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Maximizing diagnostic performance using information on the shell and contents of extracellular vesicles specific to pancreatic cancer stem cells

Research Project

Project/Area Number 21K19526
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 55:Surgery of the organs maintaining homeostasis and related fields
Research InstitutionOsaka University

Principal Investigator

Ishii Hideshi  大阪大学, 大学院医学系研究科, 招へい教授 (10280736)

Co-Investigator(Kenkyū-buntansha) 江口 英利  大阪大学, 大学院医学系研究科, 教授 (90542118)
Project Period (FY) 2021-07-09 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2023: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2022: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2021: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords膵がん / RNA修飾 / 細胞外小胞 / エクソソーム / がん幹細胞 / エク ソソーム
Outline of Research at the Start

本計画では、標準的な方法を凌駕する画期的な新技術を開発するために、腫瘍の根源となる「がん幹細胞」を分離培養し、そこから分泌される「細胞外小胞」の『中身』の①増殖(RNA配列)と②代謝(RNAメチル化)に加えて、『殻』の脂質二重膜として、③組織と④分化の情報を加えた4要素を粒子レベルで把握し、がんの生物学的な悪性度を最高レベルの解像度で理解できる革新的な技術を開発する。もって、従来法では解決できなかった膵がんの薬剤耐性や転移性と密接に関連する分子の情報を明らかにして、膵がんの診断性能を最大化する。3年間で早期の膵がん計120例の症例を蓄積して検討し、計測系を最適化する。

Outline of Final Research Achievements

In this groundbreaking study, we have developed innovative techniques aimed at the early detection of pancreatic cancer by isolating and culturing the "cancer stem cells," the origin of tumors, enabling us to comprehend the biological malignancy of cancer at the highest resolution. As a result, we have identified characteristic RNA methylation target genes associated with the properties of extracellular vesicles, corresponding to pancreatic cancer. We are advancing the development of these findings as intellectual property of Osaka University, while also proceeding with the publication of experimental techniques through papers and presentations at academic conferences. Consequently, we have laid the foundation for biomarker establishment towards the profiling of cancer stem cells via liquid biopsy of extracellular vesicles in peripheral blood.

Academic Significance and Societal Importance of the Research Achievements

「がん幹細胞」の機能と存在を精密に診断するために、腫瘍の根源となる「がん幹細胞」を分離培養し、そこから分泌される「細胞外小胞」の『中身』の1増殖(RNA配列)と2代謝(RNAメチル化)に加えて、『殻』の脂質二重膜として、組織と分化の情報を加えた4要素を粒子レベルで把握し、がんの生物学的 な悪性度を最高レベルの解像度で理解できる革新的な技術を開発した。知的財産として整備を進め、実験的な技術のノウハウに関しては論文及び学会発表で公表した。 このように、本研究において微細な細胞外分泌小胞の性状に基づくがん幹細胞のプロファイリングに向けて、技術を改善させてバイオマーカーの基盤を構築することができた。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (31 results)

All 2024 2023 2022 2021

All Journal Article (22 results) (of which Int'l Joint Research: 12 results,  Peer Reviewed: 22 results,  Open Access: 21 results) Presentation (9 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] RNA methylation in inflammatory bowel disease2024

    • Author(s)
      Ozato Yuki、Hara Tomoaki、Meng Sikun、Sato Hiromichi、Tatekawa Shotaro、Uemura Mamoru、Yabumoto Takeshi、Uchida Shizuka、Ogawa Kazuhiko、Doki Yuichiro、Eguchi Hidetoshi、Ishii Hideshi
    • Journal Title

      Cancer Science

      Volume: 115 Issue: 3 Pages: 723-733

    • DOI

      10.1111/cas.16048

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Significance of signal recognition particle 9: implications for pancreatic cancer prognosis and functionality2024

    • Author(s)
      Sato Hiromichi、Meng Sikun、Sasaki Kazuki 、Kobayashi Shogo、Kido Kensuke、Tsuji Yoshiko、Arao Yasuko、Saito Yoshiko、Doki Yuichiro、Eguchi Hidetoshi、Hara Tomoaki、Ishii Hideshi
    • Journal Title

      International Journal of Molecular Oncology

      Volume: -

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fat and proteolysis due to methionine, tryptophan, and niacin deficiency leads to alterations in gut microbiota and immune modulation in inflammatory bowel disease2024

    • Author(s)
      Hara Tomoaki、 MengSikun、 Motooka Daisuke、Sato Hiromichi、Arao Yasuko、Tsuji Yoshiko、Yabumoto Takeshi、Doki Yuichiro、 Eguchi Hidetoshi、Uchida Shizuka、Ishii Hideshi
    • Journal Title

      Cancer Science

      Volume: -

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] High N6-methyladenosine-activated TCEAL8 mRNA is a novel pancreatic cancer marker2024

    • Author(s)
      Hara Tomoaki、Meng Sikun、Sato Hiromichi et al.
    • Journal Title

      Cancer Science

      Volume: - Issue: 7 Pages: 2360-2370

    • DOI

      10.1111/cas.16152

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] RN7SL1 may be translated under oncogenic conditions2024

    • Author(s)
      Hara Tomoaki、Meng Sikun、Tsuji Yoshiko、Arao Yasuko、Saito Yoshiko、Sato Hiromichi、Motooka Daisuke、Uchida Shizuka、Ishii Hideshi
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 121 Issue: 12

    • DOI

      10.1073/pnas.2312322121

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] T2DB: A Web Database for Long Non-Coding RNA Genes in Type II Diabetes2023

    • Author(s)
      Distefano Rebecca、Ilieva Mirolyuba、Madsen Jens Hedelund、Ishii Hideshi、Aikawa Masanori、Rennie Sarah、Uchida Shizuka
    • Journal Title

      Non-Coding RNA

      Volume: 9 Issue: 3 Pages: 30-30

    • DOI

      10.3390/ncrna9030030

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Systematic analysis and characterization of long non-coding RNA genes in inflammatory bowel disease2023

    • Author(s)
      Velissari Rania、Ilieva Mirolyuba、Dao James、Miller Henry E、Madsen Jens Hedelund、Gorodkin Jan、Aikawa Masanori、Ishii Hideshi、Uchida Shizuka
    • Journal Title

      Briefings in Functional Genomics

      Volume: ‐ Issue: 4 Pages: 395-405

    • DOI

      10.1093/bfgp/elad044

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The Link of mRNA and rRNA Transcription by PUF60/FIR through TFIIH/P62 as a Novel Therapeutic Target for Cancer2023

    • Author(s)
      Kitamura Kouichi、Hoshino Tyuji、Okabe Atsushi、Fukuyo Masaki、Rahmutulla Bahityar、Tanaka Nobuko、Kobayashi Sohei、Tanaka Tomoaki、Shida Takashi、Ueda Mashiro、Minamoto Toshinari、Matsubara Hisahiro、Kaneda Atsushi、Ishii Hideshi、Matsushita Kazuyuki
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 24 Issue: 24 Pages: 17341-17341

    • DOI

      10.3390/ijms242417341

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cancer-specific tissue-resident memory T-cells express ZNF683 in colorectal cancer2023

    • Author(s)
      Kitakaze Masatoshi、Uemura Mamoru、Hara Tomoaki、Chijimatsu Ryota、Motooka Daisuke、Hirai Toshiro、Konno Masamitsu、Okuzaki Daisuke、Sekido Yuki、Hata Tsuyoshi、Ogino Takayuki、Takahashi Hidekazu、Miyoshi Norikatsu、Ofusa Ken、Mizushima Tsunekazu、Eguchi Hidetoshi、Doki Yuichiro、Ishii Hideshi
    • Journal Title

      British Journal of Cancer

      Volume: - Issue: 10 Pages: 1828-1837

    • DOI

      10.1038/s41416-023-02202-4

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Direct observation of DNA alterations induced by a DNA disruptor2022

    • Author(s)
      Ohshiro Takahito、Asai Ayumu、Konno Masamitsu、Ohkawa Mayuka、Komoto Yuki、Ofusa Ken、Ishii Hideshi、Taniguchi Masateru
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 6945-6945

    • DOI

      10.1038/s41598-022-10725-8

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] N(6)-methyladenosine methylation-regulated polo-like kinase 1 cell cycle homeostasis as a potential target of radiotherapy in pancreatic adenocarcinoma2022

    • Author(s)
      Tatekawa Shotaro、Tamari Keisuke、Chijimatsu Ryota、Konno Masamitsu、Motooka Daisuke、Mitsufuji Suguru、Akita Hirofumi、Kobayashi Shogo、Murakumo Yoshiki、Doki Yuichiro、Eguchi Hidetoshi、Ishii Hideshi、Ogawa Kazuhiko
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 11074-11074

    • DOI

      10.1038/s41598-022-15196-5

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Establishment of a reference single-cell RNA sequencing dataset for human pancreatic adenocarcinoma2022

    • Author(s)
      Chijimatsu R、Kobayashi S、Takeda Y、Kitakaze M、Tatekawa S、Tachibana N、Saito T、Ennishi D、Tomida S、Sasaki K、Yamada D、Tomimaru Y、Takahashi H、Doki Y、Eguchi H
    • Journal Title

      iScience

      Volume: 25 Issue: 8 Pages: 104659-104659

    • DOI

      10.1016/j.isci.2022.104659

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Circulating cancer‐associated extracellular vesicles as early detection and recurrence biomarkers for pancreatic cancer2022

    • Author(s)
      Yoshioka Yusuke、Shimomura Manami、Saito Keigo、Ishii Hideshi、Doki Yuichiro、Eguchi Hidetoshi、Nakatsura Tetsuya、Itoi Takao、Kuroda Masahiko、Mori Masaki、Ochiya Takahiro
    • Journal Title

      Cancer Science

      Volume: 113 Issue: 10 Pages: 3498-3509

    • DOI

      10.1111/cas.15500

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cancer metabolism challenges genomic instability and clonal evolution as therapeutic targets2022

    • Author(s)
      Takeda Yu、Chijimatsu Ryota、Ofusa Ken、Kobayashi Shogo、Doki Yuichiro、Eguchi Hidetoshi、Ishii Hideshi
    • Journal Title

      Cancer Science

      Volume: 113 Issue: 4 Pages: 1097-1104

    • DOI

      10.1111/cas.15279

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nematode-applied technology for human tumor microenvironment research and development2022

    • Author(s)
      Luccio Eric、Kaifuchi Satoru、 Kondo Nobuaki、Chijimatsu Ryota、 Vecchione Andrea、 Hirotsu Takaaki、 Ishii Hideshi
    • Journal Title

      Current Issues in Molecular Biology

      Volume: ー

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Clinicopathological significance of <scp>MYL9</scp> expression in pancreatic ductal adenocarcinoma2021

    • Author(s)
      Matsushita Katsunori、Kobayashi Shogo、Akita Hirofumi、Konno Masamitsu、Asai Ayumu、Noda Takehiro、Iwagami Yoshifumi、Asaoka Tadafumi、Gotoh Kunihito、Mori Masaki、Doki Yuichiro、Eguchi Hidetoshi、Ishii Hideshi
    • Journal Title

      Cancer Reports

      Volume: - Issue: 10

    • DOI

      10.1002/cnr2.1582

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Computational healthcare: Present and future perspectives (Review)2021

    • Author(s)
      Asai Ayumu、Konno Masamitsu、Taniguchi Masateru、Vecchione Andrea、Ishii Hideshi
    • Journal Title

      Experimental and Therapeutic Medicine

      Volume: 22 Issue: 6 Pages: 1351-1351

    • DOI

      10.3892/etm.2021.10786

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Methylosystem for Cancer Sieging Strategy2021

    • Author(s)
      Tatekawa Shotaro、Ofusa Ken、Chijimatsu Ryota、Vecchione Andrea、Tamari Keisuke、Ogawa Kazuhiko、Ishii Hideshi
    • Journal Title

      Cancers

      Volume: 13 Issue: 20 Pages: 5088-5088

    • DOI

      10.3390/cancers13205088

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Single-molecule RNA sequencing for simultaneous detection of m6A and 5mC2021

    • Author(s)
      Ohshiro Takahito、Konno Masamitsu、Asai Ayumu、Komoto Yuki、Yamagata Akira、Doki Yuichiro、Eguchi Hidetoshi、Ofusa Ken、Taniguchi Masateru、Ishii Hideshi
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 19304-19304

    • DOI

      10.1038/s41598-021-98805-z

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Epithelial Cell Transformation and Senescence as Indicators of Genome Aging: Current Advances and Unanswered Questions2021

    • Author(s)
      Kitakaze Masatoshi、Chijimatsu Ryota、Vecchione Andrea、Kitagawa Toru、Doki Yuichiro、Eguchi Hidetoshi、Ishii Hideshi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 14 Pages: 7544-7544

    • DOI

      10.3390/ijms22147544

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Scent test using Caenorhabditis elegans to screen for early-stage pancreatic cancer2021

    • Author(s)
      Asai Ayumu、Konno Masamitsu、Ozaki Miyuki、Kawamoto Koichi、Chijimatsu Ryota、Kondo Nobuaki、Hirotsu Takaaki、Ishii Hideshi
    • Journal Title

      Oncotarget

      Volume: 12 Issue: 17 Pages: 1687-1696

    • DOI

      10.18632/oncotarget.28035

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Impact of One-Carbon Metabolism-Driving Epitranscriptome as a Therapeutic Target for Gastrointestinal Cancer2021

    • Author(s)
      Takeda Yu、Chijimatsu Ryota、Vecchione Andrea、Arai Takahiro、Kitagawa Toru、Ofusa Ken、Yabumoto Masami、Hirotsu Takaaki、Eguchi Hidetoshi、Doki Yuichiro、Ishii Hideshi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 14 Pages: 7278-7278

    • DOI

      10.3390/ijms22147278

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 膵腫瘍アミノ酸代謝が関わるRNAプロセシング異常の解明と臨床応用2023

    • Author(s)
      孟 思昆、佐藤 広陸、佐々木 一樹、荒尾 泰子、斉藤 佳子、土岐 祐一郎、江口 英利、原 知明、石井 秀始
    • Organizer
      第9回 がんと代謝研究会 in 松山
    • Related Report
      2023 Annual Research Report
  • [Presentation] m6A により制御される PLK1 の細胞周期恒常性は膵癌において新規放射線治療の標的となる2022

    • Author(s)
      立川 章太郎、玉利 慶介、光藤 傑、秋田 裕史、小林 省吾、村雲 芳樹、土岐 祐一郎、江口 英利、小川 和彦、石井 秀始
    • Organizer
      第81回日本癌学会学術総会
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] miRNA 改変型核酸医薬品はマウス消化器がんモデルで腫瘍を効果的に抑制する2022

    • Author(s)
      佐藤 広陸、佐々木 一樹、荒尾 泰子 、竹田 佑、山田 大作 、富丸 慶人 、三吉 範克、高橋 秀典、小林 省吾 、森 正樹、土岐 祐一郎、江口 英利、石井 秀始
    • Organizer
      第81回日本癌学会学術総会
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] 膵癌のシングルセル RNA シークエンスデータセットの統合と再構築2022

    • Author(s)
      竹田 佑、千々松 良太、小林 省吾、北風 雅敏、山田 大作、高橋 秀典、森 正樹、土岐 祐一郎、江口 英利、石井 秀始
    • Organizer
      第81回日本癌学会学術総会
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] 転移と微小環境2021

    • Author(s)
      八代 正和、石井 秀始
    • Organizer
      第30回日本がん転移学会学術集会・総会
    • Related Report
      2021 Research-status Report
  • [Presentation] エピトランスクリプトームと腫瘍多様性2021

    • Author(s)
      石井 秀始、HaoJian Zhang
    • Organizer
      第80回日本癌学会学術総会
    • Related Report
      2021 Research-status Report
  • [Presentation] 早期膵がんのバイオマーカーとしての RNA 修飾2021

    • Author(s)
      今野 雅允、石井 秀始
    • Organizer
      第80回日本癌学会学術総会
    • Related Report
      2021 Research-status Report
  • [Presentation] One Carbon代謝に基づく消化器がんの精密なバイオマーカー研究の新展開2021

    • Author(s)
      松﨑 潤太郎、石井 秀始、安井 隆雄
    • Organizer
      第41回日本分子腫瘍マーカー研究会
    • Related Report
      2021 Research-status Report
  • [Presentation] 早期膵がんのスクリーニングに向けた線虫テスト2021

    • Author(s)
      浅井 歩、荒尾 泰子、千々松 良太、石井 秀始
    • Organizer
      第3回日本生物診断研究会
    • Related Report
      2021 Research-status Report

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Published: 2021-07-13   Modified: 2025-01-30  

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