Integrated Analysis of Energy Metabolism Signature-Identified Distinct Subtypes of Bladder Urothelial Carcinoma

Background: Bladder urothelial carcinoma (BLCA) is the most common type of bladder cancer. In this study, the correlation between the metabolic status and the outcome of patients with BLCA was evaluated using data from the Cancer Genome Atlas and Gene Expression Omnibus datasets. Methods: The clinical and transcriptomic data of patients with BLCA were downloaded from the Cancer Genome Atlas and cBioPortal datasets, and energy metabolism-related gene sets were obtained from the Molecular Signature Database. A consensus clustering algorithm was then conducted to classify the patients into two clusters. Tumor prognosis, clinicopathological features, mutations, functional analysis, ferroptosis status analysis, immune infiltration, immune checkpoint-related gene expression level, chemotherapy resistance, and tumor stem cells were analyzed between clusters. An energy metabolism-related signature was further developed and verified using data from cBioPortal datasets. Results: Two clusters (C1 and C2) were identified using a consensus clustering algorithm based on an energy metabolism-related signature. The patients with subtype C1 had more metabolism-related pathways, different ferroptosis status, higher cancer stem cell scores, higher chemotherapy resistance, and better prognosis. Subtype C2 was characterized by an increased number of advanced BLCA cases and immune-related pathways. Higher immune and stromal scores were also observed for the C2 subtype. A signature containing 16 energy metabolism-related genes was then identified, which can accurately predict the prognosis of patients with BLCA. Conclusion: We found that the energy metabolism-associated subtypes of BLCA are closely related to the immune microenvironment, immune checkpoint-related gene expression, ferroptosis status, CSCs, chemotherapy resistance, prognosis, and progression of BLCA patients. The established energy metabolism-related gene signature was able to predict survival in patients with BLCA.