ArticleHepatology (Baltimore, Md.)2013
Sex bias occurrence of hepatocellular carcinoma in Poly7 molecular subclass is associated with EGFR.
Article in Hepatology (Baltimore, Md.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 59 citations in OpenAlex.
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- ZBTB20 regulates WNT/CTNNB1 signalling pathway by suppressing PPARG during hepatocellular carcinoma tumourigenesis.JHEP reports : innovation in hepatology · 2021Article
- Promoterless Transposon Mutagenesis Drives Solid Cancers via Tumor Suppressor Inactivation.Cancers · 2021Article
- APOBEC3A catalyzes mutation and drives carcinogenesis in vivo.The Journal of experimental medicine · 2020Article
- Transposon Insertion Mutagenesis in Mice for Modeling Human Cancers: Critical Insights Gained and New Opportunities.International journal of molecular sciences · 2020Review
- Relevance of EGFR Between Serum VEGF and MMP-9 in Primary Hepatocellular Carcinoma Patients with Transarterial Chemoembolization.OncoTargets and therapy · 2020Article
- HBx-K130M/V131I Promotes Liver Cancer in Transgenic Mice via AKT/FOXO1 Signaling Pathway and Arachidonic Acid Metabolism.Molecular cancer research : MCR · 2019Article
- A simplified transposon mutagenesis method to perform phenotypic forward genetic screens in cultured cells.BMC genomics · 2019Article
- Liver Cancer Gene Discovery Using Gene Targeting, Sleeping Beauty, and CRISPR/Cas9.Seminars in liver disease · 2019Review
- Sleeping Beauty Mouse Models of Cancer: Microenvironmental Influences on Cancer Genetics.Frontiers in oncology · 2019Review
- Co-sequencing and novel delayed anti-correlation identify function for pancreatic enriched microRNA biomarkers in a rat model of acute pancreatic injury.BMC genomics · 2018Article
- Chronic liver injury alters driver mutation profiles in hepatocellular carcinoma in mice.Hepatology (Baltimore, Md.) · 2018Article
- Article
- Transposons As Tools for Functional Genomics in Vertebrate Models.Trends in genetics : TIG · 2017Review
- Immunohistochemistry panel segregates molecular types of hepatocellular carcinoma in Brazilian autopsy cases.World journal of gastroenterology · 2016Article
- EGFR Signaling in Liver Diseases.International journal of molecular sciences · 2015Review
- Transposon mouse models to elucidate the genetic mechanisms of hepatitis B viral induced hepatocellular carcinoma.World journal of gastroenterology · 2015Review
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Authors and funding
17 authors at 4 institutions in 3 countries.
Funding
Abstract
unlabelledHepatocellular carcinoma (HCC) is one of the deadliest solid cancers and is the third leading cause of cancer-related death. There is a universal estimated male/female ratio of 2.5, but the reason for this is not well understood. The Sleeping Beauty (SB) transposon system was used to elucidate candidate oncogenic drivers of HCC in a forward genetics screening approach. Sex bias occurrence was conserved in our model, with male experimental mice developing liver tumors at reduced latency and higher tumor penetrance. In parallel, we explored sex differences regarding genomic aberrations in 235 HCC patients. Liver cancer candidate genes were identified from both sexes and genotypes. Interestingly, transposon insertions in the epidermal growth factor receptor (Egfr) gene were common in SB-induced liver tumors from male mice (10/10, 100%) but infrequent in female mice (2/9, 22%). Human single-nucleotide polymorphism data confirmed that polysomy of chromosome 7, locus of EGFR, was more frequent in males (26/62, 41%) than females (2/27, 7%) (P = 0.001). Gene expression-based Poly7 subclass patients were predominantly male (9/9) compared with 67% males (55/82) in other HCC subclasses (P = 0.02), and this subclass was accompanied by EGFR overexpression (P < 0.001).
conclusionSex bias occurrence of HCC associated with EGFR was confirmed in experimental animals using the SB transposon system in a reverse genetic approach. This study provides evidence for the role of EGFR in sex bias occurrences of liver cancer and as the driver mutational gene in the Poly7 molecular subclass of human HCC.
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