ArticleJournal of translational medicine2014
Viral expression and molecular profiling in liver tissue versus microdissected hepatocytes in hepatitis B virus-associated hepatocellular carcinoma.
Article in Journal of translational medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 2 of them syntheses that pooled it.
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Who cites it
51 citing papers in PubMed, 2 syntheses or guidelines pooled it, 72 citations in OpenAlex.
- The Neuroimmunome of Hepatitis Patients Associates With Disease Severity.Journal of medical virology · 2025Pooled it
- Mapping the knowledge domains of literature on hepatocellular carcinoma and liver failure: a bibliometric approach.Frontiers in oncology · 2025Pooled it
- Article
- The Intrinsic Innate Immunity of Hepatocytes Suppresses HBV Replication and Is Antagonized by HBx.Viruses · 2025Article
- Integrating bulk and single cell sequencing data to identify prognostic biomarkers and drug candidates in HBV associated hepatocellular carcinoma.Scientific reports · 2025Article
- Healthcare Disparities in the Treatment and Outcomes of Hepatocellular Carcinoma in South Africa.World journal of surgery · 2025Article
- TMPRSS2 as a Key Player in Viral Pathogenesis: Influenza and Coronaviruses.Biomolecules · 2025Review
- Machine Learning Approach and Bioinformatics Analysis Discovered Key Genomic Signatures for Hepatitis B Virus-Associated Hepatocyte Remodeling and Hepatocellular Carcinoma.Cancer informatics · 2025Review
- Identification of Two Distinct Immune Subtypes in Hepatitis B Virus (HBV)-Associated Hepatocellular Carcinoma (HCC).Cancers · 2024Article
- Construction and validation of a joint diagnosis model based on random forest and artificial intelligence network for hepatitis B-related hepatocellular carcinoma.Translational cancer research · 2024Article
- From metabolism to malignancy: the multifaceted role of PGC1α in cancer.Frontiers in oncology · 2024Review
- Exploring potential key genes and pathways associatedwith hepatocellular carcinoma prognosis through bioinformatics analysis, followed by experimental validation.American journal of translational research · 2024Article
- Exosome-Related FTCD Facilitates M1 Macrophage Polarization and Impacts the Prognosis of Hepatocellular Carcinoma.Biomolecules · 2023Article
- Identification of KNOP1 as a prognostic marker in hepatocellular carcinoma.Translational cancer research · 2023Article
- Integrated analysis of multiple transcriptomic data identifies ST8SIA6‑AS1 and LINC01093 as potential biomarkers in HBV‑associated liver cancer.Oncology letters · 2023Article
- NClinical and translational medicine · 2022Article
- Dissecting novel mechanisms of hepatitis B virus related hepatocellular carcinoma using meta-analysis of public data.World journal of gastrointestinal oncology · 2022Article
- Hepatitis B/D-Related Hepatocellular Carcinoma. A Clinical Literature Review.Journal of gastrointestinal cancer · 2021Review
- Absent in melanoma 1-like (AIM1L) serves as a novel candidate for overall survival in hepatocellular carcinoma.Bioengineered · 2021Article
- Role of chromosome 1q copy number variation in hepatocellular carcinoma.World journal of hepatology · 2021Review
Corrections and comments
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Authors and funding
17 authors at 7 institutions in 3 countries.
Funding
Abstract
backgroundThe molecular mechanisms whereby hepatitis B virus (HBV) induces hepatocellular carcinoma (HCC) remain elusive. We used genomic and molecular techniques to investigate host-virus interactions by studying multiple areas of the same liver from patients with HCC.
methodsWe compared the gene signature of whole liver tissue (WLT) versus laser capture-microdissected (LCM) hepatocytes along with the intrahepatic expression of HBV. Gene expression profiling was performed on up to 17 WLT specimens obtained at various distances from the tumor center from individual livers of 11 patients with HCC and on selected LCM samples. HBV markers in liver and serum were determined by real-time polymerase chain reaction (PCR) and confocal immunofluorescence.
resultsAnalysis of 5 areas of the liver showed a sharp change in gene expression between the immediate perilesional area and tumor periphery that correlated with a significant decrease in the intrahepatic expression of HB surface antigen (HBsAg). The tumor was characterized by a large preponderance of down-regulated genes, mostly involved in the metabolism of lipids and fatty acids, glucose, amino acids and drugs, with down-regulation of pathways involved in the activation of PXR/RXR and PPARα/RXRα nuclear receptors, comprising PGC-1α and FOXO1, two key regulators critically involved not only in the metabolic functions of the liver but also in the life cycle of HBV, acting as essential transcription factors for viral gene expression. These findings were confirmed by gene expression of microdissected hepatocytes. Moreover, LCM of malignant hepatocytes also revealed up-regulation of unique genes associated with cancer and signaling pathways, including two novel HCC-associated cancer testis antigen genes, NUF2 and TTK.
conclusionsIntegrated gene expression profiling of whole liver tissue with that of microdissected hepatocytes demonstrated that HBV-associated HCC is characterized by a metabolism switch-off and by a significant reduction in HBsAg. LCM proved to be a critical tool to validate gene signatures associated with HCC and to identify genes that may play a role in hepatocarcinogenesis, opening new perspectives for the discovery of novel diagnostic markers and therapeutic targets.
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