Multiple Roles for Hepatitis B and C Viruses and the Host in the Development of Hepatocellular Carcinoma

Wangensteen, Kirk J.; Chang, Kyong–Mi

doi:10.1002/hep.31481

Cited by 33 publications

(29 citation statements)

References 106 publications

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“…3 , 4 In more than 90% of cases, HCC occurs on a background of cirrhosis, whereas in a minority of cases, particularly with HBV infection and increasingly with NASH, it develops in livers with minimal or no fibrosis. 5 , 6 Patients with cirrhosis have annual incidence rates of HCC of 2-4%. 7 Other risk factors include toxins, autoimmune hepatitis, cholestatic liver diseases, hereditary haemochromatosis, and α1-antitrypsin deficiency.…”

Section: Introductionmentioning

confidence: 99%

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Cellular origins of regenerating liver and hepatocellular carcinoma

2022

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Section: Introductionmentioning

confidence: 99%

“… 8 A family history of HCC is an independent risk factor for HCC, and cancer-associated genetic variants can be detected in the germline of patients with HCC, but the full spectrum of underlying genetic risk factors is not yet known. 6 , 9…”

Section: Introductionmentioning

confidence: 99%

Cellular origins of regenerating liver and hepatocellular carcinoma

2022

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“…1 The development of HCC is strongly linked to underlying chronic liver disease and cirrhosis, most commonly because of chronic infection with either hepatitis C virus (HCV) or hepatitis B virus (HBV). 2 Other HCC risk factors include nonalcoholic fatty liver disease; excessive alcohol use; exposure to hepatotoxins; and rare genetic disorders such as hereditary hemochromatosis, hereditary tyrosinemia, and acute hepatic porphyrias. 1,3 Analyses of HCC tumor tissues have revealed an array of somatic mutations, the most common being TERT promoter-activating mutations, CTNNB1-activating mutations, and TP53-inactivating mutations.…”

Section: Introductionmentioning

confidence: 99%

“…1,3 Analyses of HCC tumor tissues have revealed an array of somatic mutations, the most common being TERT promoter-activating mutations, CTNNB1-activating mutations, and TP53-inactivating mutations. 2 HCC has not been linked with pathogenic and likely pathogenic (P/LP) variants in germline cancer predisposition genes to date.…”

Section: Introductionmentioning

confidence: 99%

Multigene Panel Testing in Individuals With Hepatocellular Carcinoma Identifies Pathogenic Germline Variants

Mezina

Philips

Bogus

et al. 2021

JCO Precision Oncology

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PURPOSE Hepatocellular carcinoma (HCC) has well-defined environmental risk factors. In addition, epidemiologic studies have suggested hereditary risk factors. The goals of this study were to determine the rate of pathogenic and likely pathogenic (P/LP) germline variants in cancer predisposition genes in patients with HCC, possible enrichment of P/LP variants in particular genes, and potential impact on clinical management. MATERIALS AND METHODS A prospective study at a tertiary medical center enrolled 217 patients with a personal history of HCC. Multigene panel testing was performed for 134 cancer predisposition genes in all patients. The rate of P/LP variants was compared with population rates. A separate retrospective cohort included 219 patients with HCC who underwent testing at a commercial laboratory. RESULTS In the prospective cohort, P/LP germline variants were identified in 25 of 217 patients with HCC (11.5%). Four patients (1.8%) had P/LP variants in the highly penetrant cancer genes BRCA2 (n = 2), MSH6 (n = 1), and PMS2 (n = 1). In addition, multiple patients had P/LP variants in FANCA (n = 5) and BRIP1 (n = 4), which were significantly enriched in HCC compared with the general population. Detection of P/LP variants led to changes in clinical management in regard to therapy selection, screening recommendations, and cascade testing of relatives. In a separate retrospective analysis of 219 patients with HCC, 30 (13.7%) were positive for P/LP variants including 13 (5.9%) with highly penetrant genes APC (n = 2), BRCA1 (n = 1), BRCA2 (n = 6), MSH2 (n = 2), or TP53 (n = 2). CONCLUSION P/LP germline variants in cancer predisposition genes were detected in 11%-14% of patients with HCC. Inherited genetics should not be overlooked in HCC as there are important implications for precision treatment, future risk of cancers, and familial cancer risk.

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“…Although the causes of HCC are complex, the most common is hepatitis virus infection, including hepatitis B (HBV) and hepatitis C (HCV). Longterm chronic viral infection can lead to hepatitis cirrhosis, which eventually develops into HCC (21). Various studies have found that abnormal methylation plays an important regulatory role in the occurrence and development of HCC caused by viral hepatitis and could be an independent risk factor for HCC recurrence (22).…”

Section: Discussionmentioning

confidence: 99%

Combined screening analysis of aberrantly methylated-differentially expressed genes and pathways in hepatocellular carcinoma

Cao¹,

Zhang²,

Zhang³

et al. 2022

J Gastrointest Oncol

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Background: Methylation plays an important role in hepatocellular carcinoma (HCC) by altering the expression of key genes. The aim of this study was to screen the aberrantly methylated-differentially expressed genes (DEGs) in HCC and elucidate their underlying molecular mechanism.Methods: Gene expression microarrays (GSE101685) and gene methylation microarrays (GSE44909) were selected. DEGs and differentially methylated genes (DMGs) were screened. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using the Database for Annotation, Visualization, and Integrated discovery (DAVID). The Search Tool for the Retrieval of Interacting Genes (STRING) database was used to analyze the functional protein-protein interaction (PPI) network. Molecular Complex Detection (MCODE) analysis was performed using the Cytoscape software. Hub genes were verified in The Cancer Genome Atlas (TCGA) database.Results: A total of 80 hypomethylation-high expression genes (Hypo-HGs) were identified. Pathway enrichment analysis showed DNA replication, cell cycle, viral carcinogenesis, and the spliceosome. The top 5 hub genes were minichromosome maintenance complex component 3 (MCM3), checkpoint kinase 1 (CHEK1), kinesin family member 11 (KIF11), PDZ binding kinase (PBK), and Rac GTPase activating protein 1 (RACGAP1). In addition, 189 hypermethylation-low expression genes (Hyper-LGs) were identified. Pathway enrichment analysis indicated enrichment in metabolic pathways, drug metabolismother enzymes, and chemical carcinogenesis. The top 5 hub genes were leukocyte immunoglobulin like receptor B2 (LILRB2), formyl peptide receptor 1 (FPR1), S100 calcium binding protein A9 (S100A9), S100 calcium binding protein A8 (S100A8), and myeloid cell nuclear differentiation antigen (MNDA). The methylation status and mRNA expression of MCM3, CHEK1, KIF11, PBK, and S100A9 were consistent in the TCGA database and significantly correlated with the prognosis of patients.Conclusions: Combined screening of aberrantly methylated-DEGs based on bioinformatic analysis may provide new clues for elucidating the epigenetic mechanism in HCC. Hub genes, including MCM3, CHEK1, KIF11, PBK, and S100A9, may serve as biomarkers for the precise diagnosis of HCC.

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Multiple Roles for Hepatitis B and C Viruses and the Host in the Development of Hepatocellular Carcinoma

Cited by 33 publications

References 106 publications

Cellular origins of regenerating liver and hepatocellular carcinoma

Cellular origins of regenerating liver and hepatocellular carcinoma

Multigene Panel Testing in Individuals With Hepatocellular Carcinoma Identifies Pathogenic Germline Variants

Combined screening analysis of aberrantly methylated-differentially expressed genes and pathways in hepatocellular carcinoma

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