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Clarification of Cdh1 mediated inflammatory carcinogenesis mechanism revealed by spatial gene expression analysis and development of novel preventive strategies.

Research Project

Project/Area Number 21K08009
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53010:Gastroenterology-related
Research InstitutionKumamoto University

Principal Investigator

Naoe Hideaki  熊本大学, 大学院生命科学研究部(医), 准教授 (30599246)

Co-Investigator(Kenkyū-buntansha) 古田 陽輝  熊本大学, 病院, 特任助教 (00869513)
渡邊 丈久  熊本大学, 大学院生命科学研究部(医), 助教 (20634843)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2022: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Keywords炎症性発癌 / 肝腫瘍 / AOM-DSS / 背景大腸粘膜 / Wnt経路 / コリン欠乏高脂肪食 / 肝発癌 / 空間的遺伝子発現解析
Outline of Research at the Start

申請者らはこれまでの研究活動から、Cdh1活性型遺伝子変異マウスがコントロールマウスよりも、多くの大腸腫瘍を形成するという結果を得ている。本研究では、このマウスの肝発癌実験とヒトサンプルを含めて、遺伝子発現や免疫組織学的解析に加え、Visiumを用いた空間的遺伝子発現解析を行うことで、慢性炎症を背景として発生する消化器癌の発癌機構を微小環境の変化も含めて明らかにする。さらに、その結果に基づき、Cdh1や関連する分子を標的とした発癌予防戦略の構築を目指す。

Outline of Final Research Achievements

①Choline-deficient - high-fat diet was fed to control and Cdh1-active mice to induce hepatocellular carcinooma; the number and size of tumours formed in the liver of these mice were measured at 24 and 56 weeks. The results showed no significant differences between the two groups of mice.
②Tumours were formed in the colon of control and Cdh1-active mice induced by the AOM-DSS model. RNA was extracted from these tumours and RNA seq analysis showed no significant deferences between two groups. Therefore, RNA extracted from the backgound inflammatory mucosa surrounding the tumors was analysed and found to be significantly altered in the expression of Wnt6, Wnt10a, Axin, LEF and others between the two groups.

Academic Significance and Societal Importance of the Research Achievements

Cdh1活性型マウスの大腸炎症粘膜において有意に発現が亢進していたRNAはWnt6、Wnt10a、Axin、LEF等であった。これらは、代表的な発癌経路である古典的Wnt-βカテニン経路を構成する遺伝子群である。Cdh1が、Wnt-βカテニン経路と強く関連していたことから、Cdh1が大腸の炎症性発癌の過程で未知の機能を有しているのではないかと考えられる。Cdh1をターゲットにすることで、大腸炎症性発癌の予防あるいは治療法へとつながる可能性が示唆される。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (4 results)

All 2023 2021

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (1 results)

  • [Journal Article] MEFV mutation is possibly associated with intestinal phenotype of Bechet disease2023

    • Author(s)
      FurutaY, Gushima R, Naoe H, Fujimoto N, Honda M, Hirata S, Miyagawa E, Sakatan K, Mizuhashi Y, Iwakura M, Murai Y, Matsuoka M, Komohara Y, Tanaka Y
    • Journal Title

      Journal of Clinical Medicine

      Volume: 12 Issue: 9 Pages: 3131-3131

    • DOI

      10.3390/jcm12093131

    • Related Report
      2023 Annual Research Report 2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Clinical usefulness of inside stents in anastomotic biliary strictures after liver transplantation2023

    • Author(s)
      Kugiyama Naotaka、Hashigo Shunpei、Nagaoka Katsuya、Watanabe Takehisa、Ushijima Shinya、Uramoto Yukiko、Yoshinari Motohiro、Morinaga Jun、Gushima Ryosuke、Tateyama Masakuni、Tanaka Motohiko、Naoe Hideaki、Sugawara Yasuhiko、Hibi Taizo、Tanaka Yasuhito
    • Journal Title

      DEN Open

      Volume: 4 Issue: 1

    • DOI

      10.1002/deo2.305

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical impact of gastrointestinal endoscopy on the early detection of pharyngeal squamous cell carcinoma: A retrospective cohort study.2021

    • Author(s)
      Miyamoto H, Naoe H, Morinaga J, Sakisaka K, Tayama S, Matsuno K, Gushima R, Tateyama M, Shono T, Imuta M, Miyamaru S, Murakami D, Orita Y and Tanaka Y.
    • Journal Title

      World J Gastrointestinal Endoscopy

      Volume: 13 Issue: 10 Pages: 491-501

    • DOI

      10.4253/wjge.v13.i10.491

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 腸管型ベーチェット病/単純性潰瘍におけるMEFV遺伝子変異の検討2021

    • Author(s)
      古田陽輝、直江秀昭、田中靖人
    • Organizer
      第107回日本消化器病学会
    • Related Report
      2021 Research-status Report

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Published: 2021-04-28   Modified: 2025-01-30  

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