• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2020 Fiscal Year Final Research Report

Investigation of the impact of ARID1A mutation on molecular characteristics in colorectal cancer

Research Project

  • PDF
Project/Area Number 19K18155
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 55020:Digestive surgery-related
Research InstitutionKumamoto University

Principal Investigator

TOKUNAGA Ryuma  熊本大学, 病院, 非常勤診療医師 (20594881)

Project Period (FY) 2019-04-01 – 2021-03-31
KeywordsARID1A / 大腸癌 / クロマチンリモデリング因子 / マイクロサテライト不安定性 / 免疫チェックポイント阻害剤
Outline of Final Research Achievements

The impact of ARID1A mutations on molecular characteristics in colorectal cancer was analyzed using a total of 7,978 clinical samples. ARID1A mutations were associated with right-sided tumor and earlier stage in colorectal cancer. In addition, ARID1A mutant samples had more favorable immune-profiles indicative of a higher likelihood of response to immune check point inhibitors; genomically unstable tumor features (MSI-high and TMB-high) and the characteristics of a T-cell-inflamed microenvironment (PD-L1 expression and high estimated-infiltrating cytotoxic T lymphocytes (CTLs)), than ARID1A wild-type samples. Even ARID1A mutant samples without MSI-high status were TMB-high, had high levels of PD-L1 expression, and high estimated-infiltrating CTLs. With co-occurring mutations and regulating pathways, ARID1A mutations might be a predictive biomarker for chemo/radio-therapy and targeted-therapy.

Free Research Field

消化器癌(主に大腸癌)における集学的治療および橋渡し研究

Academic Significance and Societal Importance of the Research Achievements

大腸癌は本邦における癌罹患数および臓器別癌死亡数で上位を占め、世界的に研究がすすめられている癌腫である。ARID1Aはクロマチンリモデリング因子であり、各癌腫において比較的高率にその遺伝子変異を認めると報告されている。我々は大腸癌においてARID1A変異がきたす現象変化を明らかにし、新規治療標的を開発することを目標に研究を行った。今回の研究においてARID1A変異が大腸癌における免疫チェックポイント阻害剤および化学療法/放射線療法の効果予測因子である可能性を初めて示すことができた。これは大腸癌のみならず各種癌に対する治療法確立につながる可能性がある。

URL: 

Published: 2022-01-27  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi