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Development of microRNA-based liquid biopsy biomarkers and anticancer treatments in digestive system cancers

Research Project

Project/Area Number 18K08690
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 InstitutionKyoto Prefectural University of Medicine

Principal Investigator

Komatsu Shuhei  京都府立医科大学, 医学(系)研究科(研究院), 特任講師 (40578978)

Co-Investigator(Kenkyū-buntansha) 大辻 英吾  京都府立医科大学, 医学(系)研究科(研究院), 教授 (20244600)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsmicroRNA / リキッドバイオプシー / バイオマーカー / エキソソーム / 遊離核酸 / 核酸治療 / 抗がん剤感受性
Outline of Final Research Achievements

Six candidates (miR-126, 133b, 143, 203, 338-3p, 655) of tumour suppressor miRNAs in ESCC were selected by a systematic review of NCBI database. Of these, miR-655 levels were significantly down-regulated in plasma of ESCC patients compared to healthy volunteers by test- and validation-scale analyses. Low levels of plasma miR-655 were significantly associated with lymphatic invasion, lymph node metastasis and advanced stage. Low level of plasma miR-655 was an independent risk factor of lymphatic progression and a poor prognostic factor. Overexpression of miR-655 in ESCC cells inhibited cell proliferation, migration, invasion and epithelial-mesenchymal transition. Increased plasma miR-655 levels by the subcutaneous injection significantly inhibited lymph node metastasis in mice. Low levels of miR-655 in plasma relate to lymphatic progression and poor outcomes, and the restoration of the plasma miR-655 levels might inhibit tumour and lymphatic progression in ESCC.

Academic Significance and Societal Importance of the Research Achievements

遺伝子発現調節に関わるmicroRNAが体液中で安定していることに注目し、血中microRNAを指標とした消化器癌の次世代型バイオマーカー探索を行ってきた。今回、食道癌患者血中で枯渇している癌抑制型miR-655に注目し、予後、リンパ節転移予測の新規バイオマーカーとして有用であり、マウス皮下投与により血中miR-655の濃度回復で、腫瘍増殖・リンパ節転移抑制の抗癌核酸治療の可能性を明らかにした。

Report

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

    (11 results)

All 2021 2020 2019

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 4 results) Presentation (5 results)

  • [Journal Article] TRIM37 contributes to malignant outcomes and CDDP resistance in gastric cancer.2021

    • Author(s)
      Nishibeppu K, Komatsu S, Kiuchi J, Kishimoto T, Takashima Y, Shoda K, Arita T, Kosuga T, Konishi H, Shiozaki A, Kubota T, Okamoto K, Fujiwara H, Tsuda H, Otsuji E.
    • Journal Title

      Journal of Cancer

      Volume: 12 Issue: 2 Pages: 316-325

    • DOI

      10.7150/jca.47577

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Plasma microRNA profiles: identification of miR-1229-3p as a novel chemoresistant and prognostic biomarker in gastric cancer2020

    • Author(s)
      Nishibeppu K, Komatsu S et al.
    • Journal Title

      Sci Rep

      Volume: 10 Issue: 1 Pages: 3161-3161

    • DOI

      10.1038/s41598-020-59939-8

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Circulating circERBB2 as a potential prognostic biomarker for gastric cancer: An investigative study.2020

    • Author(s)
      Nanishi K, Konishi H, Shoda K, Arita T, Kosuga T, Komatsu S, Shiozaki A, Kubota T, Fujiwara H, Okamoto K, Ichikawa D, Otsuji E.
    • Journal Title

      Cancer Science

      Volume: 111 Issue: 11 Pages: 4177-4186

    • DOI

      10.1111/cas.14645

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Involvement of Intracellular and Extracellular High-Mobility Group Box-1 in the Progression of Esophageal Squamous Cell Carcinoma.2020

    • Author(s)
      Matsubara D, Konishi H, Arita T, Shoda K, Fujita Y, Ogino S, Takao K, Nanishi K, Kosuga T, Komatsu S, Shiozaki A, Fujiwara H, Okamoto K, Otsuji E.
    • Journal Title

      Ann Surg Oncol.

      Volume: ー Issue: 9 Pages: 3233-3244

    • DOI

      10.1245/s10434-020-08363-3

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ANO9 Regulated Cell Cycle in Human Esophageal Squamous Cell Carcinoma.2020

    • Author(s)
      Katsurahara K, Shiozaki A, Kosuga T, Kudou M, Shoda K, Arita T, Konishi H, Komatsu S, Kubota T, Fujiwara H, Okamoto K, Kishimoto M, Konishi E, Marunaka Y, Otsuji E.
    • Journal Title

      Ann Surg Oncol.

      Volume: ー Issue: 9 Pages: 3218-3230

    • DOI

      10.1245/s10434-020-08368-y

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Low levels of tumour suppressor miR-655 in plasma contribute to lymphatic progression and poor outcomes in oesophageal squamous cell carcinoma.2019

    • Author(s)
      Kiuchi J, Komatsu S et al.
    • Journal Title

      Molecular cancer

      Volume: 18 Issue: 1 Pages: 2-2

    • DOI

      10.1186/s12943-018-0929-3

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 血中分泌型microRNAを用いた胃癌の抗がん剤感受性診断予測と抗がん核酸治療(英語)2020

    • Author(s)
      小松 周平
    • Organizer
      日本癌学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 分化・未分化混在型胃癌におけるmicroRNAを介した悪性化機序の解明(英語)2020

    • Author(s)
      高嶋 祐助, 小松 周平
    • Organizer
      日本癌学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 消化器癌における筋由来血中miR-133bを用いたサルコペニア病態診断とその治療応用(英語)2020

    • Author(s)
      木内 純, 小松 周平
    • Organizer
      日本癌学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 食道胃接合部腺癌における新規癌関連遺伝子CDCA3の癌化機構の解明と臨床応用(英語)2020

    • Author(s)
      神谷 肇, 小松 周平
    • Organizer
      日本癌学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 胃食道接合部癌における新規の癌関連遺伝子SMYD2の発現意義と臨床応用(英語)2020

    • Author(s)
      大橋 拓馬, 小松 周平
    • Organizer
      日本癌学会総会
    • Related Report
      2020 Annual Research Report

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

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