Recognition of HER2 expression in hepatocellular carcinoma and its significance in postoperative tumor recurrence.
Cancer Med
; 8(3): 1269-1278, 2019 03.
Article
em En
| MEDLINE
| ID: mdl-30714677
ABSTRACT
BACKGROUND:
The 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.METHODS:
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-ß cocultured JM1 cells, HCC biology, including cell survival, proliferation, and epithelial-to-mesenchymal transition (EMT) phenotypes were evaluated.RESULTS:
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 ß-catenin and inhibition of SMAD3.CONCLUSION:
HER2 expression pattern is linked with tumor stage and overall survival; the transforming function of HER2 is found more relevant through ß-catenin and SMAD3. HER2-targeted treatment is recommended to suppress the HER2-mediated tumor growth during postoperative liver regeneration.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Expressão Gênica
/
Carcinoma Hepatocelular
/
Receptor ErbB-2
/
Neoplasias Hepáticas
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Cancer Med
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
China