• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Identification of biomarker in intrahepatic recurrence of hepatocellular carcinoma through extracellular vesicles

Research Project

Project/Area Number 19K09146
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 55020:Digestive surgery-related
Research InstitutionOsaka University

Principal Investigator

Noda Takehiro  大阪大学, 医学系研究科, 助教 (50528594)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords肝細胞癌 / microRNA / 予後 / 手術 / リキッドバイオプシー / 前転移ニッチ / 腫瘍血管内皮細胞 / 腫瘍血管正常化 / 疲弊化 / PFKFB3 / GPNMB / 肝内転移 / エクソソーム / miR / miRNA / 肝癌 / 転移
Outline of Research at the Start

肝細胞癌患者の5年生存率は約40%と、その治療成績は依然として不良である。その原因として, 治療後に高率に肝内転移を来すことが挙げられるが、転移成立の分子メカニズムについては不明な点が多い。エクソソームは細胞間伝達物質としての機能を有し、エクソソームを介した前転移ニッチ形成が肝内転移成立に関与していると考えられている。本研究では, 当科にて樹立した新規肝細胞癌高転移能株を用いて、腫瘍細胞由来エクソソームを介した前転移ニッチ形成機構の解明と、その中心的役割を果たすmiRNAの同定・機能解析により肝細胞癌患者の予後を改善することを目的とする。

Outline of Final Research Achievements

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death. Recently, exosomal microRNAs(miRNAs) have been reported to have a role in the formation of the pre-metastatic niche and as promising biomarkers in patients with malignancy. Here we aimed to clarify the molecular mechanisms of intrahepatic metastasis and to identify a novel biomarker miRNA in patients with HCC. The miRNAs (miR-638, miR-663a, miR-3648, and miR-4258) could attenuate
endothelial junction integrity by inhibiting VE-cadherin and ZO-1 expression. In patients with HCC, higher serum exosomal miR-638 expression was associated with
tumor recurrence. In conclusion, the miRNAs secreted from a highly metastatic cancercell can promote vascular permeability via downregulation of endothelial expressionof VE-cadherin and ZO-1. Serum exosomal miR-638 expression holds potential for serving as a significant and independent prognostic marker in HCC.

Academic Significance and Societal Importance of the Research Achievements

リキッドバイオプシーのリソースとしてエクソソームが着目され、様々な研究が行われている。エクソソームの膜タンパクやmiRNAに着目したバイオマーカーの報告があり、いずれにおいても早期診断や術後フォローに応用できる可能性が報告されている。本研究で同定したmiR-638については、肝細胞癌術前の高発現が再発予測マーカーとして応用できる可能性が考えられた。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (13 results)

All 2022 2021 2020

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Open Access: 4 results) Presentation (6 results)

  • [Journal Article] Tumor endothelial cell-induced CD8 + T-cell exhaustion via GPNMB in hepatocellular carcinoma2022

    • Author(s)
      Sakano Yoshihiro、Noda Takehiro、Kobayashi Shogo、Sasaki Kazuki、Iwagami Yoshifumi、Yamada Daisaku、Tomimaru Yoshito、Akita Hirofumi、Gotoh Kunihito、Takahashi Hidenori、Asaoka Tadafumi、Tanemura Masahiro、Wada Hisashi、Doki Yuichiro、Eguchi Hidetoshi
    • Journal Title

      Cancer Science

      Volume: - Issue: 5 Pages: 1625-1638

    • DOI

      10.1111/cas.15331

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Serum exosomal miR‐638 is a prognostic marker of HCC via downregulation of VE‐cadherin and ZO‐1 of endothelial cells2021

    • Author(s)
      Yokota Y, Noda T, Okumura Y, Kobayashi S, Iwagami Y, Yamada D, Tomimaru Y, Akita H, Gotoh K, Takeda Y, Tanemura M, Murakami T, Umeshita K, Doki Y, Eguchi H.
    • Journal Title

      Cancer Science

      Volume: 112 Issue: 3 Pages: 1275-1288

    • DOI

      10.1111/cas.14807

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical Significance of Acylphosphatase 1 Expression in Combined HCC-iCCA, HCC, and iCCA2021

    • Author(s)
      Yoshihiro Sakano, Takehiro Noda, Shogo Kobayashi, Akihiro Kitagawa, Yoshifumi Iwagami, Daisaku Yamada, Yoshito Tomimaru, Hirofumi Akita, Kunihito Gotoh, Tadafumi Asaoka, Masahiro Tanemura, Koji Umeshita, Koshi Mimori, Yuichiro Doki, Hidetoshi Eguchi
    • Journal Title

      Dig Dis Sci .

      Volume: -

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of c-MET reverses radiation-induced malignant potential in pancreatic cancer2021

    • Author(s)
      Mori Soichiro、Akita Hirofumi、Kobayashi Shogo、Iwagami Yoshifumi、Yamada Daisaku、Tomimaru Yoshito、Noda Takehiro、Gotoh Kunihito、Takeda Yutaka、Tanemura Masahiro、Doki Yuichiro、Eguchi Hidetoshi
    • Journal Title

      Cancer Letters

      Volume: 512 Pages: 51-59

    • DOI

      10.1016/j.canlet.2021.04.029

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of glycolytic activator PFKFB3 suppresses tumor growth and induces tumor vessel normalization in hepatocellular carcinoma2021

    • Author(s)
      Matsumoto Kenichi、Noda Takehiro、Kobayashi Shogo、Sakano Yoshihiro、Yokota Yuki、Iwagami Yoshifumi、Yamada Daisaku、Tomimaru Yoshito、Akita Hirofumi、Gotoh Kunihito、Takeda Yutaka、Tanemura Masahiro、Umeshita Koji、Doki Yuichiro、Eguchi Hidetoshi
    • Journal Title

      Cancer Letters

      Volume: 500 Pages: 29-40

    • DOI

      10.1016/j.canlet.2020.12.011

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A case report of hepatocellular carcinoma derived from Rastelli procedure-related congestive liver disease2021

    • Author(s)
      Sakano Yoshihiro、Noda Takehiro、Kobayashi Shogo、Iwagami Yoshifumi、Yamada Daisaku、Tomimaru Yoshito、Gotoh Kunihito、Umeshita Koji、Doki Yuichiro、Eguchi Hidetoshi
    • Journal Title

      Clinical Journal of Gastroenterology

      Volume: 14 Issue: 5 Pages: 1525-1529

    • DOI

      10.1007/s12328-021-01488-2

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The blockade of interleukin‐33 released by hepatectomy would be a promising treatment option for cholangiocarcinoma2020

    • Author(s)
      Nagaoka Satoshi、Yamada Daisaku、Eguchi Hidetoshi、Yokota Yuki、Iwagami Yoshifumi、Asaoka Tadafumi、Noda Takehiro、Kawamoto Koichi、Gotoh Kunihito、Kobayashi Shogo、Miyoshi Eiji、Doki Yuichiro、Mori Masaki
    • Journal Title

      Cancer Science

      Volume: 112 Issue: 1 Pages: 347-358

    • DOI

      10.1111/cas.14709

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 肝細胞癌転移機序における血管内皮細胞が果たす役割2021

    • Author(s)
      野田剛広、小林省吾、横田祐貴、阪野佳弘、岩上佳史、山田大作、富丸慶人、秋田裕史、後藤邦仁、土岐祐一郎、江口英利
    • Organizer
      第30回 日本癌転移学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 肝細胞癌における血管内皮細胞を標的とした転移機序解明と治療応用の可能性2021

    • Author(s)
      野田剛広、小林省吾、横田祐貴、阪野佳弘、岩上佳史、山田大作、富丸慶人、秋田裕史、後藤邦仁、土岐祐一郎、江口英利
    • Organizer
      第19回 日本消化器外科学会大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 混合型肝癌におけるACYP1発現の意義の検討2021

    • Author(s)
      阪野佳弘、野田剛広、小林省吾、岩上佳史、山田大作、富丸慶人、秋田裕史、後藤邦仁、土岐祐一郎、江口英利
    • Organizer
      第121回日本外科学会定期学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] マウス肝細胞癌における腫瘍血管内皮細胞と通常血管内皮細胞の比較2021

    • Author(s)
      阪野佳弘、野田剛広、小林省吾、岩上佳史、山田 大作、 富丸慶人、秋田裕史、後藤邦仁、土岐祐一郎、江口英利
    • Organizer
      第76回日本消化器外科学会総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 肝細胞癌転移モデルにおける肝内転移機序の解明2020

    • Author(s)
      横田祐貴、野田剛広、江口英利、奥村雄一郎、岩上佳史、富丸慶人、秋田裕史、後藤邦仁、小林省吾、森正樹、土岐祐一郎
    • Organizer
      第120回日本外科学会定期学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] Extracellular vesicles from HCC, implication for metastatic mechanism and prognostic indicator2020

    • Author(s)
      横田祐貴、野田剛広、江口英利、奥村雄一郎、岩上佳史、富丸慶人、秋田裕史、後藤邦仁、小林省吾、森正樹、土岐祐一郎
    • Organizer
      第79回日本癌学会学術集会
    • Related Report
      2020 Research-status Report

URL: 

Published: 2019-04-18   Modified: 2023-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi