Overexpression of homeobox B-13 correlates with angiogenesis, aberrant expression of EMT markers, aggressive characteristics and poor prognosis in pancreatic carcinoma

Int J Clin Exp Pathol. 2015 Jun 1;8(6):6919-27. eCollection 2015.

Abstract

To investigate the expression of homeobox B (Hoxb)-13 and analyze its relationship with tumor angiogenesis, epithelial-mesenchymal transition (EMT)-associated markers (E-cadherin and vimentin), clinicopathologic data and prognosis in pancreatic carcinoma. Immunohistochemistry was applied to determine the level of Hoxb-13 expression in tumor tissues and surrounding non-tumor tissues from 85 subjects with pancreatic carcinoma. Besides, vascular endothelial growth factor (VEGF), CD31, E-cadherin and vimentin were also detected in tumor tissues by immunostaining. We found that the level of Hoxb-13 expression was significantly higher in pancreatic carcinoma tissues than in paracarcinomatous tissues (P < 0.05). Hoxb-13 staining was positively correlated with VEGF (r = 0.429, P < 0.001) and microvessel density (MVD) (r = 0.454, P < 0.001). Likewise, Hoxb-13 staining was positively correlated with vimentin (r = 0.448, P < 0.001); while it was negatively correlated with E-cadherin (r = -0.405, P < 0.001). High Hoxb-13 expression was associated with aggressive clinicopathological characteristics, worse disease-free survival (DFS) (P < 0.001) and worse overall survival (OS) (P < 0.001). Multivariate analysis showed that Hoxb-13 was an independent predictor for poor DFS (P < 0.001) and OS (P = 0.002). In conclusion, our data show that overexpressed Hoxb-13 is correlated with tumor angiogenesis, aberrant expression of EMT-associated markers and aggressive clinicopathological characteristics, and serves as a promising marker for unfavourable prognosis in pancreatic carcinoma.

Keywords: Homeobox; angiogenesis; epithelial-mesenchymal transition; pancreatic carcinoma; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, CD
  • Biomarkers, Tumor / analysis*
  • Biopsy
  • Cadherins / analysis
  • Carcinoma / chemistry*
  • Carcinoma / mortality
  • Carcinoma / pathology
  • Carcinoma / surgery
  • Disease Progression
  • Disease-Free Survival
  • Epithelial-Mesenchymal Transition*
  • Female
  • Homeodomain Proteins / analysis*
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neovascularization, Pathologic*
  • Pancreatic Neoplasms / chemistry*
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / surgery
  • Platelet Endothelial Cell Adhesion Molecule-1 / analysis
  • Proportional Hazards Models
  • Retrospective Studies
  • Risk Factors
  • Time Factors
  • Treatment Outcome
  • Up-Regulation
  • Vascular Endothelial Growth Factor A / analysis
  • Vimentin / analysis

Substances

  • Antigens, CD
  • Biomarkers, Tumor
  • CDH1 protein, human
  • Cadherins
  • HOXB13 protein, human
  • Homeodomain Proteins
  • Platelet Endothelial Cell Adhesion Molecule-1
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Vimentin