Identification of a Novel Ferroptosis-Related Gene Signature for Prediction of Prognosis in Bladder Urothelial Carcinoma

BACKGROUND: Bladder urothelial carcinoma is the most prevalent type of bladder cancer, characterized by drug resistance, high recurrence rate, and unfavorable prognosis. Ferroptosis is a newly discovered type of non-apoptotic cell death, which has been reported to be strongly correlated with tumor occurrence and development. OBJECTIVE: In this study, we characterized ferroptosis-specific biomarkers to elucidate the association between ferroptosis-related genes (FRGs) and bladder urothelial carcinoma. METHODS: The TCGA and GEO database were adopted to obtain data and corresponding clinicopathological information. Univariate and multivariate cox regression were performed to establish a ferroptosis-related model. Besides, the KM plot visualized prognosis between high risk and low risk groups. Moreover, cBioportal platform was used to gather information on genetic alteration and DNA methylation of hub FRGs in BLCA patients. Additionally, the GSEA software was used to detect the difference in gene expression between high-risk and low-risk subgroups. RESULTS: Six ferroptosis-related genes were identified to be highly correlated with overall survival. Besides, we explored the genetic variations of these FRGs, as well as the correlation between FRG expression and copy number values. Additionally, the DNA methylation status of these FRGs was determined. Moreover, we constructed a ferroptosis risk model with the six FRGs to predict the prognosis of BLCA. The results demonstrated that a higher risk score indicated an unfavorable prognosis. The ferroptosis signature was associated with clinical and molecular characteristics and could be regarded as an independent prognostic factor for BLCA patients. CONCLUSIONS: In summary, we established and verified a ferroptosis risk model which had the potential to independently predict the prognosis of bladder urothelial carcinoma.