Ferroptosis-related long non-coding RNA signature predicts the prognosis of bladder cancer

Ferroptosis is an iron-dependent programmed cell death modality that may have a tumor-suppressive 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 predictor for bladder cancer (BCa).

We retrieved BCa-related transcriptome information and clinical information from the TCGA database and ferroptosis-related gene sets from the FerrDb database. Least absolute shrinkage and selection operator regression (LASSO) and Cox regression models were used to identify and develop predictive models and validate the model accuracy. Finally, we explored the inter-regulatory relationships between ferroptosis-related genes and immune cell infiltration, immune checkpoints, and m⁶A methylation genes.

Kaplan-Meier analyses screened 11 differentially expressed lncRNAs associated with poor BCa prognosis. The signature (AUC = 0.720) could be utilized to predict BCa prognosis. Additionally, GSEA revealed immune and tumor-related pathways 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 differentially expressed between the two risk groups. m⁶A methylation-related genes were significantly differentially expressed between the two risk groups.

A new ferroptosis-associated lncRNAs signature developed for predicting the prognosis of BCa patients will improve the treatment and management of BCa patients.