The analysis of oncogenesis induced by the integration of HBV genome in HBc positive non-B non-C hepatocellular carcinoma

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K22951
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0905:Surgery of the organs maintaining homeostasis and related fields
• Research Institution: Hokkaido University
• Principal Investigator: Suzuki Rigel 北海道大学, 医学研究院, 助教 (60870532)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: HBV / インテグレーション

Outline of Final Research Achievements

Recently, it has been revealed that some patients with non-B non-C hepatocellular carcinoma are positive for HBc antibody, a marker of pre-existing HBV infection. Although this indicates that there is a relationship between pre-existing HBV infection and the development of hepatocarcinogenesis, how HBV pre-existing infection causes hepatocarcinogenesis has remained unclear. Therefore, we attempted next-generation sequencing analysis to investigate the effect of HBV genome insertion on carcinogenesis using HBc positive non-B non-C hepatocellular carcinoma. Although next-generation sequencing analysis could not be performed due to the effect of the SARS-CoV-2, we examined the effect of deletion of the HBV genome insertion site, which had already been reported in cultured cells, to clarify that the HBV genome insertion is involved in tumorigenesis. The results showed that the insertion of the HBV genome is involved in tumorigenesis.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

本研究でHBVゲノムが挿入された培養細胞を用いて、CRISPR-Cas9システムでHBVのインテグレーション箇所を欠損させた場合、腫瘍形成が抑制されることを見出した。この結果と今後、HBc抗体陽性非ウイルス性肝癌のHBVゲノム挿入箇所を同定し、その変異の入ったマウスモデルを作製し、実際に同定した配列を標的とするCRISPR-Cas9システムで腫瘍形成が抑制された場合、これまで問題になっていたHBc抗体陽性非ウイルス性肝癌の新たな治療方法になる可能性がある。