A novel cuproptosis-related lncRNAs signature predicts prognostic and immune of bladder urothelial carcinoma

Abstract

Bladder Urothelial Carcinoma (BLCA) remains the most common urinary system tumor, and its prognosis is poor. Cuproptosis is a recently discovered novel cell death involved in the development of tumor cells. However, the use of cuproptosis to predict the prognosis and immunity of Bladder Urothelial Carcinoma remains largely unclear, and this study was designed to verify cuproptosis-related long non-coding RNAs (lncRNAs) to estimate the prognosis and immunity of Bladder Urothelial Carcinoma. In our study, we first defined the expression of cuproptosis-related genes (CRGs) in BLCA, and 10 CRGs were up- or downregulated. We then constructed a co-expression network of cuproptosis-related mRNA and long non-coding RNAs using RNA sequence data from The Cancer Genome Atlas Bladder Urothelial Carcinoma (TCGA-BLCA), clinical features and mutation data from BLCA patients to obtain long non-coding RNAs by Pearson analysis. Afterward, univariate and multivariate COX analysis identified 21 long non-coding RNAs as independent prognostic factors and used these long non-coding RNAs to construct a prognostic model. Then, survival analysis, principal component analysis (PCA), immunoassay, and comparison of tumor mutation frequencies were performed to verify the accuracy of the constructed model, and GO and KEGG functional enrichment analysis was used to verify further whether cuproptosis-related long non-coding RNAs were associated with biological pathways. The results showed that the model constructed with cuproptosis-related long non-coding RNAs could effectively evaluate the prognosis of BLCA, and these long non-coding RNAs were involved in numerous biological pathways. Finally, we performed immune infiltration, immune checkpoint and drug sensitivity analyses on four genes (TTN, ARID1A, KDM6A, RB1) that were highly mutated in the high-risk group to evaluate the immune association of risk genes with BLCA. In conclusion, the cuproptosis-related lncRNA markers constructed in this study have evaluation value for prognosis and immunity in BLCA, which can provide a certain reference for the treatment and immunity of BLCA.

Chromatin modifiers in human disease: from functional roles to regulatory mechanisms

“…AT-interacting domain-rich protein 1A (ARID1A) is one of the SWI/SNF complex subunits that control the development and regeneration of the bladder urothelium. ARID1A mutation leads to self-inactivation but induces the occurrence of bladder tumors and affects the immune invasion process of bladder cancer, and ARID1A mutation is associated with poor prognosis [162][163][164]. Moreover, the deletion of ARID1A in the tumor microenvironment activates cancer-associated fibroblasts and drives the proliferation and migration of lung cancer cells, but inhibits tumor cell autophagy and enhances the sensitivity of immunosuppressive therapy for EGFR-mutant lung adenocarcinoma [165,166].…”