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The biological and clinical significance of the novel GC oncogenes that were identified by in silico analysis

Research Project

Project/Area Number 19K16718
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 50010:Tumor biology-related
Research InstitutionKyushu University

Principal Investigator

HU Qingjiang  九州大学, 大学病院, 助教 (80792902)

Project Period (FY) 2019-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords胃癌 / 腫瘍学 / CYT / LOXL1 / OSBPL3 / 免疫チェックポイント / 癌遺伝子 / 腫瘍局所環境 / 増殖能 / 細胞周期 / RRAS / RNA-seq / in silico解析 / Xenograft mouse / 新規癌遺伝子 / 新規治療標的 / NGS解析
Outline of Research at the Start

主に初年度でOSBPL3の遺伝子操作を行い、OSBPL3の表現型を明らかにする。複数の胃癌細胞株でOSBPL3の過剰発現細胞株とノックアウト細胞株を樹立し、癌進展に必要な増殖能、 遊走能、浸潤能を評価する。複数の系で実験を行い、細胞周期および細胞死との関連も合わせて検討する。また当院の胃癌組織を用いて免疫染色し、OSBPL3の臨床的意義を明らかにする。
主に次年度でOSBPL3のメカニズムを検討する。OSBPL3の遺伝子操作細胞株のRNAシーケンスデータを用いてpathway解析を行う。関連するpathwayを実験で検証する。臨床応用研究の橋渡しとしてOSBPL3の阻害薬を同定する。

Outline of Final Research Achievements

We identified LOXL1 as a candidate gene responsible for peritoneal dissemination of gastric cancer and reported it in a paper. We clarified the clinical significance of the CYT score, which reflects the local immune environment of gastric cancer, and reported it in a paper. We experienced a rare adverse event of nivolumab therapy in gastric cancer, and reported it in a paper. Furthermore, we identified OSBPL3 as a novel oncogene, and clarified its biological and clinical significance in gastric cancer.

Academic Significance and Societal Importance of the Research Achievements

胃癌進行の責任遺伝子を同定することで、その根底にあるメカニズムを明らかにし、新たな胃癌の治療法と検査法の開発につながります。胃癌の予後改善に寄与することが予想されます。
また、胃癌における免疫療法が盛んに研究されていますが、その治療効果予測因子が少ない現状です。我々はCYT scoreが胃癌局所免疫を反映することを証明し、免疫療法の治療効果予測因子になりうることを提示しました。これも胃癌の予後改善に寄与することが予想されます。

Report

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

    (7 results)

All 2021 2020 2019

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (4 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Cytolytic activity score as a biomarker for antitumor immunity and clinical outcome in patients with gastric cancer2021

    • Author(s)
      Qingjiang Hu 1 , Kentaro Nonaka 1 , Hiroaki Wakiyama 2 , Yu Miyashita 1 , Yoshiaki Fujimoto 1 , Tomoko Jogo 1 , Kentaro Hokonohara 1 , Ryota Nakanishi 1 , Yuichi Hisamatsu 1 , Koji Ando 1 , Yasue Kimura 1 , Takaaki Masuda 2 , Eiji Oki 1 , Koshi Mimori 2 , Yoshinao Oda 3 , Masaki Mori 1
    • Journal Title

      Cancer Med.

      Volume: - Issue: 9 Pages: 3129-3138

    • DOI

      10.1002/cam4.3828

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Potential association of LOXL1 with peritoneal dissemination in gastric cancer via promotion of EMT2020

    • Author(s)
      Hu, Q, Masuda T et al
    • Journal Title

      PloS ONE

      Volume: 15 Issue: 10 Pages: e0241140-e0241140

    • DOI

      10.1371/journal.pone.0241140

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Reintroduction of nivolumab in a patient with gastric cancer after improvement of nivolumab-induced acute interstitial nephritis: a case report2020

    • Author(s)
      Qingjiang Hu 1 , Hirofumi Hasuda 1 , Kenji Ueki 2 , Akihiro Tsuchimoto 2 , Yoko Zaitsu 1 , Yasuo Tsuda 1 , Yuichi Hisamatsu 1 , Yuichiro Nakashima 1 , Koji Ando 1 , Yasue Kimura 1 , Eiji Oki 1 , Masaki Mori 1
    • Journal Title

      Int Cancer Conf J.

      Volume: 9 Issue: 3 Pages: 127-132

    • DOI

      10.1007/s13691-020-00418-2

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Presentation] 当科での使用経験から見た胃癌に対するニボルマブの臨床意義2021

    • Author(s)
      蓮田 博文、胡 慶江
    • Organizer
      第76回消化器外科学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] LOXL1 is a novel responsible gene for peritoneal dissemination potentially via promoting EMT and motility in gastric cancer2020

    • Author(s)
      Qingjiang Hu
    • Organizer
      AACR
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Potential association of LOXL1 with peritoneal dissemination in gastric cancer via promotion of EMT2020

    • Author(s)
      胡 慶江
    • Organizer
      第120回日本外科学会
    • Related Report
      2019 Research-status Report
  • [Presentation] LOXL1 is a novel responsible gene for peritoneal dissemination potentially via promoting EMT and motility in gastric cancer2019

    • Author(s)
      Qingjiang Hu
    • Organizer
      7th international Conference of Federation of Asian Clinical Oncology (FACO)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research

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

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