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Epigenetic Mechanism Underlying Mucins in Gastric cancer

Research Project

Project/Area Number 15K08955
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Gastroenterology
Research InstitutionNagoya City University

Principal Investigator

Hayashi Kazuki  名古屋市立大学, 大学院医学研究科, 講師 (00405200)

Co-Investigator(Kenkyū-buntansha) 溝下 勤  名古屋市立大学, 大学院医学研究科, 講師 (40347414)
岡本 泰幸  名古屋市立大学, 大学院医学研究科, 助教 (60444973)
Project Period (FY) 2015-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords胃がん / エピジェネティクス / 胃癌
Outline of Final Research Achievements

We analyzed mRNA profile and DNA methylation status, gene mutations of Gastric cancer. We divided into 4 groups from mucin phenotype based on expression status of MUC2、CDX2、VIL1、ALPI. In Null type gastric cancer, which do not express any phenotypic markers, aberrant DNA methylation were enriched, suggesting that these are CpG island methylator phenotype (CIMP). Mutation rate of Null Type gastric cancer is higher than that of the other type gastric cancer because of silencing of mismatch repair gene induced by DNA methylation. PIK3CA mutation were enriched in Null type gastric cancer. It means EB virus associated gastric cancer were involved in Null type gastric cancer. Expression of CD274 and PDCD1, which known as target of immune chechpoint inhibitor, were higher than that of the other group. These data suggest that immune chechpoint inhibitor might be effective in Null type gastric cancer.

Academic Significance and Societal Importance of the Research Achievements

胃癌の粘液性質の分類で、形質発現を認めないNull型関して、その分子生物学的な特徴は十分に報告されていない。また、Null型は予後が悪いことでも知られており、適切な薬物療法の開発が望まれている。本研究でNull型胃癌はDNAメチル化を多く有し、悪性化にDNAメチル化が関連していることがわかった。また、EBウイルス胃癌もNull型に多く含まれることや、CD274とPDCD1の発現が高値であることからも免疫チェックポイント阻害剤が有効である可能性が示唆された。

Report

(5 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (7 results)

All 2018 2016 2015

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (2 results) (of which Invited: 1 results)

  • [Journal Article] The utility and efficacy of self-expandable metal stents for treating malignant gastric outlet obstructions in patients under best supportive care.2018

    • Author(s)
      Hori Y, Naitoh I, Hayashi K, Miyabe K, Yoshida M, Fujita Y, Natsume M, Jinno N, Kato A, Nakazawa T, Shimizu S, Hirano A, Okumura F, Ando T, Sano H, Takada H, Togawa S, Joh T.
    • Journal Title

      Support Care Cancer

      Volume: 26 Issue: 10 Pages: 3587-3592

    • DOI

      10.1007/s00520-018-4221-2

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Case of pancreatic metastasis from colon cancer in which cell block using the Trefle® endoscopic scraper enables differential diagnosis from pancreatic cancer.2018

    • Author(s)
      Kato A, Naitoh I, Kato H, Hayashi K, Miyabe K, Yoshida M, Hori Y, Natsume M, Jinno N, Yanagita T, Takiguchi S, Takahashi S, Joh T.
    • Journal Title

      World J Gastrointest Oncol.

      Volume: 10 Issue: 3 Pages: 91-95

    • DOI

      10.4251/wjgo.v10.i3.91

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Targeting CDK9 Reactivates Epigenetically Silenced Genes in Cancer.2018

    • Author(s)
      Zhang H, Okamoto Y, ISSA JJ
    • Journal Title

      cell

      Volume: 175 Issue: 5 Pages: 1244-1258

    • DOI

      10.1016/j.cell.2018.09.051

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] New concept of traction force applied to biliary self-expandable metallic stents.2016

    • Author(s)
      Hori Y, Hayashi K, Yoshida M, Naitoh I, Nakazawa T, Miyabe K, Shimizu S, Kondo H, Nishi Y, Umemura S, Kato A, Ohara H, Joh T.
    • Journal Title

      Endoscopy

      Volume: 48 Issue: 05 Pages: 472-476

    • DOI

      10.1055/s-0041-111566

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Safety and benefits of self-expandable metallic stents with chemotherapy for malignant gastric outlet obstruction.2015

    • Author(s)
      Miyabe K, Hayashi K, Nakazawa T, Sano H, Yamada T, Takada H, Naitoh I, Shimizu S, Kondo H, Nishi Y, Yoshida M, Umemura S, Hori Y, Kato A, Ohara H, Joh T.
    • Journal Title

      Digestive Endoscopy

      Volume: 27 Issue: 1 Pages: 572-81

    • DOI

      10.1159/000440741

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Current status of Stenting in mGOO 悪性胃・十二指腸狭窄に対するステント留置の現況2018

    • Author(s)
      林 香月
    • Organizer
      第95回日本消化器内視鏡学会学会総会学術集会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] siRNAスクリーニングを用いた、エピゲノム治療標的の探索2018

    • Author(s)
      岡本 泰幸
    • Organizer
      第14回日本消化管学会総会学術集会
    • Related Report
      2017 Research-status Report

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Published: 2015-04-16   Modified: 2020-03-30  

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