣, 百束 紘, 波多野 孝, 磯野 泰大, 高田 顕太郎, 佐藤 要, 桑原 達, 相澤 圭洋, 折舘 伸彦
  • Organizer: 第77回日本癌学会総会
  • Int'l Joint Research