Upregulation of RAC3 in bladder cancer predicts adverse clinical outcome and increased tumor immune response.

The relationship between RAC3 expression and clinical outcome in bladder cancer (BLCA) was uncertain. In this study, the expression level of RAC3 in BLCA and its clinical outcome were analyzed through various independent public databases. The mRNA expression level of RAC3 in BLCA and normal bladder was evaluated from the Gene Expression Omnibus (GEO), Oncomine, and The Cancer Genome Atlas (TCGA) database. The protein expression of RAC3 in BLCA and normal bladder was investigated from immunohistochemical images through the Human Protein Atlas (HPA) database. Next, gene tumor immune analyses were performed. Furthermore, gene set enrichment analysis (GESA) by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes enrichment (KEGG) for RAC3 and its co-expressed genes were performed. Then, GESA was also performed to validate the KEGG pathways by the different expression of RAC3 in BLCA. The results indicated that, compared with normal bladder, the mRNA and protein expression of RAC3 in BLCA were both significantly higher than those of normal bladder tissues (P<0.05). The tumor immune analyses indicated RAC3 was associated with microsatellite instability, tumor mutational burden, tumor immune microenvironment, and immune cell infiltration level evaluation (P<0.05). The survival analysis result demonstrated that upregulation of RAC3 was associated with adverse survival in BLCA (P<0.05). Taken together, these findings suggest that RAC3 may be associated with adverse clinical outcome and increased tumor immune response in BLCA, and may be a prognostic and immunotherapy marker for BLCA.