ArticleHepatology international2022
Analysis of viral integration reveals new insights of oncogenic mechanism in HBV-infected intrahepatic cholangiocarcinoma and combined hepatocellular-cholangiocarcinoma.
Article in Hepatology international, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 13 citations in OpenAlex.
- Combined hepatocellular-cholangiocarcinoma: a contemporary pathologic and molecular perspective.Journal of liver cancer · 2026Review
- From organelles to therapy: rethinking combined hepatocellular-cholangiocarcinoma.Frontiers in cell and developmental biology · 2026Review
- Long-Term Outcomes of Combined Hepatocellular Carcinoma-Cholangiocarcinoma After Liver Transplantation in Patients with or without Concurrent Hepatocellular Carcinoma.Annals of transplantation · 2025Article
- The clinical value of lymph-node dissection in hepatitis B virus-associated intrahepatic cholangiocarcinoma.Medicine · 2025Observational
- Chronic Liver Disease Associated Cholangiocarcinoma: Genomic Insights and Precision Therapeutic Strategies.Cancers · 2025Review
- Hepatitis B virus promotes liver cancer by modulating the immune response to environmental carcinogens.Nature communications · 2025Article
- Unveiling the dynamics and therapeutic potential of mInternational journal of biological sciences · 2025Review
- Rapid Detection ofBiomolecules · 2024Article
- The Dark Side of Human Hepatocyte Plasticity.Gastroenterology · 2024Article
- Review
- HBV Infection and Host Interactions: The Role in Viral Persistence and Oncogenesis.International journal of molecular sciences · 2023Review
- Genomic Analysis of Amphioxus Reveals a Wide Range of Fragments Homologous to Viral Sequences.Viruses · 2023Article
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundIntegration of HBV DNA into the human genome could progressively contribute to hepatocarcinogenesis. Both intrahepatic cholangiocarcinoma (ICC) and combined hepatocellular-cholangiocarcinoma (CHC) are known to be associated with HBV infection. However, the integration of HBV and mechanism of HBV-induced carcinogenesis in ICC and CHC remains unclear.
methods41 patients with ICC and 20 patients with CHC were recruited in the study. We conducted HIVID analysis on these 61 samples to identify HBV integration sites in both the tumor tissues and adjacent non-tumor liver tissues. To further explore the effect of HBV integration on gene alteration, we selected paired tumors and adjacent non-tumor liver tissues from 3 ICC and 4 CHC patients for RNA-seq and WGS.
resultsWe detected 493 HBV integration sites in ICC patients, of which 417 were from tumor samples and 76 were from non-tumor samples. And 246 HBV integration sites were detected in CHC patients, of which 156 were located in the genome of tumor samples and 90 were in non-tumor samples. Recurrent HBV integration events were detected in ICC including TERT, ZMAT4, MET, ANKFN1, PLXNB2, and in CHC like TERT, ALKBH5. Together with our established data of HBV-infected hepatocellular carcinoma, we found that HBV preferentially integrates into the specific regions which may affect the gene expression and regulation in cells and involved in carcinogenesis. We further performed genomic and transcriptomic sequencing of three ICC and four CHC patients, and found that HBV fragments could integrate near some important oncogene like TERT, causing large-scale genome variations on nearby genomic sequences, and at the same time changing the expression level of the oncogenes.
conclusionComparative analysis demonstrates numerous newly discovered mutational events in ICC and CHC resulting from HBV insertions in the host genome. Our study provides an in-depth biological and clinical insights into HBV-induced ICC and CHC.
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