Abstract
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.
Highlights
Bladder cancer (BC) is one of the most prevalent cancers, accounting for approximately 200,000 deaths per year worldwide, with preponderance in men compared with women (4:1) (Bray et al, 2018)
We found a significant association between the prognosis of patients with Bladder urothelial carcinoma (BLCA) and the energy metabolism-related signature, which could serve as an independent clinicopathological prognostic factor
To explore the role of energy metabolism status in BLCA, we obtained a cohort of 408 patients using RNA sequencing data and clinicopathological information from the the Cancer Genome Atlas (TCGA) database
Summary
Bladder cancer (BC) is one of the most prevalent cancers, accounting for approximately 200,000 deaths per year worldwide, with preponderance in men compared with women (4:1) (Bray et al, 2018). More than 90% of BC cases are transitional cell carcinomas, known as bladder urothelial carcinoma (BUC or BLCA), accounting for the majority of primary BC cases (Potts et al, 2017). In NMIBC patients, carcinoma in situ (CIS), high-grade T1, and high-grade Ta tumors are considered to have a high risk of tumor recurrence and disease progression. In the clinical management of BLCA, the prognosis of tumors often depends on the histopathology and stage of cancer (Kamat et al, 2016; Babjuk et al, 2017), which provides a simple risk stratification but cannot explain the different prognoses and outcomes of patients with the same histopathology and tumor stage. 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
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