Integrated regulatory mechanism that govern differentiation and survival of driver-mutation-independent lung adenocarcinoma

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H02634
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Jichi Medical University
• Principal Investigator: niki toshiro 自治医科大学, 医学部, 教授 (90198424)
• Co-Investigator(Kenkyū-buntansha): 萩原 弘一 自治医科大学, 医学部, 教授 (00240705) ; 遠藤 俊輔 自治医科大学, 医学部, 教授 (10245037) ; 佐久間 裕司 札幌医科大学, 医学部, 准教授 (10364514) ; 吉本 多一郎 自治医科大学, 医学部, 非常勤講師 (20634166) ; 松原 大祐 自治医科大学, 医学部, 准教授 (80415554)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 肺腺癌 / 分子標的 / 上皮間葉転換

Outline of Final Research Achievements

Non-TRU (terminal respiratory unit)-type lung adenocarcinoma lacks driver mutations, such as EGFR, and consists of cases that show either 1) abnormal gastrointestinal differentiation, or 2) loss of epidermal traits. In this study, we first clarified the significance of two factors, TFF(trefoil factor family)-1 and HNF(hepatocyte nuclear factor) 4α, as novel biomarkers of the former non-TRU-type, and then examined the effect of their knock-down in lung adenocarcinoma with gastrointestinal differentiation. We also obtained data indicating that loss of BRM, often found in the latter non-TRU-type, is causally related to the loss of epidermal differentiation in this group of non-TRU-type lung adenocarcinoma.

Free Research Field

人体病理

Academic Significance and Societal Importance of the Research Achievements

肺腺癌は，ドライバー変異に基づいた治療が行われているが，治療標的の不明な癌が未だ30％ほど残っている．このような症例は，肺のmaster gene TTF-1が陰性で，上皮形質の異常を示すnon-TRU-type腺癌に多い．本研究は，non-TRU-type腺癌の特徴を分子レベルで明らかにしたもので，今後non-TRU-type腺癌の診断と治療戦略を考えるうえで重要な基盤となる基礎研究である．