ArticleCancer medicine2019
Recognition of HER2 expression in hepatocellular carcinoma and its significance in postoperative tumor recurrence.
Article in Cancer medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 55 citations in OpenAlex.
- Assessment of Circulating Tumor DNA for Early Detection of Hepatocellular Carcinoma in Alpha-Fetoprotein-Negative Patients With Cirrhotic Nodules.JGH open : an open access journal of gastroenterology and hepatology · 2026Article
- Three Noble Metal Nanoparticles Demonstrated Distinct Biological Interactions and Cell Death Pathways in Human Hepatocarcinoma Cell Lines.Nanotechnology, science and applications · 2026Article
- Exploiting the cardioprotective potential of metformin against cardiotoxic agents.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- ATF6 Alleviates Endothelial Inflammation Following Extended Hepatectomy Through Inhibition of TRIM10/NF-κB Signaling.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- The antineoplastic effects of nuciferine on hepatocellular carcinoma are associated with suppression of the HER2-AKT/ERK1/2 signaling pathway.Discover oncology · 2025Article
- Expression of EGFRvIII and its co‑expression with wild‑type EGFR, or putative cancer stem cell biomarkers CD44 or EpCAM are associated with poorer prognosis in patients with hepatocellular carcinoma.Oncology reports · 2024Article
- Microcystin-LR activates serine/threonine kinases and alters the phosphoproteome in human HepaRG cells.Toxicon : official journal of the International Society on Toxinology · 2024Article
- Mechanisms and therapeutic targets of ErbB family receptors in hepatocellular carcinoma: a narrative review.Translational cancer research · 2024Review
- Molecular Mechanisms in Tumorigenesis of Hepatocellular Carcinoma and in Target Treatments-An Overview.Biomolecules · 2024Review
- Article
- Liquid biopsy kinetics and detection of ERBB2 amplification/HER2-positivity in refractory hepatocellular carcinoma.The journal of liquid biopsy · 2023Article
- Prognostic Value of Erythroblastic Leukemia Viral Oncogene Homolog 2 and Neuregulin 4 in Hepatocellular Carcinoma.Cancers · 2023Article
- Article
- Review
- Afatinib combined with anti-PD1 enhances immunotherapy of hepatocellular carcinomaFrontiers in oncology · 2023Article
- Targeted protein degradation using the lysosomal pathway.RSC medicinal chemistry · 2022Review
- Emerging degrader technologies engaging lysosomal pathways.Chemical Society reviews · 2022Review
- Association of alpha-fetoprotein and metastasis for small hepatocellular carcinoma: A propensity-matched analysis.Scientific reports · 2022Article
- Network-Pharmacology-Based Study on Active Phytochemicals and Molecular Mechanism ofInternational journal of molecular sciences · 2022Article
- Improving the Therapeutic Efficacy of Sorafenib for Hepatocellular Carcinoma by Repurposing Disulfiram.Frontiers in oncology · 2022Article
Corrections and comments
- Erratum issuedCorrigendum.2021
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe ERBB2 oncogene hypothesis is challenged in hepatocellular carcinoma (HCC) with the conflicting evidences of human epidermal growth factor receptor 2 (HER2) overexpression. HER2 could be a new target as a treatment option for HCC as well as tumor recurrence after surgery. HER2 in HCC biology needs further explorations.
methodsClinical and mRNA data of HCC patients were obtained from TCGA HCC cohort, GSE89377 and GSE115018. Western Blotting and immunohistochemistry were employed to test expression of HER2, E-cadherin, and Vimentin. In HepG2, JM1, HER2-transfected McA cells, and TGF-β cocultured JM1 cells, HCC biology, including cell survival, proliferation, and epithelial-to-mesenchymal transition (EMT) phenotypes were evaluated.
resultsERBB2 mRNA amplification was found in HCC datasets, and its expression was downregulated in high grade HCC with a worse overall survival. HER2 overexpression was identified in H4IIE, HepG2, JM1 cells, and 82% (14/17) HCC samples, and tumor stage was correlated with expression of HER2, E-cadherin, and Vimentin (P < 0.05). Trastuzumab with the high concentrations suppressed proliferation of HER2-positive hepatoma cells (P < 0.05); in the coculture model to induce EMT of JM1 cells, HER2 expression increased with downregulated E-cadherin and upregulated Vimentin. Trastuzumab intravenous injection inhibited in vivo tumor size and metastases (P < 0.05). Signal analysis revealed that HER2 functioned through upregulation of β-catenin and inhibition of SMAD3.
conclusionHER2 expression pattern is linked with tumor stage and overall survival; the transforming function of HER2 is found more relevant through β-catenin and SMAD3. HER2-targeted treatment is recommended to suppress the HER2-mediated tumor growth during postoperative liver regeneration.
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