Vascular Endothelial Growth Inhibitor, a Cytokine of the Tumor Necrosis Factor Family, is Associated With Epithelial-Mesenchymal Transition in Renal Cell Carcinoma

Appl Immunohistochem Mol Morphol. 2018 Nov/Dec;26(10):727-733. doi: 10.1097/PAI.0000000000000517.

Abstract

Previous studies have revealed that the activation of the epithelial-mesenchymal transition (EMT) endows metastatic properties upon cancer cells to promote invasion and migration. In this study, immunohistochemical analysis was performed in 50 cases of clear cell renal cell carcinoma (RCC) and paired normal kidney tissues. We detected the expression of vascular endothelial growth inhibitor (VEGI) and EMT markers (E-cadherin, fibronectin, and Slug) and recorded the clinical, pathologic, and follow-up (median follow-up: 79.0 mo) information. The expression of VEGI and E-cadherin was significantly lower in RCC tissues compared with normal kidney tissues (P<0.001). However, the expression of fibronectin and Slug was higher in RCC tissues (P<0.05). VEGI and EMT marker expression marginally differed in tumor size and stage. Significant differences were found in the pathologic grade (P<0.05). The Spearman correlation analysis suggested a positive correlation between VEGI and E-cadherin (r=0.451, P<0.01). A negative correlation was shown between VEGI and fibronectin (r=-0.465, P<0.01). There was also a negative correlation between VEGI and Slug (r=-0.758, P<0.01). During the 79.0 months (range, 7 to 119 mo) of follow-up, 6 patients died due to RCC, and the tumor-free survival rate was 88% (44/50). We did not find a significant correlation between VEGI/EMT markers (E-cadherin, fibronectin, and Slug) and overall survival (P>0.05). Our findings indicate that VEGI plays an important role in EMT in RCC. It suggests that VEGI may be investigated as a disease biomarker and therapeutic target in RCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Renal Cell* / metabolism
  • Carcinoma, Renal Cell* / mortality
  • Carcinoma, Renal Cell* / pathology
  • Disease-Free Survival
  • Epithelial-Mesenchymal Transition*
  • Female
  • Humans
  • Kidney Neoplasms* / metabolism
  • Kidney Neoplasms* / mortality
  • Kidney Neoplasms* / pathology
  • Male
  • Middle Aged
  • Neoplasm Proteins / metabolism*
  • Survival Rate
  • Tumor Necrosis Factor Ligand Superfamily Member 15 / metabolism*

Substances

  • Biomarkers, Tumor
  • Neoplasm Proteins
  • TNFSF15 protein, human
  • Tumor Necrosis Factor Ligand Superfamily Member 15