Pan-cancer analysis and experiments with cell lines reveal that the slightly elevated expression of DLGAP5 is involved in clear cell renal cell carcinoma progression

Life Sci. 2021 Dec 15:287:120056. doi: 10.1016/j.lfs.2021.120056. Epub 2021 Oct 20.

Abstract

Aims: Discs large-associated protein 5 (DLGAP5), a kinetochore fibers-binding protein, functions as a oncoprotein in many cancers. However, its expression patterns in pan-cancer including clear cell renal cell carcinoma (ccRCC) are not analyzed. Herein, we aimed to evaluate its expression in more common cancers, especially in ccRCC.

Main methods: Data from Genotype-Tissue Expression, The Cancer Genome Atlas, and Tumor Immune Estimation Resource were used to analyze the DLGAP5 expression in normal tissues, cancer cell lines, and cancer tissues, as well as the immune infiltration levels. The analysis results were verified with ccRCC cell lines via RNAi, western blotting, and the cytological analysis.

Key findings: Low DLGAP5 expression in 31 types of normal tissues, the upregulation in 21 cancer cell lines, and the significant elevated expression in 26 types of cancers, were found, Surprisingly, kidney cancer including ccRCC, DLGAP5 exhibited a slightly elevated but statistically significant expression among 26 types of cancers. In addition, elevated DLGAP5 expression was significantly positive correlated with immune infiltration level in ccRCC. The survival probability of some cancers including kidney cancer, clinical TNM stage of ccRCC patients were significantly related to upregulated DLGAP5 expression. The experiments results showed DLGAP5 upregulation in ccRCC tissues and the cell lines, its knockdown inhibited the cells viability and proliferation, and compromised the cells migration and invasion.

Significance: Elevated DLGAP5 expression occurred in common cancers. However, its slightly upregulated expression is related with ccRCC progression, it is therefore a prognostic risk factor for ccRCC, but not an independent factor.

Keywords: Clear cell renal cell carcinoma (ccRCC); DLGAP5; GTEx; Pan-cancer; TCGA; TIMER.

MeSH terms

  • Biomarkers, Tumor / biosynthesis*
  • Biomarkers, Tumor / genetics
  • Carcinoma, Renal Cell / genetics
  • Carcinoma, Renal Cell / metabolism*
  • Carcinoma, Renal Cell / pathology
  • Cell Line, Tumor
  • Disease Progression*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / metabolism*
  • Kidney Neoplasms / pathology
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics

Substances

  • Biomarkers, Tumor
  • DLGAP5 protein, human
  • Neoplasm Proteins