Individualized therapy for primary lung cancer: BIM polymorphism as a stratification factor

• Project/Area Number: 15K09195
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Toho University
• Principal Investigator: ISOBE Kazutoshi 東邦大学, 医学部, 講師 (70385607)
• Co-Investigator(Renkei-kenkyūsha): KABURAKI kyouhei 東邦大学, 医学部, 助教 (00439944)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: BIM遺伝子多型 / PD-L1 / BIMγ / 原発性肺癌 / EGFR遺伝子変異 / BIM-γ / EGFRチロシンキナーゼ阻害薬 / 非小細胞癌 / 非小細胞肺癌

Outline of Final Research Achievements

Expression of BIM protein in primary lung tumors in EGFR-mutated lung adenocarcinoma did not correlate with presence of BIM polymorphism, which was noted in about half of patients. In all patients with BIM polymorphism, BIMγ was expressed in the tumor area or non-tumor area. Moreover, the frequency was significantly higher, and the relative quantification value was nonsignificantly higher, than in patients without BIM polymorphism. Progression-free survival for gefitinib was significantly shorter in patients with positive BIMγ expression, which suggests that BIMγ expression is associated with poor prognosis in patients with EGFR-mutated lung adenocarcinoma receiving gefitinib. In addition, BIM expression in the tumor area significantly positively correlated with PD-L1 expression.

Research Products

• [Journal Article] PD-L1 mRNA expression in EGFR-mutant lung adenocarcinoma (2018)
  • Author(s): Kazutoshi Isobe, Atsushi Kakimoto, Tetuo Mikami, Kyohei Kaburaki, Hiroshi Kobayashi, Takahiro Yoshizawa , Yuta Nakano, Takashi Makino3, Hajime Otsuka, Go Sano, Keishi Sugino, Susumu Sakamoto, Yujiro Takai, Naobumi Tochigi, Akira Iyoda, Sakae Homma
  • Journal Title: Oncology Report Volume: 印刷中
  • Peer Reviewed / Open Access
• [Journal Article] A systematic review and meta-analysis of individual patient data on the impact of the BIM deletion polymorphism on treatment outcomes in epidermal growth factor receptor mutant lung cancer. (2017)
  • Author(s): Soh SX, Siddiqui FJ, Allen JC, Kim GW, Lee JC, Yatabe Y, Soda M, Mano H, Soo RA, Chin TM, Ebi H, Yano S, Matsuo K, Niu X, Lu S, Isobe K, Lee JH, Yang JC, Zhao M, Zhou C, Lee JK, Lee SH, Lee JY, Ahn MJ, Tan TJ, Tan DS, Tan EH, Ong ST, Lim WT.
  • Journal Title: Oncotarget Volume: 印刷中 Issue: 25 Pages: 41474-41486
  • DOI: 10.18632/oncotarget.17102
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Association of BIM Deletion Polymorphism and BIM-γ RNA Expression in NSCLC with EGFR Mutation. (2016)
  • Author(s): Isobe K, Kakimoto A, Mikami T, Kaburaki K, Kobayashi H, Yoshizawa T, Makino T, Otsuka H, Sano GO, Sugino K, Sakamoto S, Takai Y, Tochigi N, Iyoda A, Homma S.
  • Journal Title: Cancer Genomics Proteomics. Volume: 13 Pages: 475-482
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 特発性肺線維症におけるBCL2L11遺伝子多型とレドックスの検討 (2018)
  • Author(s): 磯部和順、一色琢磨，鏑木教平，小林 紘，卜部尚久，伊藤貴文，澤田哲郎，佐野 剛，坂本 晋，高井雄二郎，伊豫田 明，澁谷和俊，本間 栄
  • Organizer: 第58回日本呼吸器学会
• [Presentation] EGFR遺伝子変異陽性肺腺癌術後再発例におけるPD-L1のmRNA発現の検討 (2016)
  • Author(s): 磯部和順、鏑木教平、小林紘、吉澤孝浩、 牧野 崇、大塚 創、柿本篤志、栃木直文、 三上哲夫、伊豫田 明、本間 栄
  • Organizer: 第57回日本肺癌学会学術集会
  • Place of Presentation: 福岡国際会議場(福岡県福岡市）
  • Year and Date: 2016-12-19
• [Presentation] EGFR遺伝子変異陽性肺腺癌におけるPD-L1のmRNA発現の検討 (2016)
  • Author(s): 磯部和順、鏑木教平、小林紘、吉澤孝浩、 牧野 崇、大塚 創、柿本篤志、栃木直文、 三上哲夫、伊豫田 明、本間 栄
  • Organizer: 第14回日本臨床腫瘍学会学術集会
  • Place of Presentation: 神戸国際展示場(兵庫県神戸市）
  • Year and Date: 2016-07-28
• [Presentation] EGFR遺伝子変異陽性肺腺癌におけるBIM-isoform発現の検討 (2016)
  • Author(s): 磯部和順、鏑木教平、吉澤孝浩、小林紘、柿本篤志、高井雄二郎、栃木直文、伊豫田明、三上哲夫、本間栄
  • Organizer: 第56回日本呼吸器学会学術集会
  • Place of Presentation: 国立京都国際会館（京都府京都市）
  • Year and Date: 2016-04-10
• [Presentation] EGFR遺伝子変異陽性肺腺癌におけるBIM遺伝子多型と原発巣のBIM蛋白発現の関連性の検討 (2015)
  • Author(s): 磯部和順、秦美暢、栃木直文、鏑木教平、吉澤孝浩、小林紘、佐野剛、杉野圭史、坂本晋、高井雄二郎、柿本篤志、伊豫田明、三上哲夫、本間栄
  • Organizer: 第56回日本肺癌学会学術集会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2015-11-28