Exploration of novel biomarkers in KRAS mutant-lung cancer using comprehensive gene expression analysis

• Project/Area Number: 17K16613
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Respiratory surgery
• Research Institution: Fukushima Medical University
• Principal Investigator: Yamaura Takumi 福島県立医科大学, 医学部, 博士研究員 (20747240)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2017: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 肺癌 / KRAS / FAM83B / EGFR / 肺腺癌 / PD-L1 / バイオマーカー

Outline of Final Research Achievements

We focused on Family with sequence similarity 83, member B (FAM83B). In eight cases of KRAS mutant-lung adenocarcinoma (ADC), FAM83B was highly expressed in mucinous ADC tissue. Next, we compared FAM83B expression in lung ADC stratified by presence or absence of EGFR mutation, which is widely examined clinically and has an exclusive relation with KRAS mutation. FAM83B was significantly highly expressed in EGFR wild type group, that contain with a relatively high proportion of KRAS mutant-ADC. High FAM83B group had shorter postoperative recurrence-free survival and overall survival regardless of presence or absence of EGFR gene mutation significantly. Growth inhibition was confirmed by FAM83B RNAi in lung cancer-derived cell lines.

Academic Significance and Societal Importance of the Research Achievements

本研究でFAM83Bが肺腺癌増殖と関連する因子であることが示された。肺腺癌の内KRAS遺伝子変異は粘液産生性肺腺癌との関連があり、この両者はそれぞれに治療抵抗性を示し予後不良な症例群であると報告されている。上記症例群でFAM83Bが高発現である、またFAM83Bを治療標的とした増殖阻害が臨床治療に応用できる可能性があると考えられ今後の検討を要する。肺癌診療への貢献が期待される。

Research Products

• [Journal Article] Pseudoprogression and Rapid Response to Pembrolizumab in a Patient with Advanced Lung Adenocarcinoma with Loss of Epidermal Growth Factor Receptor Gene Mutation after Tyrosine Kinase Inhibitor Therapy (2018)
  • Author(s): Yamaura Takumi、Suzuki Hiroyuki
  • Journal Title: Journal of Thoracic Oncology Volume: 13 Issue: 10 Pages: e209-e210
  • DOI: 10.1016/j.jtho.2018.05.021
  • Peer Reviewed
• [Journal Article] Prognostic Impact of Tumor Mutation Burden in Patients With Completely Resected Non-Small Cell Lung Cancer: Brief Report (2018)
  • Author(s): Owada-Ozaki Yuki、Muto Satoshi、Takagi Hironori、Inoue Takuya、Watanabe Yuzuru、Fukuhara Mitsuro、Yamaura Takumi、Okabe Naoyuki、Matsumura Yuki、Hasegawa Takeo、Ohsugi Jun、Hoshino Mika、Shio Yutaka、Nanamiya Hideaki、Imai Jun-ichi、Isogai Takao、Watanabe Shinya、Suzuki Hiroyuki
  • Journal Title: Journal of Thoracic Oncology Volume: 13 Issue: 8 Pages: 1217-1221
  • DOI: 10.1016/j.jtho.2018.04.003
  • Peer Reviewed
• [Journal Article] Family with sequence similarity 83, member B is a predictor of poor prognosis and a potential therapeutic target for lung adenocarcinoma expressing wild-type epidermal growth factor receptor. (2018)
  • Author(s): Yamaura T, Ezaki J, Okabe N, Takagi H, Ozaki Y, Inoue T, Watanabe Y, Fukuhara M, Muto S, Matsumura Y, Hasegawa T, Hoshino M, Osugi J, Shio Y, Waguri S, Tamura H, Imai JI, Ito E, Yanagisawa Y, Honma R, Watanabe S, Suzuki H.
  • Journal Title: Oncology Letters Volume: 15 Pages: 1549-1558
  • DOI: 10.3892/ol.2017.7517
  • Peer Reviewed / Open Access
• [Presentation] 肺腺癌切除検体におけるPD-L1発現の検討 (2018)
  • Author(s): 山浦 匠, 尾崎有紀, 福原光朗, 武藤哲史, 岡部直行, 長谷川剛生, 塩 豊, 鈴木弘行
  • Organizer: 第35回日本呼吸器外科学会総会・学術集会
• [Presentation] 肺腺癌におけるPD-L1発現の検討 (2018)
  • Author(s): 山浦 匠, 髙木玄教, 尾崎有紀, 武藤哲史, 岡部直行, 長谷川剛生, 塩 豊, 鈴木弘行
  • Organizer: 第59回日本肺癌学会学術集会
• [Presentation] EGFR-TKIによりEGFR遺伝子変異が消失しPD-1阻害療法でPseudo-progressionを伴う急激な奏功を認めた一例 (2018)
  • Author(s): 山浦 匠, 尾崎有紀, 井上卓哉, 福原光朗, 武藤哲史, 岡部直行, 長谷川剛生, 塩 豊, 鈴木弘行
  • Organizer: 第31回日本バイオセラピィ学会学術集会総会
• [Presentation] Functional analysis of Family with sequence similarity 83, member B in lung adenocarcinoma from Translational Research in Fukushima Medical University (2017)
  • Author(s): Takumi Yamaura，Naoyuki Okabe，Yuki Owada, Takuya Inoue, Mitsuro Fukuhara, Satoshi Muto, Takeo Hasegawa, Junji, Ezaki, Takao Isogai, Shinya Watanabe, Hiroyuki Suzuki
  • Organizer: 第117回日本外科学会定期学術集会
• [Presentation] Clinical and therapeutic impact of family with sequence similarity 83, member B in EGFR gene wild type-lung adenocarcinoma (2017)
  • Author(s): Yamaura T, Ezaki J, Okabe N, Takagi H, Ozaki Y, Inoue T, Watanabe Y, Fukuhara M, Muto S, Matsumura Y, Hasegawa T, Hoshino M, Osugi J, Shio Y, Waguri S, Tamura H, Imai JI, Ito E, Yanagisawa Y, Honma R, Watanabe S, Suzuki H
  • Organizer: 2017 ASCO Annual meeting
  • Int'l Joint Research