Ferroptosis-related lncRNA signature predicts prognosis and immune microenvironment remodeling in laryngeal squamous cell carcinoma

Ferroptosis is an iron-dependent regulated cell death process increasingly recognized as a modulator of tumor progression and antitumor immunity. However, the role of ferroptosis-related long non-coding RNAs (lncRNAs) in shaping the immune microenvironment of laryngeal squamous cell carcinoma (LSCC) remains unclear. TCGA transcriptomic and clinical data were analyzed to identify ferroptosis-related lncRNAs (FRLs) through co-expression analysis. A prognostic signature was constructed using a predefined LASSO Cox-based modelling strategy followed by multivariate Cox regression. Survival performance was evaluated by Kaplan-Meier analysis, time-dependent ROC curves, calibration analysis, and the concordance index (C-index). Tumor immune infiltration was assessed using ssGSEA and ESTIMATE algorithms, and associations with immune checkpoint expression were examined. A four-lncRNA ferroptosis-related signature stratified LSCC patients into prognostically distinct groups and remained an independent predictor of overall survival in the TCGA-derived cohort. High-risk tumors exhibited reduced infiltration of activated CD8 + T cells, NK cells, and dendritic cells, along with enrichment of MDSCs. The risk score showed a weak-to-moderate negative correlation with PD-L1 expression and was associated with reduced adaptive immune signatures, suggesting an immune-cold phenotype that requires further experimental validation. This study identifies a ferroptosis-related lncRNA signature associated with survival and immune microenvironment features in LSCC. These findings provide a hypothesis-generating framework for future experimental and clinical studies integrating ferroptosis-related biomarkers with immunotherapy research.