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Personalized cancer management based on microRNA biomarkers

Research Project

Project/Area Number 16K07146
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Tumor diagnostics
Research InstitutionFukushima Medical University

Principal Investigator

Ishigame Teruhide  福島県立医科大学, 医学部, 助教 (50583358)

Co-Investigator(Kenkyū-buntansha) 岡山 洋和  福島県立医科大学, 医学部, 講師 (20583397)
竹之下 誠一  福島県立医科大学, 医学部, 教授 (10167489)
千田 峻  福島県立医科大学, 医学部, 博士研究員 (40769642)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsマイクロRNA / 消化器癌 / 胃癌 / リンパ節転移
Outline of Final Research Achievements

Although this study originally aimed to investigate microRNAs that are specific to the lymph node involvement in gastric cancer, our microRNA screening strategies were not able to identify potential candidates. We then attempted to focus on the identification of microRNAs that regulate an immune checkpoint molecule, programmed cell death ligand 1 (PD-L1), since immunotherapy against the interaction between PD-1/PD-L1 has recently emerged as a promising strategy for gastrointestinal tract cancers. A comprehensive microRNA screening was conducted using The Cancer Genome Atlas (TCGA) dataset combined with microRNA target prediction programs, followed by the analysis of microarray-based mRNA/miRNA expression datasets and formalin-fixed paraffin-embedded (FFPE) samples by immunohistochemistry and qRT-PCR. Here we identified a tumor suppressive microRNA, miR-148a that can negatively regulate PD-L1, via direct binding to 3'UTR of PD-L1 mRNA.

Academic Significance and Societal Importance of the Research Achievements

マイクロRNAは標的遺伝子機能を制御することで発癌や癌の進展に重要な役割を担うことが知られている。癌診療においては、癌の診断、予後バイオマーカーや治療反応予測因子、さらに薬剤としての有用性が報告されているものもある。本研究で得られたマイクロRNAの機能や臨床的意義の知見が癌におけるマイクロRNAのさらなる理解や個別化医療の糸口へつながることが期待される。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (11 results)

All 2019 2018 2017

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Open Access: 2 results) Presentation (6 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] microRNA-148a-3p regulates immunosuppression in DNA mismatch repair-deficient colorectal cancer by targeting PD-L12019

    • Author(s)
      Ashizawa Mai、Okayama Hirokazu、Ishigame Teruhide、Thar Min Aung Kyi、Saito Katsuharu、Ujiie Daisuke、Murakami Yuko、Kikuchi Tomohiro、Nakayama Yuko、Noda Masaru、Tada Takeshi、Endo Hisahito、Fujita Shotaro、Sakamoto Wataru、Saito Motonobu、Saze Zenichiro、Momma Tomoyuki、Ohki Shinji、Mimura Kosaku、Kono Koji
    • Journal Title

      Molecular Cancer Research

      Volume: Epub ahead of print Issue: 6 Pages: 1403-1413

    • DOI

      10.1158/1541-7786.mcr-18-0831

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical significance of soluble intercellular adhesion molecule-1 and interleukin-6 in patients with extrahepatic cholangiocarcinoma2017

    • Author(s)
      Shimura T, Shibata M, Gonda K, Kofunato Y, Okada R, Ishigame T, Kimura T, Kenjo A, Marubashi S, Kono K, Takenoshita S
    • Journal Title

      Journal of Investigative Surgery

      Volume: 印刷中 Issue: 6 Pages: 475-482

    • DOI

      10.1080/08941939.2017.1358310

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] PD-L1 expression is mainly regulated by interferon gamma associated with JAK-STAT pathway in gastric cancer2017

    • Author(s)
      Mimura Kousaku、Teh Jun Liang、Okayama Hirokazu、Shiraishi Kensuke、Kua Ley-Fang、Koh Vivien、Smoot Duane T.、Ashktorab Hassan、Oike Takahiro、Suzuki Yoshiyuki、Fazreen Zul、Asuncion Bernadette R.、Shabbir Asim、Yong Wei-Peng、So Jimmy、Soong Richie、Kono Koji
    • Journal Title

      Cancer Science

      Volume: 109 Issue: 1 Pages: 43-53

    • DOI

      10.1111/cas.13424

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] CDX2 is involved in microRNA?associated inflammatory carcinogenesis in gastric cancer2017

    • Author(s)
      Saito Motonobu、Okayama Hirokazu、Saito Katsuharu、Ando Jin、Kumamoto Kensuke、Nakamura Izumi、Ohki Shinji、Ishi Yoshimasa、Takenoshita Seiichi
    • Journal Title

      Oncology Letters

      Volume: 14 Pages: 6184-6190

    • DOI

      10.3892/ol.2017.6956

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] ミスマッチ修復機構欠損を有する大腸癌におけるMicroRNAによるPD-L1制御機構2017

    • Author(s)
      芦澤舞、岡山洋和、Aung Kyi Thar Min、野田勝、青砥慶太、中島隆宏、石亀輝英、三村耕作、河野浩二
    • Journal Title

      癌と化学療法

      Volume: 44 Pages: 889-891

    • Related Report
      2017 Research-status Report
  • [Presentation] Identification of microRNAs that target PD-L1 in mismatch repair-deficient colorectal cancer2018

    • Author(s)
      Ashizawa M, Okayama H, Ishigame T, Mimura K, Kono K
    • Organizer
      ASCO-SITC CLINICAL IMMUNO-ONCOLOGY SYMPOSIUM
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Targeting the tumor microenvironment in dMMR/MSI-H colorectal cancer2018

    • Author(s)
      Okayama H, Ashizawa M, Kikuchi T, Sakamoto W, Fujita S, Endo H, Saito M, Momma T, Ohki S, Kono K
    • Organizer
      第73回日本消化器外科学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Identification of microRNAs that target PD-L1 in mismatch repair-deficient colorectal cancer2018

    • Author(s)
      芦澤舞,岡山洋和,石亀輝英,Thar Min Aung Kyi,氏家大輔,村上祐子,菊池智宏,野田勝,青砥慶太,中島隆宏,早瀬傑,坂本渉,藤田正太郎,遠藤久仁,齋藤元伸,門馬智之,佐瀬善一郎,三村耕作,大木進司,丸橋繁,河野浩二
    • Organizer
      第118回日本外科学会定期学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 胃癌患者における腫瘍内CD15/CD8陽性細胞比の臨床的意義2018

    • Author(s)
      渡邊 淳一郎, 木村 隆, 武藤 亮, 佐藤 直哉, 小船戸 康英, 石亀 輝英, 岡田 良, 見城 明, 志村 龍男, 河野 浩二, 丸橋 繁
    • Organizer
      日本外科学会定期学術集会 118回
    • Related Report
      2018 Annual Research Report
  • [Presentation] 脱フコシル化抗体を用いたADCCの検討2017

    • Author(s)
      中島 隆宏,河野 浩二,芦澤 舞,千田 峻,野田 勝,青砥 慶太,立花 和之進,岡山 洋和,早瀬 傑,坂本 渉,石亀 輝英,齋藤 元伸,志村 龍男,大竹 徹,竹之下 誠一
    • Organizer
      第117回日本外科学会定期学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] ミスマッチ修復機構欠損を有する大腸癌におけるmicroRNAによるPD-L1調整機構2017

    • Author(s)
      芦澤 舞,岡山 洋和,Min Aung Kyi Thar,野田 勝,青砥 慶太,中島 隆宏,石亀 輝英,円谷 彰,丸橋 繁,河野 浩二
    • Organizer
      第72回日本消化器外科学会総会
    • Related Report
      2017 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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