Integrated analysis involving spatial transcriptomics and single-cell transcriptomics to elucidate the mechanism of hepatitis C-derived hepatocellular carcinogenesis.

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K20810
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0901:Oncology and related fields
• Research Institution: Wakayama Medical University
• Principal Investigator: Imafuku Tadashi 和歌山県立医科大学, 先端医学研究所, 助教 (10908809)
• Project Period (FY): 2021-08-30 – 2023-03-31
• Keywords: 空間トランスクリプトミクス / 腫瘍微小環境 / C型肝炎由来肝癌 / 細胞間相互作用

Outline of Final Research Achievements

Hepatocellular carcinogenesis after hepatitis C virus elimination is still common. Cellular heterogeneity in tumor tissues makes it difficult to elucidate the mechanism of cancer pathology. Single-cell transcriptomics is a powerful tool for analyzing cellular heterogeneity, but it lacks spatial information such as the localization of cells. Recent reports have shown that spatial transcriptomics can conduct transcriptomics on intact tissue to preserve spatial information. In this study, we aimed to elucidate the mechanism of cancer pathology by spatial transcriptomics and single-cell transcriptomics. This integrated analysis revealed that the genes to exacerbate cancer were highly expressed in hepatocarcinoma cells adjacent to cells in stroma area. In addition, we also identified the hepatocyte highly expressing the genes to exacerbate cancer and its marker genes. Hence, we found one aspect of the mechanism of hepatitis C-derived carcinogenesis and cancer progression.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

本研究では、C型肝炎ウイルス排除後に発がんした肝臓癌組織のがん領域と正常領域の境界部に対して空間トランスクリプトーム解析を試行し、がん細胞と間質領域の細胞が隣接する領域に着目して解析することで、病態進展に関連する候補遺伝子及び前癌肝実質細胞とそのマーカー遺伝子を見出した。従って、この相互作用を阻害することで、C型肝炎からの発癌や進展を抑制できる可能性があり、新規治療法の開発に繋がると考える。