Development of lung cancer diagnostic method by measuring drebrin and elucidation of molecular function of drebrin in lung carcinoma

Research Project

Project/Area Number	18K15954
Research Category	Grant-in-Aid for Early-Career Scientists
Allocation Type	Multi-year Fund
Review Section	Basic Section 53030:Respiratory medicine-related
Research Institution	Kumamoto University
Principal Investigator	Iyama Shinji 熊本大学, 病院, 特任助教 (70806497)
Project Period (FY)	2018-04-01 – 2022-03-31
Project Status	Completed (Fiscal Year 2021)
Budget Amount *help	¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000) Fiscal Year 2021: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000) Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000) Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000) Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords	ドレブリン / がん微小環境 / 術後再発 / 肺がん / 肺扁平上皮がん / 非小細胞肺がん / 腫瘍免疫 / 肺腺がん / がんマーカー
Outline of Final Research Achievements	Peripheral blood and malignant pleural effusions in drebrin assays were difficult to analyze. We analyzed the function of drebrin in the lung cancer microenvironment.We evaluated 34 surgical specimens of pathological stage I-IIIA lung squamous cell carcinoma. The immune contexture of surgically resected primary tumors was investigated by fluorescent multiplex immunohistochemistry. High-speed scanning of whole slide images was performed on stained tissue sections. Pan-cytokeratin of tumor cells, CD3 and drebrin were simultaneously stained. Tissue localizations of TILs in the tumor cell nest and surrounding tumor stroma were profiled and quantified by an automated quantitative pathology imaging system.A higher density of drebrin-positive CD3+ T-cells in tumor cell nest was significantly associated with a shorter overall survival.This study provides the first evidence of prognostic value of tumor-infiltrating drebrin-positive T-cells in patients with resected lung squamous cell carcinoma.
Academic Significance and Societal Importance of the Research Achievements	進行期・術後再発非小細胞肺がんの治療は抗がん剤を中心とした化学療法が行われる。肺がん患者の死亡数を減らすための対策の一部に①早期非小細胞肺がん手術後再発を予測し、早期に治療介入を行うこと、②進行期非小細胞肺がんに対する治療成績を上げることが考えられる。肺がん手術後の再発を減らすために術後化学療法が実臨床で行われ、再発率が6-15％の向上が得られる。我々の報告により肺扁平上皮がんにおける腫瘍内ドレブリン発現Tリンパ球の割合が高いことが予後不良マーカーであることを示した。術後の検査治療管理にドレブリン発現Tリンパ球が有用である可能性がある。