Rac3 Expression and its Clinicopathological Significance in Patients With Bladder Cancer

Pathol Oncol Res. 2021 Mar 30:27:598460. doi: 10.3389/pore.2021.598460. eCollection 2021.

Abstract

Background: Ras-related C3 botulinum toxin substrate 3 (Rac3) is overexpressed in malignancies and promotes tumor progression. However, the correlations between Rac3 expression and the clinicopathological characteristics and prognoses of patients with bladder cancer (BC) remain unclear. Methods: Data from The Cancer Genome Atlas (TCGA) were used to analyze Rac3 expression in BC and normal bladder tissues and validated using the Oncomine database, quantitative real-time PCR (qRT-PCR) and western blot. The Kaplan-Meier method was used to analyze the relationship between Rac3 expression and the prognosis of patients with BC. Cox univariate and multivariate analyses of BC patients overall survival (OS) were performed. Signaling pathways that potentially mediate Rac3 activity in BC were then analyzed by gene set enrichment analysis (GSEA). Results: The Rac3 expression in BC tissues was significantly higher than that in normal bladder tissues. Rac3 expression was significantly correlated with grade and stage. Overexpression of Rac3 was associated with a poor prognosis. GSEA showed that the cell cycle, DNA replication, p53 signaling pathway and mismatch repair were differentially enriched in the high Rac3 expression phenotype. The qRT-PCR and western blot results confirmed that the Rac3 expression in BC tissues was higher than that in normal bladder tissues. Conclusion: Rac3 is highly expressed in BC, which is related to the advanced clinicopathological variables and adverse prognosis of patients with BC. These results provide a new therapeutic target for BC.

Keywords: GSEA; Rac3; TCGA; bladder cancer; clinicopathological significance; prognose.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Signal Transduction
  • Survival Rate
  • Transcriptome*
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / metabolism
  • Urinary Bladder Neoplasms / pathology*
  • rac GTP-Binding Proteins / genetics
  • rac GTP-Binding Proteins / metabolism*

Substances

  • Biomarkers, Tumor
  • RAC3 protein, human
  • rac GTP-Binding Proteins