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

The new classification of colorectal cancer focusing on differences of molecular mechanisms in TGF-b signal pathway

Research Project

Project/Area Number 18K08612
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 55020:Digestive surgery-related
Research InstitutionNiigata University

Principal Investigator

Shimada Yoshifumi  新潟大学, 医歯学系, 講師 (20706460)

Co-Investigator(Kenkyū-buntansha) 若井 俊文  新潟大学, 医歯学系, 教授 (50372470)
亀山 仁史  新潟大学, 医歯学総合研究科, 客員研究員 (40626420)
永橋 昌幸  新潟大学, 医歯学総合病院, 研究准教授 (30743918)
市川 寛  新潟大学, 医歯学系, 助教 (50721875)
田島 陽介  藤田医科大学, 医学部, 講師 (30757505)
小林 隆  新潟大学, 医歯学系, 准教授 (40464010)
奥田 修二郎  新潟大学, 医歯学系, 准教授 (00512310)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords大腸癌 / TGF-β / TGFBR2 / ACVR2A / SMAD2 / SMAD4 / TMB-H / 低分化胞巣 / 腫瘍内リンパ球浸潤 / 発癌 / 発癌メカニズム
Outline of Final Research Achievements

We classified colorectal cancer (CRC) with abnormalities in the TGF-β signaling pathway into TGFBR2/ACVR2A mutation group (“Receptor mutation group”) or SMAD2/SMAD4 mutation group (“Regulator mutation group”). We demonstrated that “Receptor mutation group” was associated with tumor mutational burden-high (TMB-H) CRC, which is expected to be effective for immunotherapy, and developed artificial intelligence to predict TMB-H CRC. SMAD4, “Regulator mutation group”, was associated with poorly differentiated clusters, and was associated with poor prognosis in CRC.

Academic Significance and Societal Importance of the Research Achievements

本研究の学術的意義は、TGF-βシグナル伝達経路に異常を有する大腸癌の臨床病理学的特徴を明らかにしたことによって、分子サブタイプによる新たな大腸癌の分類の基盤形成を行ったことである。
本研究の社会的意義は、TMB-H大腸癌を予測する人工知能を開発したことによって、低コストで大腸癌の個別化治療を推進するモデルを提案したことである。また、大腸癌のドライバー遺伝子変異の一つと考えられるSMAD4遺伝子変異の臨床病理学的特徴を明らかにしたことによって、SMAD4遺伝子変異を標的とした新たな治療開発の基盤形成を行ったことである。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (3 results)

All 2021 2020 2019

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results)

  • [Journal Article] Histopathological characteristics and artificial intelligence for predicting tumor mutational burden-high colorectal cancer2021

    • Author(s)
      Shimada Yoshifumi、Okuda Shujiro、Watanabe Yu、Tajima Yosuke、Nagahashi Masayuki、Ichikawa Hiroshi、Nakano Masato、Sakata Jun、Takii Yasumasa、Kawasaki Takashi、Homma Kei-ichi、Kamori Tomohiro、Oki Eiji、Ling Yiwei、Takeuchi Shiho、Wakai Toshifumi
    • Journal Title

      Journal of Gastroenterology

      Volume: - Issue: 6 Pages: 547-559

    • DOI

      10.1007/s00535-021-01789-w

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] RNF43 mutation is associated with aggressive tumor biology along with BRAF V600E mutation in right-sided colorectal cancer2020

    • Author(s)
      Matsumoto A, Shimada Y, Nakano M, Oyanagi H, Tajima Y, Nakano M, Kameyama H, Hirose Y, Ichikawa H, Nagahashi M, Nogami H, Maruyama S, Takii Y, Ling Y, Okuda S, Wakai T.
    • Journal Title

      Oncology Reports

      Volume: 43 Pages: 1853-1862

    • DOI

      10.3892/or.2020.7561

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] SMAD4 alteration associates with invasive-front pathological markers and poor prognosis in colorectal cancer2019

    • Author(s)
      Oyanagi H, Shimada Y, Nagahashi M, Ichikawa H, Tajima Y, Abe K, Nakano M, Kameyama H, Takii Y, Kawasaki T, Homma KI, Ling Y, Okuda S, Takabe K, Wakai T.
    • Journal Title

      Histopathology

      Volume: 74 Issue: 6 Pages: 873-882

    • DOI

      10.1111/his.13805

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access

URL: 

Published: 2018-04-23   Modified: 2022-01-27  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi