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

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K15944
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: University 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
• Keywords: 肝がん / 血中循環腫瘍細胞

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．

Free Research Field

Oncology

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。