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Peritoneal metastasis Prediction by exosome in washing ascites for gastric cancer

Research Project

Project/Area Number 18K16321
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

Harada Kazuto  熊本大学, 病院, 特任助教 (70608869)

Project Period (FY) 2018-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords胃癌 / 腹膜播種 / ゲノム解析 / 次世代シークエンス / Exsosome / 腫瘍免疫 / 腫瘍微小環境 / 腹膜播種再発 / Exosome / 癌関連繊維芽細胞 / バイオマーカー / リキッドバイオプシー / 悪性腹水
Outline of Final Research Achievements

We identified distinct alterations in peritoneal carcinomatosis versus primary lesion in patients with gastric adenocarcinoma (GAC). Alterations associated with aggressive peritoneal carcinomatosis phenotypes emerged with increased mutations in TP53, CDH1, TAF1 and KMT2C, higher level of ’clock-like’ mutational signature, increase in whole-genome doublings, chromosomal instability (particularly, copy number losses), reprogrammed microenvironment, enriched cell cycle pathways, MYC activation and impaired immune response. Integrated analysis identified two main molecular subtypes: ’mesenchymal-like’ and ’epithelial-like’ with discriminating response to chemotherapy (31% vs 71%).

Academic Significance and Societal Importance of the Research Achievements

胃癌の腹膜播種は最も多くみられる転移、再発形式であり、その予後は極めて不良である。腹膜播種の分子生物学的発生メカニズムを解明し、早期診断のバイオマーカーや新規治療戦略を同定することで胃癌の予後を向上させると思われる。我々は胃癌腹膜播種症例の腹水細胞のゲノム解析を行い、腹膜に転移した悪性細胞に特徴的な遺伝子変異を同定した。さらに、免疫抑制に関与するTIM-3の発現が腹水腫瘍細胞の免疫逃避に関与している可能性が明らかにされた、あらたな免疫治療の創薬が期待される

Report

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

    (4 results)

All 2019 Other

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

  • [Int'l Joint Research] MD Anderson Cancer Center(米国)

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Multiplex profiling of peritoneal metastases from gastric adenocarcinoma identified novel targets and molecular subtypes that predict treatment response2019

    • Author(s)
      Wang R, Song S, Harada K(Equally first author), et al.
    • Journal Title

      Gut

      Volume: 69 Issue: 1 Pages: 18-31

    • DOI

      10.1136/gutjnl-2018-318070

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Extracellular vesicles from cancer associated fibroblasts induce drug resistance via integrinβ1/FAK signaling in gastric cancer cells.2019

    • Author(s)
      Uchihara T, Ishimoto T, Miyake K, Yonemura A, Yasuda T, Itoyama R, Iwatsuki M, Baba Y, Yoshida N, Baba H
    • Organizer
      AACR annual meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Identification of aberrant proteins involved in peritoneal dissemination of pancreatic cancer.2019

    • Author(s)
      北村文優、石本崇胤、秋山貴彦、上村紀雄、安田忠仁、米村敦子、伊東山瑠美、内原智幸、東孝暁、今井克憲、林洋光、山下洋市、馬場秀夫
    • Organizer
      The 78th Annual Meeting of the Japanese Cancer Association
    • Related Report
      2019 Annual Research Report

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Published: 2018-04-23   Modified: 2021-02-19  

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