The management for external auditory canal squamous cell carcinoma based on genomic and proteomic analysis

• Project/Area Number: 17K16883
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Otorhinolaryngology
• Research Institution: Hokkaido University
• Principal Investigator: MORITA SHINYA 北海道大学, 大学病院, 助教 (80443951)
• Project Period (FY): 2017-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 外耳道癌 / 扁平上皮癌 / 遺伝子解析 / 次世代シーケンサー / 予後 / 耳鼻咽喉科学 / 頭頸部癌 / 耳科学 / EGFR / Notch

Outline of Final Research Achievements

This study analyzed genetic mutations based on targeted next-generation sequencing in tissue samples to explore somatic gene mutations associated with the clinicopathological features in patients with external auditory canal squamous cell carcinoma. Gene alterations were most frequently observed in TP53 (59.1%), followed by CREBBP (9.1%). However, except for TP53, this analysis did not identify mutations in major cancer-related gene, such as NOTCH1, FAT1, CDKN2A and PIK3CA. TP53 mutations showed significant correlation with T classification (p=0.027). Multivariable analysis using the Cox proportional hazards model demonstrated that TP53 mutations were independent predictors of overall survival rates for EACSCC patients (p=0.007).

Academic Significance and Societal Importance of the Research Achievements

近年の次世代シーケンサーを用いた遺伝子解析の進歩は著しく、発癌や癌の増殖・生存を制御する癌遺伝子および発現分子を同定し、それらに対する分子標的薬の開発が行われている。本研究から、TP53変異が、外耳道扁平上皮癌の進展度および生存率を予測するためのバイオマーカーとなりえることが示唆された。また、皮膚癌の約30％程度で同定されるCREBBP変異が同定されたことより、外耳道扁平上皮癌の遺伝子変異は皮膚癌に類似している可能性も示唆された。外耳道扁平上皮癌における遺伝子変異および発現分子の解析を報告した研究は少ないため、基礎的な研究に基づいた治療戦略の構築に向けて意義深いものと考えられる。

Research Products

• [Journal Article] Comparison of the University of Pittsburgh staging system and the eighth edition of the American Joint Committee on Cancer TNM classification for the prognostic evaluation of external auditory canal cancer. (2018)
  • Author(s): Morita S, Mizumachi T, Nakamaru Y, Sakashita T, Kano S, Hoshino K, Fukuda A, Fujiwara K, Homma A.
  • Journal Title: Int J Clin Oncol. Volume: 23 Issue: 6 Pages: 1029-1037
  • DOI: 10.1007/s10147-018-1314-3
  • NAID: 120006650534
  • Peer Reviewed
• [Presentation] Comparison of the Pittsburgh staging system and the American Joint Committee on Cancer TNM classification for the prognostic evaluation of external auditory canal cancer (2019)
  • Author(s): Shinya Morita
  • Organizer: 5th Congress of European ORL-HNS
  • Int'l Joint Research
• [Presentation] Prognostic Evaluation of External Auditory Canal Cancer Using Two Different Staging Systems (2019)
  • Author(s): Shinya Morita
  • Organizer: 18th ASEAN ORL-HNS CONGRESS
  • Int'l Joint Research
• [Presentation] 外耳道癌組織における免疫組織化学的手法に基づく発現分子解析 (2017)
  • Author(s): ○森田 真也、本間 明宏、中丸 裕爾、安川 真一郎、福田 篤、福田 諭
  • Organizer: 第118回 日本耳鼻咽喉科学会通常総会・学術講演会
• [Presentation] Immunohistochemistry expression of p53, p16, cyclin D1, EGFR and Notch1 in patients with the temporal bone squamous cell carcinoma (2017)
  • Author(s): Morita S, Nakamaru Y, Fukuda A, Homma A
  • Organizer: 4th Congress of European ORL-HNS
  • Int'l Joint Research