Background: Bladder cancer (BLCA) is a malignant urothelial carcinoma with a high mortality rate. Ferroptosis is a new type of programmed cell death and functions in suppressing tumor growth and progression. However, few studies focus on ferroptosis and BLCA.
Materials and methods: We explored the potential oncogenic roles of ferroptosis-related genes in BLCA based on multiple public datasets. We then used univariate and multivariate cox regression to build a new survival model based on ferroptosis-related genes to predict the survival of BLCA.
Results: We found that 23 ferroptosis-related genes had a strong correlation with each other in BLCA. Eight ferroptosis-related genes, CDKN1A, HSPA5, NFE2L2, MT1G, FANCD2, CISD1, TFRC, NCOA4, had a significantly different expression and heat-map. HSPA5 and CISD1 have a statistically significant difference in OS and DFS. Besides, CISD1 had an ideal nomogram to predict the 1-3-5-year OS (C-index: 0.701, P < .001). Furthermore, HSPA5 and CISD1 had a lower DNA methylation rate than normal tissue and HSPA5 had a positive connection with TMB (P = .02). In addition, HSPA5 participated in the DNA replication and P53 signaling pathway, and CISD1 mediated the oxidative phosphorylation and positive regulation of the intrinsic apoptotic signaling pathway.
Conclusion: Ferroptosis-related genes had a strong correlation with BLCA, notably, HSPA5 and CISD1 may play a role in inducing ferroptosis to suppress bladder tumorigenesis and CISD1 can be a novel prognostic biomarker as well as an effective target for diagnosis and treatment in BLCA.
Keywords: Biomarcador; Biomarker; Bladder cancer; CISD1; Cáncer de vejiga; Ferroptosis; HSPA5; Modelo de supervivencia; Survival model.
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