ArticlePloS one2012
Re-evaluation of the carcinogenic significance of hepatitis B virus integration in hepatocarcinogenesis.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
42 citing papers in PubMed, 74 citations in OpenAlex.
- Multiplex gene editing suppresses random integration of hepatitis B virus DNA in chronically infected liver.Molecular therapy. Nucleic acids · 2026Article
- Tumor Cell-Derived CXCL2 Potentiates Neutrophil-Mediated Antitumor Immunity by Inhibiting Cholesterol Biosynthesis in Hepatocellular Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- HBV-encoded circRNA-5 promotes hepatocellular carcinoma progression by regulating the miR-9-3p/Hippo signaling axis.Microbiology spectrum · 2025Article
- Genome integration of human DNA oncoviruses.Journal of virology · 2025Review
- [Exploring the reasons for liver cancer occurrence still after long-term nucleos(t)ide analogue therapy in patients with chronic hepatitis B].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2024Review
- [Research progress on the effect of hepatitis B virus DNA integration on antiviral therapy].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2024Review
- HBV DNA Integration into Telomerase or MLL4 Genes and TERT Promoter Point Mutation as Three Independent Signatures in Subgrouping HBV-Related HCC with Distinct Features.Liver cancer · 2024Article
- HBV Infection and Host Interactions: The Role in Viral Persistence and Oncogenesis.International journal of molecular sciences · 2023Review
- COP1 Acts as a Ubiquitin Ligase for PCDH9 Ubiquitination and Degradation in Human Glioma.Molecular neurobiology · 2022Article
- Hepatitis B Virus Integration into Transcriptionally Active Loci and HBV-Associated Hepatocellular Carcinoma.Microorganisms · 2022Article
- Hepatitis B Virus DNA Integration, Chronic Infections and Hepatocellular Carcinoma.Microorganisms · 2021Review
- HBV Integration Induces Complex Interactions between Host and Viral Genomic Functions at the Insertion Site.Journal of clinical and translational hepatology · 2021Review
- Article
- NFATc3 inhibits hepatocarcinogenesis and HBV replication via positively regulating RIG-I-mediated interferon transcription.Oncoimmunology · 2021Article
- Pacbio Sequencing of PLC/PRF/5 Cell Line and Clearance of HBV Integration Through CRISPR/Cas-9 System.Frontiers in molecular biosciences · 2021Article
- Yin-Yang 1 and HBx protein activate HBV transcription by mediating the spatial interaction of cccDNA minichromosome with cellular chromosome 19p13.11.Emerging microbes & infections · 2020Article
- Hypomethylation in HBV integration regions aids non-invasive surveillance to hepatocellular carcinoma by low-pass genome-wide bisulfite sequencing.BMC medicine · 2020Article
- HBV DNA integrates into upregulated ZBTB20 in patients with hepatocellular carcinoma.Molecular medicine reports · 2020Article
- Serum HBV pregenomic RNA is correlated with Th1/Th2 immunity in treatment-naïve chronic hepatitis B patients.Journal of medical virology · 2020Article
- Comprehensive analysis of transcriptome profiles in hepatocellular carcinoma.Journal of translational medicine · 2019Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To examine the role of hepatitis B virus (HBV) integration in hepatocarcinogenesis, a systematic comparative study of both tumor and their corresponding non-tumor derived tissue has been conducted in a cohort of 60 HBV associated hepatocellular carcinoma (HCC) patients. By using Alu-polymerase chain reaction (PCR) and ligation-mediated PCR, 233 viral-host junctions mapped across all human chromosomes at random, no difference between tumor and non-tumor tissue was observed, with the exception of fragile sites (P = 0.0070). HBV insertions in close proximity to cancer related genes such as hTERT were found in this study, however overall they were rare events. No direct correlation between chromosome aberrations and the number of HBV integration events was found using a sensitive array-based comparative genomic hybridization (aCGH) assay. However, a positive correlation was observed between the status of several tumor suppressor genes (TP53, RB1, CDNK2A and TP73) and the number of chromosome aberrations (r = 0.6625, P = 0.0003). Examination of the viral genome revealed that 43% of inserts were in the preC/C region and 57% were in the HBV X gene. Strikingly, approximately 24% of the integrations examined had a breakpoint in a short 15 nt viral genome region (1820-1834 nt). As a consequence, all of the confirmed X gene insertions were C-terminal truncated, losing their growth-suppressive domain. However, the same pattern of X gene C-terminal truncation was found in both tumor and non-tumor derived samples. Furthermore, the integrated viral sequences in both groups had a similar low frequency of C1653T, T1753V and A1762T/G1764A mutations. The frequency and patterns of HBV insertions were similar between tumor and their adjacent non-tumor samples indicating that the majority of HBV DNA integration events are not associated with hepatocarcinogenesis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.