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Analysis of microRNA in the cancer cell and stromal tissue to explore predictive biomarkers for the efficacy of vaccine treatment against colorectal cancer.

Research Project

Project/Area Number 17K16558
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Digestive surgery
Research InstitutionYamaguchi University

Principal Investigator

TAKENOUCHI Hiroko  山口大学, 医学部, 特別医学研究員 (20749808)

Research Collaborator HAZAMA Shoichi  
SUZUKI Nobuaki  
Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsマイクロRNA / 癌微小環境 / がん免疫療法 / バイオマーカー / 免疫学 / 臨床 / 遺伝子
Outline of Final Research Achievements

Many clinical trials of peptide vaccines have been conducted. However, these vaccines have provided clinical benefits in only a small fraction of patients. The purpose of this study was to explore microRNAs as novel predictive biomarkers for the efficacy of vaccine treatment against colorectal cancer. We conducted microarray analysis of cancer tissues in a phase II study, in which peptide vaccines combined with chemotherapy were given. Subsequently, we carried out RT-PCR analysis of phase II cases, separating cancer tissues into cancer cells and stromal tissue using laser capture microdissection. Treatment effect in relation to overall survival (OS) and miRNA expression was analyzed. Three miRNA predictors were negatively associated with OS: miR-125b-1 in cancer cells , and miR-378a in both cancer cells and stromal cells. In conclusion, miR-125b-1 and miR-378a expression might be considered as novel biomarkers to predict the efficacy of vaccine treatment against colorectal cancer.

Academic Significance and Societal Importance of the Research Achievements

がん免疫療法は近年注目され、開発が進んでいる領域であるが、免疫療法は患者によって効果に個人差があり、治療前にその効果を適切に予測できる方法の開発が重要である。
本研究では、Laser capture microdissection法により、がん組織をがん細胞と間質細胞に切り分け、各々のマイクロRNA発現量と免疫療法の治療効果との関連を解析したことで、がん細胞および間質部のmiR-125b-1ならびにmiR-378aが、免疫療法の効果と関連する有用なバイオマーカーとなり得る可能性を見出した。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (4 results)

All 2018 2017

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

  • [Journal Article] Overexpression of miR221 and miR222 in the cancer stroma is associated with malignant potential in colorectal cancer2018

    • Author(s)
      Iida Michihisa、Hazama Shoichi、Tsunedomi Ryouichi、Tanaka Hironori、Takenouchi Hiroko、Kanekiyo Shinsuke、Tokumitsu Yukio、Tomochika Shinobu、Tokuhisa Yoshihiro、Sakamoto Kazuhiko、Suzuki Nobuaki、Takeda Shigeru、Ueno Tomio、Yamamoto Shigeru、Yoshino Shigefumi、Fujita Koji、Kuroda Masahiko、Nagano Hiroaki
    • Journal Title

      Oncology Reports

      Volume: 40 Pages: 1621-1631

    • DOI

      10.3892/or.2018.6575

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] miR-125b-1 and miR-378a are predictive biomarkers for the efficacy of vaccine treatment against colorectal cancer2017

    • Author(s)
      Tanaka Hironori、Hazama Shoichi、Iida Michihisa、Tsunedomi Ryouichi、Takenouchi Hiroko、Nakajima Masao、Tokumitsu Yukio、Kanekiyo Shinsuke、Shindo Yoshitaro、Tomochika Shinobu、Tokuhisa Yoshihiro、Sakamoto Kazuhiko、Suzuki Nobuaki、Takeda Shigeru、Yamamoto Shigeru、Yoshino Shigefumi、Ueno Tomio、et. al.
    • Journal Title

      Cancer Science

      Volume: 108 Issue: 11 Pages: 2229-2238

    • DOI

      10.1111/cas.13390

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] miR-196b, miR-378a and miR-486 are predictive biomarkers for the efficacy of vaccine treatment in colorectal cancer2017

    • Author(s)
      Shindo Yoshitaro、Hazama Shoichi、Nakamura Yusuke、Inoue Yuka、Kanekiyo Shinsuke、Suzuki Nobuaki、Takenouchi Hiroko、Tsunedomi Ryouichi、Nakajima Masao、Ueno Tomio、Takeda Shigeru、Yoshino Shigefumi、Okuno Kiyotaka、Fujita Yusuke、Hamamoto Yoshihiko、Kawakami Yutaka、Oka Masaaki、Nagano Hiroaki
    • Journal Title

      Oncology Letters

      Volume: 14 Issue: 2 Pages: 1355-1362

    • DOI

      10.3892/ol.2017.6303

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 血清タンパク質網羅的解析による大腸癌新規予後マーカーの探索2018

    • Author(s)
      竹之内寛子、中島千代、硲彰一、兼清信介、中島正夫、松井洋人、北原正博、田中宏典、桑原太一、友近忍、飯田通久、徳久善弘、鈴木伸明、武田茂、山本滋、吉野茂文、荻原宏是、浜本義彦、上野富雄、永野浩昭
    • Organizer
      第39回癌免疫外科研究会
    • Related Report
      2018 Annual Research Report

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Published: 2017-04-28   Modified: 2020-03-30  

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