Ferroptosis-Related Long Non-Coding RNA Signature Predicts the Prognosis of Bladder Cancer
Abstract Background: Ferroptosis is an iron-dependent programmed cell death modality that may have a tumor suppressor function. Therefore, regulating ferroptosis in tumor cells could serve as a novel therapeutic approach. This article focuses on ferroptosis-associated long non-coding RNAs (lncRNAs) and their potential application as a prognostic model for bladder cancer (BCa). Methods: We retrieved bladder cancer-related transcriptome information and clinical information from the TCGA database and ferroptosis-related gene sets from the FerrDb database. Minimum absolute shrinkage and selection operator regression and Cox regression models were used to identify and develop predictive models and validate the models' accuracy. Finally, we explore the inter-regulatory relationships between ferroptosis-related genes and immune cell infiltration, immune checkpoints, and m6A methylation genes. Results: Kaplan-Meier analyses revealed 11 differentially expressed lncRNAs associated with poor BCa prognosis. This signature (AUC = 0.720) could potentially be utilized to predict BCa prognosis. Our risk assessment model outperformed traditional clinicopathological features in predicting BCa prognosis. Additionally, GSEA revealed immune and tumor-related pathways in individuals in the low-risk group. TCGA showed that the p53 signaling pathway,ferroptosis,Kaposi sarcoma−associated herpesvirus infection,IL−17 signaling pathway,MicroRNAs in cancer,TNF signaling pathway,PI3K−Akt signaling pathway and HIF−1 signaling pathway were significantly different from those in the high-risk group. Immune checkpoints, such as PDCD-1 (PD-1), CTLA4, and LAG3, were also differentially expressed between the two risk groups. m6A methylation-related genes were likewise significantly differentially expressed between the two risk groups.Conclusion: A new ferroptosis-associated lncRNAs signature on the prognosis of BCa patients will provide new ideas for the treatment and management of BCa patients.