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Comprehensive analysis of gut microbiome and epigenetic changes in esophageal cancer.

Research Project

Project/Area Number 17H04273
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionKumamoto University

Principal Investigator

Baba Yoshifumi  熊本大学, 病院, 非常勤診療医師 (20599708)

Co-Investigator(Kenkyū-buntansha) 美馬 浩介  熊本大学, 病院, 非常勤診療医師 (00546559)
澤 智裕  熊本大学, 大学院生命科学研究部(医), 教授 (30284756)
吉田 直矢  熊本大学, 病院, 特任准教授 (60467983)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2019: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2018: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2017: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Keywords腸内細菌叢 / LINE-1 / 食道癌 / 腫瘍免疫 / Fusobacterium / microbiome / 16S rRNA シークエンス / LNE-1 / Fusobacterium nucleatum / epigenetics / esophageal cancer
Outline of Final Research Achievements

Fusobacterium nucleatum (F. nucleatum), which primarily inhabits the oral cavity, causes periodontal disease. F. nucleatum influences the development and progression of esophageal cancer. First, we showed that F. nucleatum tumors had lower LINE-1 methylation level (global DNA methylation). Second, we could demonstrate that LINE-1 hypomethylation was associated with LINE-1 copy number in esophageal cancers. Third, we found that tumor LINE-1 hypomethylation level was associated with a diminished peritumoral lymphocytic reaction.

Academic Significance and Societal Importance of the Research Achievements

腸内細菌叢microbiomeは薬剤などにより後天的に変化させうるものであり、疾患治療のターゲットとしてもきわめて有望である。よって、“Fusobacteriumという口腔内に存在する菌が、食道癌のメチル化や腫瘍免疫に関与する”という今回得られた結果は臨床応用に直結する可能性があり、創薬へ向けた橋渡し研究として極めて意義深いものである。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (19 results)

All 2020 2019 2018 2017

All Journal Article (12 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 12 results,  Open Access: 2 results) Presentation (7 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Mucosal cancer-associated microbes and anastomotic leakage after resection of colorectal carcinoma2020

    • Author(s)
      Mima Kosuke、Sakamoto Yuki、Kosumi Keisuke、Ogata Yoko、Miyake Keisuke、Hiyoshi Yukiharu、Ishimoto Takatsugu、Iwatsuki Masaaki、Baba Yoshifumi、Iwagami Shiro、Miyamoto Yuji、Yoshida Naoya、Ogino Shuji、Baba Hideo
    • Journal Title

      Surgical Oncology

      Volume: 32 Pages: 63-68

    • DOI

      10.1016/j.suronc.2019.11.005

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Association of autophagy status with amount of Fusobacterium nucleatum in colorectal cancer2020

    • Author(s)
      Haruki K, Kosumi K, Hamada T, Twombly TS, Väyrynen JP, et al.
    • Journal Title

      The Journal of Pathology

      Volume: 250 Issue: 4 Pages: 397-408

    • DOI

      10.1002/path.5381

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [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
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Morphological lymphocytic reaction, patient prognosis and?PD‐1 expression after surgical resection for oesophageal cancer2019

    • Author(s)
      Baba Y.、Yagi T.、Kosumi K.、Okadome K.、Nomoto D.、Eto K.、Hiyoshi Y.、Nagai Y.、Ishimoto T.、Iwatsuki M.、Iwagami S.、Miyamoto Y.、Yoshida N.、Komohara Y.、Watanabe M.、Baba H.
    • Journal Title

      BJS

      Volume: 106 Issue: 10 Pages: 1352-1361

    • DOI

      10.1002/bjs.11301

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tumor Long-interspersed Nucleotide Element-1 Methylation Level and Immune Response to Esophageal Cancer2019

    • Author(s)
      Kosumi Keisuke、Baba Yoshifumi、Okadome Kazuo、Yagi Taisuke、Kiyozumi Yuki、Yoshida Naoya、Watanabe Masayuki、Baba Hideo
    • Journal Title

      Annals of Surgery

      Volume: - Issue: 6 Pages: 1-1

    • DOI

      10.1097/sla.0000000000003264

    • Related Report
      2019 Annual Research 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 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intratumoral Fusobacterium Nucleatum Levels Predict Therapeutic Response to Neoadjuvant Chemotherapy in Esophageal Squamous Cell Carcinoma2019

    • Author(s)
      Yamamura Kensuke、Izumi Daisuke、Kandimalla Raju、Sonohara Fuminori、Baba Yoshifumi、Yoshida Naoya、Kodera Yasuhiro、Baba Hideo、Goel Ajay
    • Journal Title

      Clinical Cancer Research

      Volume: 25 Issue: 20 Pages: 6170-6179

    • DOI

      10.1158/1078-0432.ccr-19-0318

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Lysyl oxidase impacts disease outcomes and correlates with global DNA hypomethylation in esophageal cancer2019

    • Author(s)
      Kalikawe Rebecca、Baba Yoshifumi、Nomoto Daichi、Okadome Kazuo、Miyake Keisuke、Eto Kojiro、Hiyoshi Yukiharu、Nagai Youhei、Iwatsuki Masaaki、Ishimoto Takatsugu、Iwagami Shiro、Miyamoto Yuji、Yoshida Naoya、Watanabe Masayuki、Baba Hideo
    • Journal Title

      Cancer Science

      Volume: 110 Issue: 12 Pages: 3727-3737

    • DOI

      10.1111/cas.14214

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prognostic Nutritional Index, Tumor-infiltrating Lymphocytes, and Prognosis in Patients with Esophageal Cancer2018

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

      Annals of Surgery

      Volume: 271 Issue: 4 Pages: 1-1

    • DOI

      10.1097/sla.0000000000002985

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] IDO1 Expression Is Associated With Immune Tolerance and Poor Prognosis in Patients With Surgically Resected Esophageal Cancer.2018

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

      Ann Surg

      Volume: Mar 27 Issue: 6 Pages: 1-1

    • DOI

      10.1097/sla.0000000000002754

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [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
      2018 Annual Research 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
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 食道癌コホートを用いたFusobacterium nucleatumと腫瘍免疫の統合解析2019

    • Author(s)
      小澄敬祐、馬場祥史、山村謙介、岡留一雄、八木泰佑、清住雄希、岩槻政晃、長井洋平、吉田直矢、馬場秀夫
    • Organizer
      第74回日本消化器外科学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Fusobacterium nucleatumの食道癌進展への関与とそのメカニズム;腫瘍免疫、NF-kB経路との関連2019

    • Author(s)
      野元大地、馬場祥史、秋山貴彦、岡留一雄、山下晃平、坂本悠樹、大徳暢哉、織田枝里、内原智幸、徳永竜馬、原田和人、山村謙介、江藤弘二郎、日吉幸晴、長井洋平、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
      第30回日本消化器癌発生学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 個別化治療を目指したLINE-1メチル化レベル解析:予後予測、早期診断、免疫チェックポイント阻害剤のbiomarkerとしての可能性2018

    • Author(s)
      馬場祥史、岡留一雄、八木泰佑、黒田大介、澤山浩、日吉幸晴、岩槻政晃、石本崇胤、宮本裕士、吉田直矢、馬場秀夫
    • Organizer
      第118回日本外科学会定期学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] LINE-1 methylation level and local immune response in esophageal cancer2018

    • Author(s)
      Yoshifumi Baba、Keisuke Kosumi, Daichi Nomoto, Kazuo Okadome, Taisuke Yagi, Yuki Kiyozumi, Kojiro Eto, Yukiharu Hiyoshi, Takatsugu Ishimoto, Masaaki Iwatsuki, Shiro Iwagami, Yuji Miyamoto, Naoya Yoshida, Hideo Baba
    • Organizer
      The International Society for Disease of the Esophagus(ISDE)
    • Related Report
      2018 Annual Research Report
  • [Presentation] 食道癌におけるLINE-1メチル化と腫瘍免疫2018

    • Author(s)
      馬場祥史、小澄敬祐、岡留一雄、八木泰佑、清住雄希、江藤弘二郎、日吉幸晴、長井洋平、石本崇胤、岩上志朗、宮本裕士、吉田直矢、馬場秀夫
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 腸内細菌 Fusobacterium nucleatumは食道癌に対する化学療法感受性に影響を与える2018

    • Author(s)
      馬場祥史、山村謙介、江藤弘二郎、日吉幸晴、長井洋平、岩槻政晃、岩上志朗、宮本裕士、吉田直矢、馬場秀夫
    • Organizer
      第56回日本癌治療学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] The relationship between Microbiome Fusobacterium Nucleatum and autophagy in esophageal cancer2018

    • Author(s)
      Liu Yang, Yoshifumi Baba, Shigeki Nakagawa, Hiroshi Sawayama, Takatsugu Ishimoto, Masaaki Iwatsuki, Yuji Miyamoto , Yoichi Yamashita, Naoya Yoshida, Hideo Baba
    • Organizer
      Association for Cancer Research 2018
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research

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Published: 2017-04-28   Modified: 2021-02-19  

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