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Elucidation of the interaction between the pancreatic cancer-related microbiome and host gene mutations to achieve precision medicine

Research Project

Project/Area Number 22K15560
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 50020:Tumor diagnostics and therapeutics-related
Research InstitutionKyushu University

Principal Investigator

ABE Toshiya  九州大学, 大学病院, 助教 (20722028)

Project Period (FY) 2022-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2023: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2022: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords膵癌 / Microbiome / 遺伝子変異 / 個別化医療 / microbiome / 癌微小環境 / 膵癌周囲微小環境 / 次世代シーケンシング (NGS) / 腸内細菌叢
Outline of Research at the Start

膵癌は予後不良な疾患であり、その原因として膵癌に特徴的な周囲微小環境との癌間質相互作用が挙げられ、近年では腸内細菌や腫瘍内細菌との関連も報告されている。また膵癌は多様な体細胞遺伝子変異(KRAS、TP53など)を特徴とするがこれらをターゲットとした有効な治療法は存在せず、宿主の遺伝子変異と癌関連Microbiomeとの関係は不明である。本研究では、膵癌周囲の微小環境との癌間質相互作用に加えて、NGSを用いて膵癌組織の体細胞変異など後天的な遺伝子変異を解析することにより、これら遺伝子変異と膵癌の発癌や遠隔転移に促進的・抑制的に関わる腸内細菌や腫瘍内のMicrobiomeとの関連を明らかにする。

Outline of Final Research Achievements

Intratumor "F. nucleatum" promotes CXCL1 secretion from cancer cells, contributing to cancer progression in an autocrine and paracrine manners. The CXCL1-CXCR2 axis is activated by "F. nucleatum" to create an immunosuppressive tumor microenvironment, and blockade of this axis suppresses tumor growth. Our results suggest a novel therapeutic approach for intratumor "F. nucleatum"-positive pancreatic cancer patients.

Academic Significance and Societal Importance of the Research Achievements

今回腫瘍内の"F. nucleatum"が腫瘍微小環境を改変し腫瘍成長を促進させることを示した。口腔細菌叢は部分的に膵臓内の微生物叢を表していると考えられ、膵腫瘍内の細菌が悪性腫瘍に影響を与えることを考慮すると、口腔細菌叢の解析が膵癌の新たな治療法の開発に寄与する可能性がある。

Report

(3 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • Research Products

    (2 results)

All 2023

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

  • [Journal Article] Intratumor Fusobacterium nucleatum promotes the progression of pancreatic cancer via the CXCL1‐CXCR2 axis2023

    • Author(s)
      Hayashi Masataka、Ikenaga Naoki、Nakata Kohei、Luo Haizhen、Zhong PingShan、Date Satomi、Oyama Koki、Higashijima Nobuhiro、Kubo Akihiro、Iwamoto Chika、Torata Nobuhiro、Abe Toshiya、Yamada Yutaka、Ohuchida Kenoki、Oda Yoshinao、Nakamura Masafumi
    • Journal Title

      Cancer Science

      Volume: 114 Issue: 9 Pages: 3666-3678

    • DOI

      10.1111/cas.15901

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] BIOLOGICAL EFFECTS OF INTRATUMOR PERIODONTAL PATHOGENS IN PANCREATIC CANCER2023

    • Author(s)
      Masataka Hayashi, Naoki Ikenaga, Kohei Nakata, Haizhen Luo, PingShan Zhong, Koki Oyama, Nobuhiro Higashijima, Akihiro Kubo, Satomi Date, Chika Iwamoto, Kenoki Ohuchida, Masafumi
    • Organizer
      54th Annual American Pancreatic Association Meeting
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research

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Published: 2022-04-19   Modified: 2025-01-30  

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