Development of the innovative new treatments targeting cancer metabolism utilizing large GI cancer cohorts

• Project/Area Number: 19K16750
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Kumamoto University
• Principal Investigator: KOSUMI Keisuke 熊本大学, 病院, 非常勤診療医師 (50594884)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 消化器癌 / 腫瘍微小環境 / がん代謝 / 腫瘍免疫 / マイクロバイオーム / バイオマーカー / ライフスタイル

Outline of Research at the Start

“がん代謝”は癌研究において非常に注目を集める研究領域である。近年の基礎研究で、がん代謝産物が腫瘍免疫に影響を与える事、微生物の代謝産物ががん代謝に利用される事が示唆された。腫瘍微小環境内で癌細胞・腫瘍免疫・微生物は複雑なネットワークを形成すると考えられ、それらを考慮した統合的解析が求められる。本研究の目的は、日・米の消化器癌データベースを対象に、がん代謝マーカー・腫瘍免疫・マイクロバイオームの網羅的解析を行い、腫瘍微小環境内におけるがん代謝の機能を解明する事である。また様々な臨床情報・生活情報と統合解析を行い、がん代謝を標的とする新規予後予測マーカー・治療法・癌予防法の開発への寄与を目指す。

Outline of Final Research Achievements

The aim of the current study is to contribute to the development of the innovative new treatments targeting cancer metabolism utilizing large GI cancer cohorts. We found that the amount of intratumoral Fusobacterium nucleatum DNA is associated with a diminished peritumoral lymphocytic reaction and peripheral lymphocyte. We also found the significant association between Fusobacterium nucleatum and LSD1 expression. Our findings support the possible influence of intratumoral Fusobacterium nucleatum on anti-tumor immunity and cancer metabolism.

Academic Significance and Societal Importance of the Research Achievements

本研究では、腫瘍微小環境においてがん代謝・腫瘍免疫・微生物がどのように関連し癌進展に寄与するかを明らかにすべく、グローバルかつ膨大な消化器癌データベースを用い検討を行った。腫瘍内Fusobacterium nucleatumが腫瘍免疫及びがん代謝に関連する可能性が示唆され、今後の発癌予防および免疫を介したがん治療に寄与できる可能性が示唆された。

Research Products

• [Journal Article] Patient Age and Long-term Survival in Colorectal Cancer Patients Who Undergo Emergency Surgery (2021)
  • Author(s): KOSUMI KEISUKE、MIMA KOSUKE、MORITO ATSUSHI、YUMOTO SHINSEI、MATSUMOTO TAKASHI、INOUE MITSUHIRO、MIZUMOTO TAKAO、KUBOTA TATSUO、MIYANARI NOBUTOMO、BABA HIDEO
  • Journal Title: Anticancer Research Volume: 41 Issue: 2 Pages: 1069-1076
  • DOI: 10.21873/anticanres.14864
  • Peer Reviewed
• [Journal Article] The microbiome, genetics, and gastrointestinal neoplasms: the evolving field of molecular pathological epidemiology to analyze the tumor?immune?microbiome interaction (2020)
  • Author(s): Mima Kosuke、Kosumi Keisuke、Baba Yoshifumi、Hamada Tsuyoshi、Baba Hideo、Ogino Shuji
  • Journal Title: Human Genetics Volume: － Issue: 5 Pages: 725-746
  • DOI: 10.1007/s00439-020-02235-2
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Significance of long-term surveillance for branch-duct intraductal papillary mucinous neoplasms from the perspective of molecular pathological epidemiology (2020)
  • Author(s): Kosumi Keisuke、Hayashi Hiromitsu、Baba Hideo
  • Journal Title: Annals of Translational Medicine Volume: 8 Issue: 15 Pages: 977-977
  • DOI: 10.21037/atm-20-2206
  • Peer Reviewed / Open Access
• [Journal Article] Frailty is an independent risk factor for recurrence and mortality after curative resection in patients with stage I-III colorectal cancer (2020)
  • Author(s): Mima K, Kurashige J, Miyanari N, Morito A, Yumoto S, Matsumoto T, Kosumi K, Inoue M, Mizumoto T, Kubota T, Baba H
  • Journal Title: Ann Gastroenterol Surg Volume: - Issue: 4 Pages: 405-412
  • DOI: 10.1002/ags3.12337
  • Peer Reviewed / Open Access
• [Journal Article] An integrated analysis of lymphocytic reaction, tumour molecular characteristics and patient survival in colorectal cancer (2020)
  • Author(s): Haruki K, Kosumi K (Co-first), Li P, Arima K, Väyrynen JP, Lau MC, Twombly TS, Hamada T, Glickman JN, Fujiyoshi K, Chen Y, Du C, Guo C, Väyrynen SA, Dias Costa A, Song M, Chan AT, Meyerhardt JA, Nishihara R, Fuchs CS, Liu L, Zhang X, Wu K, Giannakis M, Nowak JA, Ogino S
  • Journal Title: British Journal of Cancer Volume: 122(9) Issue: 9 Pages: 1367-1377
  • DOI: 10.1038/s41416-020-0780-3
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Metabolic Profiling of Formalin-Fixed Paraffin-Embedded Tissues Discriminates Normal Colon from Colorectal Cancer (2020)
  • Author(s): Arima K, Lau MC, Zhao M, Haruki K, Kosumi K, Mima K, Gu M, Väyrynen JP, Twombly TS, Baba Y, Fujiyoshi K, Kishikawa J, Guo C, Baba H, Richards WG, Chan AT, Nishihara R, Meyerhardt JA, Nowak JA, Giannakis M, Fuchs CS, Ogino S
  • Journal Title: Molecular Cancer Research Volume: - Issue: 6 Pages: 883-890
  • DOI: 10.1158/1541-7786.mcr-19-1091
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Association of autophagy status with amount of Fusobacterium nucleatum in colorectal cancer (2020)
  • 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
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Morphological lymphocytic reaction, patient prognosis and?PD‐1 expression after surgical resection for oesophageal cancer (2019)
  • 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
  • Peer Reviewed
• [Presentation] 高齢化社会を念頭においた大腸癌Oncologic emergency手術例の検討 (2020)
  • Author(s): 小澄敬祐, 森戸淳, 湯本信成, 松本嵩史, 美馬浩介, 井上光弘, 水元孝郎, 久保田竜生, 宮成信友, 馬場秀夫
  • Organizer: 第75回日本消化器外科学会総会
• [Presentation] Oncologic emergencyを伴う大腸癌緊急手術症例におけるDICの臨床学的意義 (2020)
  • Author(s): 小澄敬祐, 森戸淳, 湯本信成, 松本嵩史, 美馬浩介, 井上光弘, 水元孝郎, 久保田竜生, 宮成信友, 馬場秀夫
  • Organizer: 第28回日本消化器関連学会週間JDDW
• [Presentation] 食道癌における腫瘍内Fusobacterium nucleatumと腫瘍免疫の関連解析 (2019)
  • Author(s): 小澄敬祐, 馬場祥史, 山村謙介, 野元大地, 岡留一雄, 八木泰佑, 清住雄希, 江藤弘二郎, 日吉幸晴, 石本崇胤, 岩槻政晃, 長井洋平, 岩上志朗, 宮本裕士, 吉田直矢, 渡邊雅之, 馬場秀夫
  • Organizer: 第27回日本消化器関連学会週間 JDDW. 2019