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pmid:30714677
Recognition of HER2 expression in hepatocellular carcinoma and its significance in postoperative tumor recurrence.
Ji-Hua Shi · Wen-Zhi Guo · Yang Jin · Hua-Peng Zhang · Chun Pang · Jie Li · Pål-Dag Line · Shui-Jun Zhang
Cancer medicine · 2019 doi:10.1002/cam4.2006
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Experiment
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Analysis
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Complete file
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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.\nMETHODS: Clinical 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.\nRESULTS: ERBB2 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.\nCONCLUSION: HER2 expression pattern is linked with tumor stage and overall survival; the transforming function of HER2 is found more relevant through β-catenin and SMAD3. 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