The Clinical and Prognostic Implications of Pluripotent Stem Cell Markers Expression and Their Correlation with the WNT signal pathway in Hepatocellular Carcinoma

Asian Pac J Cancer Prev. 2020 Oct 1;21(10):2961-2970. doi: 10.31557/APJCP.2020.21.10.2961.

Abstract

Objectives: This study aimed to investigate the expression of SOX2, SOX9, p53, and β-catenin in hepatocellular carcinoma (HCC) and their correlation with clinicopathological parameters of prognostic importance.

Materials and methods: Seventy-five patients were enrolled in this study. All patients had full clinical and follow-up data and available paraffin blocks. Immunohistochemical analysis was performed and correlated with clinicopathological factors and patient survival.

Results: We detected the positive expression of SOX2, SOX9, p53, and β-catenin in 76%, 50.7%, 50.7%, and 77.9% of HCC specimens respectively. All studied markers showed a significant increase in the expression in tumor tissue specimens compared to non-tumor tissue. Both SOX2 and SOX9 expressions were significantly associated with adverse prognostic factors in HCC. Significant positive correlations were found between SOX2 and SOX9 and both p53 and β-catenin expression (r= 0.528, 0.485 and; r = 0.253, 0.327, respectively; p < 0.0001 for both of them). Regarding survival, we found that HCC patients with positive SOX2 and SOX9 expressions had significantly shorter overall survival (p=0.0001, each). Additionally, larger tumor size, tumor grade, high stage, tumor multiplicity, presence of cirrhosis, tumor necrosis, high p53 expression, and positive β-catenin expression were independent predictors of worse survival. A multivariate Cox analysis revealed that tumor grade, stage, p53, and SOX2 expression were independent predictors of unfavorable prognosis in overall survival (p=0.0001, p=0.0001,p=0.033; and p=0.003, respectively).

Conclusions: Our findings might provide an insight into SOX2 and SOX9's role in HCC and suggest that SOX2 might be targeted for HCC therapy.

Keywords: HCC; SOX2; SOX9; p53; β-catenin.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology*
  • Carcinoma, Hepatocellular / surgery
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Liver Neoplasms / surgery
  • Male
  • Middle Aged
  • Pluripotent Stem Cells / metabolism*
  • Pluripotent Stem Cells / pathology
  • Prognosis
  • SOX9 Transcription Factor / metabolism*
  • SOXB1 Transcription Factors / metabolism*
  • Survival Rate
  • Tumor Suppressor Protein p53 / metabolism*
  • Wnt Signaling Pathway
  • beta Catenin / metabolism*

Substances

  • Biomarkers, Tumor
  • CTNNB1 protein, human
  • SOX2 protein, human
  • SOX9 Transcription Factor
  • SOX9 protein, human
  • SOXB1 Transcription Factors
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • beta Catenin