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Comprehensive analysis of intestinal microbiomes affecting esophageal cancer chemotherapy

Research Project

Project/Area Number 19K18094
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 55020:Digestive surgery-related
Research InstitutionKumamoto University

Principal Investigator

YAGI Taisuke  熊本大学, 病院, 非常勤診療医師 (60836253)

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: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
KeywordsFusobacterium / 食道癌 / microbiome / 術前化学療法
Outline of Research at the Start

Microbiomeとは人体に生存する微生物群とその遺伝子および代謝活性の総称である。人体においては13兆のヒト細胞が130兆の細菌細胞と共存しており、また、2万のヒト遺伝子が、500万~800万の細菌遺伝子、いわゆるmicrobiomeと共存しており、化学療法の効果にも影響を及ぼすことが示唆されている。
食道がんにおける化学療法はある一定の効果が得られるものの、治療効果を予測するバイオマーカーの発見は急務と言える。食道がんにおける化学療法前後のmicrobiomeの変化、および特定のmicrobiomeが化学療法の治療効果につながるという仮説は我々のオリジナルであり独創的である。

Outline of Final Research Achievements

We have investigated the significance of Fusobacterium nucleatum in upper gastrointestinal cancer. In recent years, it has been reported that microbiome may affect anticancer drug sensitivity, and our esophageal cancer database also shows that the therapeutic effect of preoperative chemotherapy is poor in Fusobacterium nucleatum-positive cases. It was. Furthermore, the results of co-culture experiments between Fusobacterium nucleatum and esophageal cancer cell lines revealed that Fusobacterium nucleatum is involved in anticancer drug resistance by inducing autophagy. In future research, if the role of Fusobacterium nucleatum in the progression of esophageal cancer is elucidated in more detail, it may lead to new drug discovery for cancer treatment.

Academic Significance and Societal Importance of the Research Achievements

F. nucleatumは口腔内に常在するグラム陰性嫌気性桿菌で、歯周病や早産、炎症性腸疾患などの原因として知られている。F. nucleatumと食道がん細胞株との共培養実験の結果から、F. nucleatumがautophagyを誘導することにより抗がん剤抵抗性に関与していることが明らかとなった。F. nucleatumの役割がより詳細に解明されれば、がん治療の新たな創薬に繋がる可能性があると考える。

Report

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

    (8 results)

All 2021 2020 2019 2018 2017

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 1 results) Presentation (3 results) (of which Invited: 1 results)

  • [Journal Article] Prognostic impact of PD-1 on tumor infiltrating lymphocytes in 433 resected esophageal cancers2021

    • Author(s)
      Nomoto Daichi、Baba Yoshifumi、Okadome Kazuo、Yagi Taisuke、Kalikawe Rebecca、Kiyozumi Yuki、Harada Kazuto、Eto Kojiro、Hiyoshi Yukiharu、Nagai Yohei、Ishimoto Takatsugu、Iwatsuki Masaaki、Iwagami Shiro、Miyamoto Yuji、Yoshida Naoya、Komohara Yoshihiro、Watanabe Masayuki、Baba Hideo
    • Journal Title

      The Annals of Thoracic Surgery

      Volume: - Issue: 1 Pages: 286-294

    • DOI

      10.1016/j.athoracsur.2021.01.013

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prognostic and clinical impact of PD-L2 and PD-L1 expression in a cohort of 437 oesophageal cancers2020

    • Author(s)
      Okadome Kazuo、Baba Yoshifumi、Nomoto Daichi、Yagi Taisuke、Kalikawe Rebecca、Harada Kazuto、Hiyoshi Yukiharu、Nagai Yohei、Ishimoto Takatsugu、Iwatsuki Masaaki、Iwagami Shiro、Miyamoto Yuji、Yoshida Naoya、Watanabe Masayuki、Komohara Yoshihiro、Shono Takashi、Sasaki Yutaka、Baba Hideo
    • Journal Title

      British Journal of Cancer

      Volume: - Issue: 10 Pages: 1535-1543

    • DOI

      10.1038/s41416-020-0811-0

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Tumour-associated macrophages are associated with poor prognosis and programmed death ligand 1 expression in oesophageal cancer2019

    • Author(s)
      Yagi Taisuke、Baba Yoshifumi、Okadome Kazuo、Kiyozumi Yuki、Hiyoshi Yukiharu、Ishimoto Takatsugu、Iwatsuki Masaaki、Miyamoto Yuji、Yoshida Naoya、Watanabe Masayuki、Komohara Yoshihiro、Baba Hideo
    • Journal Title

      European Journal of Cancer

      Volume: 111 Pages: 38-49

    • DOI

      10.1016/j.ejca.2019.01.018

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Progress in characterizing the linkage between Fusobacterium nucleatum and gastrointestinal cancer2018

    • Author(s)
      Liu Yang、Baba Yoshifumi、Ishimoto Takatsugu、Iwatsuki Masaaki、Hiyoshi Yukiharu、Miyamoto Yuji、Yoshida Naoya、Wu Rong、Baba Hideo
    • Journal Title

      Journal of Gastroenterology

      Volume: 54 Issue: 1 Pages: 33-41

    • DOI

      10.1007/s00535-018-1512-9

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] PD-L1 Expression, Tumor-infiltrating Lymphocytes, and Clinical Outcome in Patients With Surgically Resected Esophageal Cancer.2017

    • Author(s)
      Yagi T, Baba Y, Ishimoto T, Iwatsuki M, Miyamoto Y, Yoshida N, Watanabe M, Baba H.
    • Journal Title

      Ann Surg.

      Volume: Dec 4 Issue: 3 Pages: 471-478

    • DOI

      10.1097/sla.0000000000002616

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 胃癌におけるT cell inflamed gene expression signatureを用いたphenotypeの解析2020

    • Author(s)
      八木泰佑、中村健一、畠山慶一、古川健一朗、藤谷啓一、神谷諭、日景允、谷澤豊、坂東悦郎、山口建、寺島雅典
    • Organizer
      第31回日本消化器癌発生学会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 食道癌におけるPD-1陽性腫瘍浸潤リンパ球の意義2019

    • Author(s)
      八木泰佑、馬場祥史、岡留一雄、内原智幸、古閑悠輝、清住雄希、江藤弘二郎、日吉幸晴、岩槻政晃、石本崇胤、岩上志朗、宮本裕士、吉田直矢、馬場秀夫
    • Organizer
      日本外科学会
    • Related Report
      2019 Research-status Report
  • [Presentation] The significance of PD-1 expression in the tumor invasive marigin in patients with esophageal cancer2019

    • Author(s)
      八木泰佑、馬場祥史、岡留一雄、内原智幸、古閑悠輝、清住雄希、江藤弘二郎、日吉幸晴、岩槻政晃、石本崇胤、岩上志朗、宮本裕士、吉田直矢、馬場秀夫
    • Organizer
      日本消化器外科学会
    • Related Report
      2019 Research-status Report

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

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