Effects of CLIC family expression levels on the prognosis and tumor immune microenvironment of Bladder Cancer

Abstract Purpose CLIC family members act as tumor suppressors or oncogenes in multiple cancer processes. However, the CLIC family of genes in bladder cancer is currently not well characterized. Methods 375 bladder cancer samples containing RNASeq and clinical data were downloaded from the TCGA database. The present study aimed to analyze the role of CLIC members in bladder cancer using bioinformatics analysis. Quantitative real-time PCR and Western blotting were performed to quantify gene and protein expression, respectively. The impact of CLIC members on the characteristics of the TME was also analyzed. Results The differences in expression among the 5 CLIC family members were statistically significant in bladder cancer, including CLIC1, CLIC2, CLIC3, CLIC4, and CLIC5. CLIC3 and CLIC4 were two independent prognostic factors associated with poor overall survival in patients with bladder cancer. The results of q-PCR and western bloting showed that CLIC3 was overexpressed in bladder cancer and CLIC4 was expressed at low level in bladder cancer. Similar trends were observed in both q-PCR and western blotting. Among the tumor microenvironmental scores, immune cell infiltration, and immune checkpoint genes, CLIC3 and CLIC4 were associated. CLIC3 and CLIC4 were able to influence bladder cancer chemotherapy sensitivity as well as immunotherapy efficacy. Conclusion A study like this improves the method of assessing bladder cancer patients' prognoses, and would help optimize chemotherapeutic strategies as well as immunotherapy efficacy in consideration of the expression of CLIC3 and CLIC4.