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Development of a novel liver cancer risk diagnostic method targeting circulating tumor cells

Research Project

Project/Area Number 21K15944
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 53010:Gastroenterology-related
Research InstitutionUniversity of Fukui

Principal Investigator

Ofuji Kazuya  福井大学, 学術研究院医学系部門, 特別研究員 (60597699)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords肝がん / 血中循環腫瘍細胞 / 肝細胞癌
Outline of Research at the Start

肝がんは治療後においても再発、転移が高率であり、再発予測と制御が重要な課題である。がん組織より血中に遊離する循環腫瘍細胞(CTC;circulating tumor cell) は新たな診断・予後予測のバイオマーカー候補である。本研究ではCTCの遺伝子発現解析による肝がんの進展・転移リスク予測評価法の構築を目的とする。CTC遺伝子発現群による新規肝がんリスク診断法を開発する。CTC解析による再発、転移リスク評価法開発は、再発、転移制御を目的とした個別化医療への応用、展開が期待される。

Outline of Final Research Achievements

In this study, we evaluated the quantitative and gene expression of circulating tumor cells in the blood of patients with hepatocellular carcinoma treated with atezolizumab-bevacizumab combination therapy.The number of CTCs in the PR/SD group decreased over the course of treatment and was significantly lower than that in the PD group.NGS analysis of CTC gene expression revealed changes in the expression of 99 genes related to cancer progression, including epithelial-mesenchymal transition, stemness, and proliferative potential, during the course of treatment, and hierarchical clustering analysis stratified the treatment effect into two clusters: PR/SD group and poor PD group.Pathway analysis showed that the expression of apoptosis-related signaling pathway genes in the PR/SD group and TGF-β signaling pathway-related genes in the PD group were significantly upregulated.

Academic Significance and Societal Importance of the Research Achievements

本研究課程においてAtezolizumab-Bevacizumab併用療法肝がん症例における血中循環腫瘍細胞の定量性、遺伝子発現について解析可能であった。その結果、治療経過に応じてCTC定量性の変動が確認された。また、CTC遺伝子発現解析により免疫療法奏効例においてアポトーシスシグナル経路が亢進している一方、TGF-βシグナル経路の活性化が免疫療法中の治療耐性において重要な役割を担っていることが示唆された。以上の結果より、肝癌複合免疫療法中におけるCTCはがん進展・治療耐性をきたすがん細胞プロファイルを明らかにする有用なバイオマーカーとなる可能性が示された。

Report

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

    (10 results)

All 2023 2022

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

  • [Journal Article] Histology and cytokine levels in hepatic injury accompanying a case of non-severe COVID-192023

    • Author(s)
      Matsuda Hidetaka、Nosaka Takuto、Hiramatsu Katsushi、Takahashi Kazuto、Naito Tatsushi、Ofuji Kazuya、Ohtani Masahiro、Imamura Yoshiaki、Iwasaki Hiromichi、Nakamoto Yasunari
    • Journal Title

      Clinical Journal of Gastroenterology

      Volume: 16 Issue: 2 Pages: 270-278

    • DOI

      10.1007/s12328-023-01755-4

    • Related Report
      2023 Annual Research Report 2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hepatocellular Carcinoma Progression Promoted by 5-Lipoxygenase Activity in CD163(+) Tumor-Associated Macrophages.2023

    • Author(s)
      Nosaka T, Murata Y, Takahashi K, Naito T, Ofuji K, Matsuda H, Ohtani M, Hiramatsu K, Imamura Y, Goi T, Nakamoto Y.
    • Journal Title

      Biomed Pharmacother.

      Volume: 162 Pages: 114592-114592

    • DOI

      10.1016/j.biopha.2023.114592

    • Related Report
      2023 Annual Research Report 2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Elderly onset congenital hepatic fibrosis with portal hypertension diagnosed after recurrent cholangitis: a case report2022

    • Author(s)
      Takahashi Kazuto、Ofuji Kazuya、Nosaka Takuto、Naito Tatsushi、Matsuda Hidetaka、Ohtani Masahiro、Hiramatsu Katsushi、Harada Kenichi、Naiki Hironobu、Nakamoto Yasunari
    • Journal Title

      Clinical Journal of Gastroenterology

      Volume: 15 Issue: 3 Pages: 611-616

    • DOI

      10.1007/s12328-022-01620-w

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Successful early diagnosis of monomorphic epitheliotropic intestinal T-cell lymphoma manifesting as chronic diarrhea and hypokalemia using video capsule endoscopy and double-balloon enteroscopy.2022

    • Author(s)
      Naito T, Nosaka T, Takahashi K, Ofuji K, Matsuda H, Ohtani M, Hiramatsu K, Imamura Y, Yamauchi T, Nakamoto Y.
    • Journal Title

      Clin J Gastroenterol.

      Volume: 15(5) Issue: 5 Pages: 913-919

    • DOI

      10.1007/s12328-022-01676-8

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] A rare case of eosinophilic gastritis induced by nivolumab therapy for metastatic melanoma.2022

    • Author(s)
      Tsuji A, Hiramatsu K, Namikawa S, Yamamoto A, Midori Y, Murata Y, Tanaka T, Nosaka T, Naito T, Takahashi K, Ofuji K, Matsuda H, Ohtani M, Imamura Y, Iino S, Hasegawa M, Nakamoto Y.
    • Journal Title

      Clin J Gastroenterol.

      Volume: 5(5) Issue: 5 Pages: 876-880

    • DOI

      10.1007/s12328-022-01680-y

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cholesterol crystal embolism in multiple organs after transarterial chemoembolization for hepatocellular carcinoma: An autopsy case report.2022

    • Author(s)
      Yamashita J, Nosaka T, Takahashi K, Naito T, Ofuji K, Matsuda H, Ohtani M, Hiramatsu K, Kobayashi M, Nakamoto Y.
    • Journal Title

      Medicine (Baltimore)

      Volume: 101(39) Issue: 39 Pages: e30769-e30769

    • DOI

      10.1097/md.0000000000030769

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Clinical Usefulness of Skeletal Muscle Quantity as Prognostic Factor in Elderly Patients with Advanced Pancreatic Cancer Receiving Nab-Paclitaxel Plus Gemcitabine Chemotherapy2022

    • Author(s)
      Akazawa Y, Ohtani M, Nosaka T, Takahashi K, Naito T, Ofuji K, Matsuda H, Hiramatsu K, Nakamoto Y
    • Organizer
      DDW 2022
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Risk Factors for Pancreatic Malignancies in Patients with Low-Risk Branch Duct Intraductal Papillary Mucinous Neoplasms after 5 Years of Long-Term Follow-Up2022

    • Author(s)
      Ohtani M, Ofuji K, Akazawa Y, Nosaka T, Takahashi K, Naito T, Matsuda H, Hiramatsu K, Nakamoto Y
    • Organizer
      DDW 2022
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Increased Liver Volume Measured using a 3d Medical Imaging in Patients with Advanced Decompensated Cirrhosis Treated with Balloon-Occluded Retrograde Transvenous Obliteration (B-Rto)2022

    • Author(s)
      Yamamoto A, Ofuji K, Nosaka T, Akazawa Y, Naito T, Takahashi K, Matsuda H, Ohtani M, Nakamoto Y
    • Organizer
      AASLD 2022
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Stem Cell Signature of Peripheral Circulating Tumor Cells correlated with therapeutic effects of Atezolizumab plus Bevacizumab in unresectable HCC patients2022

    • Author(s)
      Murata Y, Nosaka T, Takahashi K, Naito T, Ofuji K, Matsuda H, Ohtani M, Nakamoto Y
    • Organizer
      AASLD 2022
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research

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Published: 2021-04-28   Modified: 2025-01-30  

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