Molecular factors regulating E-cadherin expression in urothelial bladder cancer and their correlations with the clinicopathological features

Mol Biol Rep. 2017 Aug;44(4):365-377. doi: 10.1007/s11033-017-4118-z. Epub 2017 Aug 14.

Abstract

This study aimed to assess the expression of S100A4, Twist and E-cadherin (mRNA and protein) in urothelial bladder cancer, investigate the correlation between them and evaluate their association with the clinicopathological features of the disease. The study included 54 patients diagnosed as urothelial bladder cancer of different stages and grades. The expression levels of S100A4, Twist and E-cadherin (mRNA and protein) in tissue samples were determined by quantitative RT-PCR and immunohistochemistry. The expression of S100A4 and Twist was significantly upregulated while E- cadherin was significantly downregulated in urothelial bladder cancer tissues compared to the adjacent surrounding normal bladder tissues at both mRNA and protein levels (p < 0.001). Expression levels of S100A4 and Twist were significantly higher in recurrent tumor than in non-recurrent tumors (p < 0.001) while the expression level of E-cadherin was significantly lower in recurrent tumors than in non-recurrent tumors at both mRNA and protein levels (p < 0.001). There was a significant positive correlation between S100A4 and Twist expressions (r = 0.875, p < 0.001) while significant negative correlations were found between E- cadherin and S100A4 expressions(r=- 0.803, p < 0.001) and between E-cadherin and Twist (r = -0.809, p < 0.001). Up-regulation of S100A4 and Twist and down-regulation of E-cadherin in urothelial bladder cancer tissues compared to adjacent normal tissues were observed. There was a significant negative correlation between S100A4 and E- cadherin and between E- cadherin and Twist expression. However, there was a significant positive correlation between S100A4 and Twist expressions. Furthermore, the alterations in the gene expression were associated with disease stage and grade.

Keywords: E-cadherin; Immunohistochemistry; Quantitative RT-PCR; S100A4; Twist; Urothelial bladder cancer.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, CD
  • Biomarkers, Tumor / genetics
  • Cadherins / genetics*
  • Cadherins / metabolism
  • Carcinoma, Transitional Cell / genetics
  • Egypt
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / genetics
  • Nuclear Proteins / genetics
  • Prognosis
  • RNA, Messenger / metabolism
  • Real-Time Polymerase Chain Reaction
  • S100 Calcium-Binding Protein A4 / genetics*
  • S100 Calcium-Binding Protein A4 / metabolism
  • Twist-Related Protein 1 / genetics*
  • Twist-Related Protein 1 / metabolism
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / metabolism

Substances

  • Antigens, CD
  • Biomarkers, Tumor
  • CDH1 protein, human
  • Cadherins
  • Nuclear Proteins
  • RNA, Messenger
  • S100 Calcium-Binding Protein A4
  • Twist-Related Protein 1
  • S100A4 protein, human