Development and Validation of an Immune-Related Prognostic Signature for Laryngeal Squamous Cell Carcinoma

Background: Laryngeal squamous cell carcinoma (LSCC) is a highly aggressive malignancy with poor prognosis, particularly in advanced stages. While traditional treatments have improved survival rates, reliable biomarkers for prognosis remain limited. Methods: We analyzed RNA-seq data of LSCC patients from the Cancer Genome Atlas (TCGA) and validated the results using the Gene Expression Omnibus (GEO) dataset (GSE27020), clinical samples, and LSCC cell lines. Differentially expressed immune-related genes (DEIRGs) were identified using the "limma" R package. A prognostic signature was developed by integrating univariate Cox analysis, least absolute shrinkage and selection operator (LASSO) regression, and multivariate Cox analysis. The signature's predictive performance was validated using Kaplan-Meier survival analysis and receiver operating characteristic (ROC) curves. Results: A three-gene immune-related prognostic signature comprising TNFRSF4, PPARG, and PDGFA was established. In the training cohort, the model stratified patients into high- and low-risk groups with significantly different overall survival (HR = 5.81, 95% CI: 2.56-13.22, p < 0.001), with apparent 1-, 2-, and 3-year AUC values of 0.838, 0.895, and 0.947, respectively. Predictive performance was further evaluated in the TCGA testing cohort, the full TCGA cohort, and the GSE27020 cohort. Functional enrichment analysis revealed that the signature genes are involved in immune regulation and tumor progression. Conclusions: This study identified and validated a novel three-gene immune-related prognostic signature for LSCC, offering a practical tool for individualized prognosis and personalized treatment strategies. The signature provides insights into immune-related mechanisms in LSCC, presenting potential targets for therapeutic intervention.