Erythropoietin and erythropoietin receptor in hepatocellular carcinoma: correlation with vasculogenic mimicry and poor prognosis

Int J Clin Exp Pathol. 2015 Apr 1;8(4):4033-43. eCollection 2015.

Abstract

To evaluate erythropoietin (Epo) and erythropoietin receptor (EpoR) expression, its relationship with vasculogenic mimicry (VM) and its prognostic value in human hepatocellular carcinoma (HCC), we examined Epo/EpoR expression and VM formation using immunohistochemistry and CD31/PAS (periodic acid-Schiff) double staining on 92 HCC specimens. The correlation between Epo/EpoR expression and VM formation was analyzed using two-tailed Chi-square test and Spearman correlation analysis. Survival curves were generated using Kaplan-Meier method. Multivariate analysis was performed using Cox regression model to assess the prognostic values. Results showed positive correlation between Epo/EpoR expression and VM formation (P < 0.05). Patients with Epo or EpoR expression exhibited poorer overall survival (OS) than Epo-negative or EpoR-negative patients (P < 0.05). Epo-positive/VM-positive and EpoR-positive/VM-positive patients had the worst OS (P < 0.05). In multivariate survival analysis, age, Epo and EpoR were independent prognostic factors related to OS. These results will provide evidence for further research on HCC microcirculation patterns and also will provide new possible targets for HCC diagnosis and treatment.

Keywords: Erythropoietin; erythropoietin receptor; hepatocellular carcinoma; prognosis; vasculogenic mimicry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Biomarkers, Tumor / analysis*
  • Carcinoma, Hepatocellular / blood supply
  • Carcinoma, Hepatocellular / chemistry*
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / surgery
  • Chi-Square Distribution
  • Erythropoietin / analysis*
  • Female
  • Hepatectomy
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Liver Neoplasms / blood supply
  • Liver Neoplasms / chemistry*
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology
  • Liver Neoplasms / surgery
  • Male
  • Middle Aged
  • Molecular Mimicry*
  • Multivariate Analysis
  • Platelet Endothelial Cell Adhesion Molecule-1 / analysis
  • Proportional Hazards Models
  • Receptors, Erythropoietin / analysis*
  • Risk Factors
  • Time Factors
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • EPO protein, human
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Receptors, Erythropoietin
  • Erythropoietin