Low Expression of Toll-like Receptor 4 Is Associated With Poor Prognosis in Bladder Cancer

Anticancer Res. 2019 Feb;39(2):703-711. doi: 10.21873/anticanres.13166.

Abstract

Background/aim: The aim of this study was to elucidate the relationship between the progression of bladder cancer (BCa) and TLR4 expression.

Materials and methods: The relationship between TLR4 expression and prognosis of BCa patients was analyzed using a publicly available database and immunohistochemical staining of clinical samples. The effect of TLR4 knockdown was also examined on the invasive capabilities of BCa cells. Finally, to investigate the biological function of TLR4, the gene expression profile of TLR4-depleted BCa cells was analyzed by microarray analysis.

Results: Expression of TLR4 was inversely associated with prognosis of patients with invasive BCa, and depletion of TLR4 significantly enhanced the invasive capability of BCa cells. Gene expression profiling revealed that depletion of TLR4 led to high expression of epithelial differentiation genes. Furthermore, expression of TLR4 was found to be extremely low in areas of squamous differentiation.

Conclusion: Low TLR4 expression was correlated with tumor progression.

Keywords: Bladder cancer; Toll-like receptor 4; squamous differentiation.

MeSH terms

  • Aged
  • Biomarkers, Tumor / metabolism*
  • Cell Differentiation
  • Cell Line, Tumor
  • Computational Biology
  • Disease Progression
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Oligonucleotide Array Sequence Analysis
  • Prognosis
  • RNA, Small Interfering / metabolism
  • Toll-Like Receptor 4 / metabolism*
  • Urinary Bladder Neoplasms / diagnosis
  • Urinary Bladder Neoplasms / metabolism*
  • Urinary Bladder Neoplasms / pathology

Substances

  • Biomarkers, Tumor
  • RNA, Small Interfering
  • TLR4 protein, human
  • Toll-Like Receptor 4