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

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Abstract

Background 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. Methods TCGA transcriptomic and clinical data were analyzed to identify ferroptosis-related lncRNAs (FRLs) through co-expression analysis. A prognostic signature was constructed using LASSO and multivariate Cox regression. Survival performance was evaluated by Kaplan–Meier analysis, time-dependent ROC curves, and calibration analysis. Tumor immune infiltration was assessed using ssGSEA and ESTIMATE algorithms, and associations with immune checkpoint expression were examined. Results A four-lncRNA ferroptosis-related signature robustly stratified LSCC patients into prognostically distinct groups and remained an independent predictor of overall survival. High-risk tumors exhibited reduced infiltration of activated CD8 + T cells, NK cells, and dendritic cells, along with enrichment of MDSCs. Risk score was negatively correlated with PD-L1 expression and adaptive immune signatures, suggesting a ferroptosis-associated immune-cold phenotype. Conclusions This study identifies a ferroptosis-related lncRNA signature that not only predicts survival but also reflects coordinated regulation of ferroptosis susceptibility and tumor immune microenvironment remodeling in LSCC. These findings provide a potential framework for integrating ferroptosis-targeted strategies with immunotherapy.

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