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Development of clinical testing and precision medicine for early detection of risk, onset, and progression of refractory cancer

Research Project

Project/Area Number 23K27506
Project/Area Number (Other) 23H02815 (2023)
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeMulti-year Fund (2024)
Single-year Grants (2023)
Section一般
Review Section Basic Section 52010:General internal medicine-related
Research InstitutionShiga University of Medical Science

Principal Investigator

醍醐 弥太郎  滋賀医科大学, 医学部, 教授 (30345029)

Project Period (FY) 2024-04-01 – 2026-03-31
Project Status Granted (Fiscal Year 2024)
Budget Amount *help
¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000)
Fiscal Year 2025: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2024: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2023: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
Keywords迅速病態診断 / 精密医療
Outline of Research at the Start

本研究では胸部難治癌を解析モデルとして、その組織・血液試料とオミックス解析技術や血中微量核酸、蛋白の高精度分子検出技術を基盤として、「高精度の新規癌由来分子バイオマーカーの同定と検証」を行う。さらに、同定した複数のバイオマーカーに癌罹患性規定遺伝子の情報を統合することで「発癌リスクや未病・早期癌を検出し、その悪性度や分子病態を予測する統合的血液・組織診断法による先制プレシジョン医療の開発」に展開し、癌臨床検査の実装化モデルの構築を行う。

Outline of Annual Research Achievements

難治癌はヒト悪性腫瘍の多くを占め、早期診断や最適な治療選択が困難であり、低侵襲検査によるリスクと発症の早期検出と分子病態診断に基づいたプレシジョン医療(精密医療)に期待が集まっている。近年、腫瘍特異的に産生され癌悪性化に関わる分子を高精度に検出する超高感度ゲノム・プロテオーム解析技術が利用可能になってきており、一方、ゲノムワイド関連解析により、癌への罹りやすさを規定する癌罹患性規定遺伝子による発癌リスク機構が示されている。本研究では胸部難治癌を解析モデルとして、その組織・血液試料とオミックス解析技術や微量核酸、蛋白の高精度分子検出技術を基盤とした「高精度の新規癌由来分子バイオマーカーの同定と検証」を行い、さらに、同定した複数のバイオマーカーに癌罹患性規定遺伝子の情報を統合することで、癌罹患性や未病・早期癌を検出し、その悪性度や分子病態を予測する統合的診断法による先制プレシジョン医療の開発に展開した癌臨床検査を実装化することをめざした基盤整備と情報取得を行った。2024年度は、引き続き、定期的に本研究の探索的解析の結果と検証解析の進捗評価を行った。並行して、難治癌の臨床試料の遺伝子発現解析等による探索で選定された癌で特異的に高レベルに発現する分子のヒト癌組織における臨床病理学的意義を検証する目的で、遺伝子発現データベース解析や各分子に対する抗体と各種癌組織をスポットした詳細な臨床情報を備えた難治癌の組織マイクロアレイシステム等を使用した免疫組織化学染色を行い、癌患者群での発現分布(組織型、分化度、病期、予後との相関)を検討し、癌の悪性度に関与する組織バイオマーカーによる癌病態診断に資する基盤情報を入手した。

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

難治癌のオミックス解析情報に基づいたバイオマーカー候補の探索、解析を行うとともに、癌悪性度診断を含む難治癌の統合的診断系の構築に向けて、候補バイオマーカー分子の癌における発現の臨床病理学的意義を多数の癌組織を用いた解析で評価することにより基盤情報を取得できたため。

Strategy for Future Research Activity

引き続き難治癌のバイオマーカー候補につき多角的分子検出技術による解析を進めるとともに、次段階として、癌の統合的リスク・存在・病態診断法の構築に向けた基盤整備と分子解析を行う。

Report

(2 results)
  • 2024 Research-status Report
  • 2023 Annual Research Report
  • Research Products

    (12 results)

All 2024 2023

All Journal Article (11 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 11 results,  Open Access: 10 results) Presentation (1 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Journal Article] Expression of Lymphoid Enhancer-Binding Factor 1 in Cancer-Associated Fibroblasts Mediates Tumor Growth and Transdifferentiation Toward Squamous Cell Carcinoma in Human Breast Cancer2024

    • Author(s)
      Okazaki H, Mezawa Y, Shi Y, Sakimoto M, Wang Z, Takano A, Yokose T, Yamashita T, Miyagi Y, Daigo Y, Katakura A, Yasukawa T, Orimo A
    • Journal Title

      Cancer Medicine

      Volume: 14(3) Issue: 3

    • DOI

      10.1002/cam4.70627

    • Related Report
      2024 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Polygenic Risk Score and Lung Adenocarcinoma Risk Among Never-Smokers by EGFR Mutation Status: A Brief Report2024

    • Author(s)
      Blechter B, Hsiung CA, Wang X, Zhang H, Seow WJ, Shi J, Chatterjee N, Kim HN, Wong MP, Hong YC, Wong JYY, Dai J, Hosgood HD, Wang Z, Chang IS, Choi J et al
    • Journal Title

      J Thorac Oncol.

      Volume: - Issue: 4 Pages: 521-530

    • DOI

      10.1016/j.jtho.2024.11.019

    • Related Report
      2024 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Pre-existing autoimmune disease as a risk factor for immune-related adverse events in cancer patients receiving immune checkpoint inhibitors2024

    • Author(s)
      Hidetoshi Sumimoto, Atsushi Takano, Koji Teramoto, Satoshi Murata, Yataro Daigo
    • Journal Title

      PLoS One.

      Volume: 19(7) Issue: 7 Pages: e0306995-e0306995

    • DOI

      10.1371/journal.pone.0306995

    • Related Report
      2024 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Characterization of KIF20B as a novel prognostic biomarker and therapeutic target for breast cancer2024

    • Author(s)
      Regina Wachuka Mbugua, Atsushi Takano, Bayarbat Tsevegjav, Tomoyuki Yokose, Toshinari Yamashita, Yohei Miyagi, Yataro Daigo
    • Journal Title

      Int J Oncol.

      Volume: 64(4) Issue: 4 Pages: 43-43

    • DOI

      10.3892/ijo.2024.5631

    • Related Report
      2024 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Discrepancies Between Morphological and Immunohistochemical Classifications Are Associated With Prognoses and Subtypes of Lung Cancer2024

    • Author(s)
      NATSUME KOSUKE、YE JUANJUAN、MUKAI YURI、YAMAKAWA KEIKO、TANIMOTO MISA、ITO HIROYUKI、MIYAGI YOHEI、DAIGO YATARO、MUTO-ISHIZUKA MARIKO、KADOTA KYUICHI、HABA REIJI、SUIZU FUTOSHI
    • Journal Title

      Anticancer Research

      Volume: 44 Issue: 2 Pages: 711-722

    • DOI

      10.21873/anticanres.16862

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population2023

    • Author(s)
      Shi Jianxin、Shiraishi Kouya、et al.
    • Journal Title

      Nature Communications

      Volume: 14 Issue: 1 Pages: 3043-3043

    • DOI

      10.1038/s41467-023-38196-z

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Increased <scp>RUNX3</scp> expression mediates tumor‐promoting ability of human breast cancer‐associated fibroblasts2023

    • Author(s)
      Koyama Yu、Okazaki Hiroya、Shi Yang、Mezawa Yoshihiro、Wang Zixu、Sakimoto Mizuki、Ishizuka Akane、Ito Yasuhiko、Koyama Takumi、Daigo Yataro、Takano Atsushi、Miyagi Yohei、Yokose Tomoyuki、Yamashita Toshinari、Sugahara Keisuke、Hino Okio、Yang Liying、Maruyama Reo、Katakura Akira、Yasukawa Takehiro、Orimo Akira
    • Journal Title

      Cancer Medicine

      Volume: 12 Issue: 17 Pages: 18062-18077

    • DOI

      10.1002/cam4.6421

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prognostic impact of soluble PD-L1 derived from tumor-associated macrophages in non-small-cell lung cancer2023

    • Author(s)
      Teramoto Koji、Igarashi Tomoyuki、Kataoka Yoko、Ishida Mitsuaki、Hanaoka Jun、Sumimoto Hidetoshi、Daigo Yataro
    • Journal Title

      Cancer Immunology, Immunotherapy

      Volume: 72 Issue: 11 Pages: 3755-3764

    • DOI

      10.1007/s00262-023-03527-y

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Proteome analysis of CD5-positive diffuse large B cell lymphoma FFPE tissue reveals downregulation of DDX3X, DNAJB1, and B cell receptor signaling pathway proteins including BTK and Immunoglobulins2023

    • Author(s)
      Takuya Hiratsuka, Shinji Ito, Rika Sakai, Tomoyuki Yokose, Tatsuya Endo, Yataro Daigo, Yohei Miyagi, Tatsuaki Tsuruyama
    • Journal Title

      Clinical proteomics

      Volume: 20 Issue: 1 Pages: 36-36

    • DOI

      10.1186/s12014-023-09422-z

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Glutamine deficiency drives transforming growth factor‐β signaling activation that gives rise to myofibroblastic carcinoma‐associated fibroblasts2023

    • Author(s)
      Mezawa Yoshihiro、Wang Tingwei、Daigo Yataro、Takano Atsushi、Miyagi Yohei、Yokose Tomoyuki、Yamashita Toshinari、Yang Liying、Maruyama Reo、Seimiya Hiroyuki、Orimo Akira
    • Journal Title

      Cancer Science

      Volume: 114 Issue: 11 Pages: 4376-4387

    • DOI

      10.1111/cas.15955

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of telomere maintenance gene variations related to lung adenocarcinoma risk by genome‐wide association and whole genome sequencing analyses2023

    • Author(s)
      Shiraishi Kouya、Takahashi Atsushi、、et al.
    • Journal Title

      Cancer Communications

      Volume: 44 Issue: 2 Pages: 287-293

    • DOI

      10.1002/cac2.12498

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Integrated genomics-based discovery of new biomarkers and therapeutic targets for solid cancers.2023

    • Author(s)
      Yataro Daigo
    • Organizer
      The 25th International Charles Heidelberger Symposium on Cancer Research
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited

URL: 

Published: 2023-04-18   Modified: 2025-12-26  

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