Expression and prognostic value of HER-2/neu, STAT3 and SOCS3 in hepatocellular carcinoma

Clin Res Hepatol Gastroenterol. 2019 Jun;43(3):282-291. doi: 10.1016/j.clinre.2018.09.011. Epub 2018 Oct 29.

Abstract

Background and aims: Hepatocellular carcinoma (HCC) is a complex and heterogeneous tumor with several genomic alterations, while the viral-chemical etiology along with molecular mechanisms of HCC pathogenesis remains largely unknown. This study aimed to determine expression profile and prognostic value of HER-2/neu, STAT3 and SOCS3 in HCC.

Methods: Immunohistochemistry and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were performed to evaluate the expression of HER-2/neu, STAT3 and SOCS3 in HCC tissues and adjacent normal tissues collected from 176 HCC patients.

Results: HER-2/neu and STAT3 levels were higher and SOCS3 expression was lower in HCC tissues than in adjacent normal tissues. HER-2/neu, STAT3 and SOCS3 levels were associated with histological grade, tumor diameter, TNM stage, vascular invasion, lymph node metastasis and distant metastasis in HCC. SOCS3 expression was negatively associated with HER-2/neu and STAT3 expression. HCC patients with higher HER-2/neu and STAT3 levels had shorter overall, disease-free and disease-specific survival, whereas the opposite was found in patients with higher SOCS3 expression. In Cox regression analysis, tumor size, TNM stage, and STAT3 expression were identified as independent prognostic factors of HCC.

Conclusion: Taken together, these observations suggest that HER-2/neu, STAT3 and, SOCS3 are related to the aggressive tumor behavior and STAT3 has potential value as a prognostic factor for HCC.

Keywords: Human epidermal growth factor receptor-2; Primary hepatocellular carcinoma; Prognosis; Signal transducer and activator of transcription 3; Suppressor of cytokine signaling 3.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / mortality
  • Down-Regulation
  • Female
  • Humans
  • Immunohistochemistry
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / mortality
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Prognosis
  • Receptor, ErbB-2 / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • STAT3 Transcription Factor / metabolism*
  • Suppressor of Cytokine Signaling 3 Protein / metabolism*

Substances

  • Biomarkers, Tumor
  • SOCS3 protein, human
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Suppressor of Cytokine Signaling 3 Protein
  • ERBB2 protein, human
  • Receptor, ErbB-2