Clinical significance of hypoxia-inducible factor 1α, and its correlation with p53 and vascular endothelial growth factor expression in resectable esophageal squamous cell carcinoma

J Cancer Res Ther. 2020;16(2):269-275. doi: 10.4103/jcrt.JCRT_781_19.

Abstract

Background: Hypoxia-inducible factor 1α (HIF-1α), p53, and vascular endothelial growth factor (VEGF) are important factors that facilitate tumor progression. The aims of our study were to investigate the expression of HIF-1α, p53, and VEGF in esophageal squamous cell carcinoma (ESCC) treated by curative surgery and to analyze their association with clinicopathological parameters and clinical outcome.

Materials and methods: The surgical specimens from 120 patients who had undergone potentially curative resection for ESCC were immunohistochemically assessed using monoclonal antibodies against HIF-1α, p53, and VEGF.

Results: Positive rates of HIF-1α, p53, and VEGF expression were 61.7%, 56.7%, and 78.3%, respectively. No significant relationship was found between HIF-1α, p53, VEGF expression, and the analyzed clinicopathological parameters. There was no significant correlation between the expression of HIF-1α, p53, and VEGF. Univariate analysis revealed that overexpression of HIF-1α was associated with poor disease-free and overall survival (P = 0.023 and 0.01, respectively). Multivariate analysis demonstrated that upregulation of HIF-1α is an independent predictor for poor overall survival (P = 0.044).

Conclusions: HIF-1α was a useful independent prognostic factor for surgically treated ESCC. Further studies with larger sample size are required to determine the relationship between the expression of HIF-1α, p53, VEGF, and clinicopathological parameters.

Keywords: Esophageal squamous cell carcinoma; hypoxia-inducible factor 1α; p53; vascular endothelial growth factor.

MeSH terms

  • Aged
  • Biomarkers, Tumor / metabolism*
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / pathology*
  • Esophageal Neoplasms / surgery
  • Esophageal Squamous Cell Carcinoma / metabolism
  • Esophageal Squamous Cell Carcinoma / pathology*
  • Esophageal Squamous Cell Carcinoma / surgery
  • Female
  • Humans
  • Hypoxia / pathology
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Lymphatic Metastasis
  • Male
  • Neoplasm Grading
  • Neoplasm Staging
  • Survival Rate
  • Tumor Suppressor Protein p53 / metabolism*
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • Biomarkers, Tumor
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A