Insulin-Like Growth Factor Binding Protein 5-A Probable Target of Kidney Renal Papillary Renal Cell Carcinoma

Biomed Res Int. 2019 Nov 11:2019:3210324. doi: 10.1155/2019/3210324. eCollection 2019.

Abstract

Kidney renal papillary renal cell carcinoma (KIRP) accounts for 10-15% of renal cell carcinoma (RCC). The need to find more therapeutic targets for KIRP is urgent because most targeted drugs have limited effects on advanced KIRP. Insulin-like growth factor (IGF) binding protein 5 (IGFBP5) is a secreted protein related to cell proliferation, cell adhesion, cell migration, the inflammatory response and fibrosis; these functions are independent of IGF. In our study, we determined the expression and functions of IGFBP5 with data from the database of The Cancer Genome Atlas (TCGA). We found that IGFBP5 is down regulated in KIRP kidney tissues compared to its expression in control tissues and that the expression of IGFBP5 is negatively related to patient survival. Bioinformatic analysis showed the probable processes and pathways involved in altered IGFBP5 expression, including blood vessel development, the cellular response to growth factor stimulus, the response to transforming growth factor β (TGF-β), and extracellular matrix organization. We proposed that VEGFA and TGF-β act as upstream regulatory factors of IGFBP5 and verified this in the Caki-2 cell line. Based on our results, we suggest that IGFBP5 might be a therapeutic target of KIRP.

MeSH terms

  • Carcinoma, Renal Cell / genetics
  • Carcinoma, Renal Cell / metabolism*
  • Carcinoma, Renal Cell / mortality
  • Carcinoma, Renal Cell / pathology
  • Cell Line, Tumor
  • Databases, Genetic*
  • Disease-Free Survival
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Insulin-Like Growth Factor Binding Protein 5 / biosynthesis*
  • Insulin-Like Growth Factor Binding Protein 5 / genetics
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / metabolism*
  • Kidney Neoplasms / pathology
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • Survival Rate
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • IGFBP5 protein, human
  • Insulin-Like Growth Factor Binding Protein 5
  • Neoplasm Proteins
  • Transforming Growth Factor beta
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A