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Development and clinical application of universal prognostic score for gastrointestinal tumors

Research Project

Project/Area Number 19K20403
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 62010:Life, health and medical informatics-related
Research InstitutionKyushu University

Principal Investigator

Hideyuki Shimizu  九州大学, 生体防御医学研究所, 学術研究員 (70826263)

Project Period (FY) 2019-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords個別化医療 / 層別化 / 人工知能 / 消化器がん / 大腸がん / 胃がん / 予後 / 予後予測 / 大規模データ
Outline of Research at the Start

胃がん大腸がんの患者さんの遺伝子発現データと臨床データについて、既存の文献報告を統計学的に統合し、人種を超えて消化器がんにおいて予後に関わる遺伝子群を同定する。それらの中から最適な遺伝子の組み合わせを調べるために、機械学習的なアプローチを採用していく。患者さんの生存率を層別化するような人工知能のモデルを構築し、予後予測器を生成する。人工知能によって予後予測に特に重要だと判断されたいくつかの遺伝子について、胃がんおよび大腸がんの細胞株を使い、分子生物学的な実験にてその意義を明らかにし、そこから有望な治療戦略を考案する。

Outline of Final Research Achievements

Cancer is the leading cause of death among Japanese people, and among them, there are many patients with colorectal and gastric cancer. In the treatment methods that have been used so far, patients have been divided into several groups, and treatment within each group has been generally the same. However, from the perspective of personalized medicine, more precise stratification is desirable. Therefore, we used statistics and machine learning to unravel the relationship between prognosis and gene expression in thousands of patients, and created a score called mPS_colon. The usefulness of this score was validated in a number of patient cohorts, and it outperformed existing stratification methods. We hope that it will be applied to clinical practice in the future.

Academic Significance and Societal Importance of the Research Achievements

これまで大腸がん・胃がんにおいてさまざまな予後規定遺伝子が報告されてきたが、いずれもごく限られた患者データや実験データから得られた報告であった。今回我々は数千人という大規模の患者データを統合し、具体的な予後層別化スコアを提唱したところに大きな学術的な意義がある。また社会的にも、このシステムを使えば本来は化学療法をしなくてもいい患者さんを同定できるため、過剰な治療を避けることにつながる。

Report

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

    (8 results)

All 2021 2020 2019

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 5 results) Presentation (2 results) (of which Invited: 2 results)

  • [Journal Article] A universal molecular prognostic score for gastrointestinal tumors2021

    • Author(s)
      Shimizu Hideyuki、Nakayama Keiichi I.
    • Journal Title

      npj Genomic Medicine

      Volume: 6 Issue: 1 Pages: 6-6

    • DOI

      10.1038/s41525-021-00172-1

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Loss of Fbxw7 impairs development of and induces heterogeneous tumor formation in the mouse mammary gland2020

    • Author(s)
      Onoyama Ichiro、Nakayama Shogo、Shimizu Hideyuki、Nakayama Keiichi I.
    • Journal Title

      Cancer Research

      Volume: 80 Issue: 24 Pages: 5515-5530

    • DOI

      10.1158/0008-5472.can-20-0271

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A shift in glutamine nitrogen metabolism contributes to malignant progression of cancer.2020

    • Author(s)
      Kodama M, Oshikawa K, Shimizu H, Yoshioka S, Takahashi M, Izumi Y, Bamba T, Tateishi C, Tomonaga T, Matsumoto M*, Nakayama KI*.
    • Journal Title

      Nat. Commun.

      Volume: 11 Issue: 1 Pages: 1320-1320

    • DOI

      10.1038/s41467-020-15136-9

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Fail-Safe System to Prevent Oncogenesis by Senescence Is Targeted by SV40 Small T Antigen2020

    • Author(s)
      Kiyotaka Oshikawa, Masaki Matsumoto, Manabu Kodama, Hideyuki Shimizu, Keiichi I Nakayama
    • Journal Title

      Oncogene

      Volume: 39 Issue: 10 Pages: 2170-2186

    • DOI

      10.1038/s41388-019-1139-1

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A 23 gene-based molecular prognostic score precisely predicts overall survival of breast cancer patients2019

    • Author(s)
      Shimizu H, Nakayama KI
    • Journal Title

      EBioMedicine

      Volume: 46 Pages: 150-159

    • DOI

      10.1016/j.ebiom.2019.07.046

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Disruption of FBXL5-mediated cellular iron homeostasis promotes liver carcinogenesis2019

    • Author(s)
      Muto Yoshiharu*、Moroishi Toshiro*、Ichihara Kazuya、Nishiyama Masaaki、Shimizu Hideyuki、Eguchi Hidetoshi、Moriya Kyoji、Koike Kazuhiko、Mimori Koshi、Mori Masaki、Katayama Yuta、Nakayama Keiichi I. (*Equal contribution)
    • Journal Title

      The Journal of Experimental Medicine

      Volume: 216 Issue: 4 Pages: 950-965

    • DOI

      10.1084/jem.20180900

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Machine learning uncovers novel aspects in healthcare and life science2019

    • Author(s)
      清水秀幸
    • Organizer
      第42回 日本分子生物学会年会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] An AI-based Scoring System Precisely Predicts Overall Survival of Breast Cancer Patients2019

    • Author(s)
      清水秀幸
    • Organizer
      第14回研究所ネットワーク国際シンポジウム
    • Related Report
      2019 Research-status Report
    • Invited

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Published: 2019-04-18   Modified: 2022-01-27  

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