Relationships of Ferroptosis and Pyroptosis-Related Genes with Clinical Prognosis and Tumor Immune Microenvironment in Head and Neck Squamous Cell Carcinoma

Abstract

Ferroptosis and pyroptosis are two new programmed cell death (PCD) modes discovered in recent years. However, the potential value of ferroptosis and pyroptosis-related genes (FPRGs) in prognosis prediction and the tumor immune microenvironment of head and neck squamous cell carcinoma (HNSCC) is still unclear. We obtained 21 significant FPRGs based on the training dataset (TCGA- HNSC) using the univariate Cox and differential expression analysis. The TCGA- HNSC ( $n=502$ ) dataset was clustered into two group (clusters A and B) based on the 21 significant FPRGs. 1467 differentially expressed genes (DEGs) between cluster A and B were put into univariate Cox and Least absolute shrinkage and selection operator (LASSO) analysis to build a risk model. The predictive capability of the risk model was successfully confirmed by internal validation, external validation, and clinical sample validation. To improve the clinical applicability, a nomogram model combined risk score and clinical information were constructed. Moreover, the patients with lower risk score were characterized by increased immune response and tumor mutation burden (TMB), while the patients with higher risk score were characterized by increased TP53 mutation rate. In conclusion, our comprehensive analysis of the FPRGs revealed their significant role in prognosis prediction and the tumor immune microenvironment. The risk model containing 9 FPRGs could be a potential prognostic markers and effective immunotherapy targets for HNSCC.