Harnessing Ubiquitin-Proteasome System-Related Genes to Identify Subtypes of Bladder Cancer and Reveal Immune Landscape

The ubiquitin-proteasome system (UPS) is intricately linked to the growth and metastasis of numerous types of cancer. However, current analysis on the function and impact of UPS in bladder cancer (BLCA) is still sparse. First, univariate Cox regression analysis was applied to screen survival-associated UPS-related genes (UPSGs). Then, based on the expression of survival-related UPSGs, BLCA patients were divided into three clusters through unsupervised cluster analysis, and the overall survival rate of Cluster 1 and Cluster 3 was higher than that of Cluster 2, but there was no survival difference between Cluster 1 and Cluster 3. Therefore, Cluster 1 + Cluster 3 (Cluster A) and Cluster 2 (Cluster B) were selected for subsequent analysis. The differentially expressed genes of the two clusters were predominantly enriched in signaling pathways such as the Calcium signaling pathway and Cytokine-cytokine receptor interaction. An immune microenvironment analysis revealed that Cluster B patients were characterized by highly infiltrated immunosuppressive cells (M2 macrophages and Tregs) as well as high expression of immune checkpoint genes (such as BTLA and CTLA4). Furthermore, Cluster B exhibited a higher TIDE score. Somatic mutations demonstrated that the mutation rate of Cluster B was higher than that of Cluster A. In addition, candidate drugs for two clusters of patients were predicted, with Lapatinib, Doramapimod, and SCH772984 may be potential drugs for Cluster A patients. Luminespib, Staurosporine, and Dasatinib may be more suitable for Cluster B patients. The study provides a reference for guiding the clinical treatment of BLCA patients.