Exploration of the Critical Roles and Molecular Mechanisms of KIF2C and GPX4 Genes in Head and Neck Squamous Cell Carcinoma

Background Head and neck squamous cell carcinoma (HNSCC) is a highly invasive and heterogeneous malignancy with poorly understood molecular mechanisms. This study aims to investigate the potential roles of ferroptosis-related core genes, KIF2C and GPX4, in HNSCC progression and their impact on patient prognosis through bioinformatics analysis. Methods This study utilized the HNSCC gene expression dataset (GSE10774) from the gene expression omnibus (GEO) database to identify differentially expressed genes (DEGs). Weighted gene co-expression network analysis (WGCNA), protein-protein interaction (PPI) network construction, and functional enrichment analysis (GO and KEGG) were performed to identify core genes associated with ferroptosis pathways. Survival analysis was conducted using the The Cancer Genome Atlas (TCGA) database, and heatmaps and comparative toxicogenomics database (CTD) analyses were used to validate the expression patterns and functions of key genes. RT-PCR was performed to verify the expression of hub genes. Results KIF2C and GPX4 were significantly overexpressed in HNSCC tissues and strongly associated with poor prognosis. Functional enrichment analysis revealed that these genes were primarily enriched in ferroptosis, P53 signaling pathways, and MAPK signaling pathways. Further analyses suggested that KIF2C may promote tumor progression by regulating cell division and anti-apoptotic pathways, while GPX4 enhances tumor cell survival by inhibiting ferroptosis. RT-PCR showed that the relative expression of hub genes was differently expressed in cancer cells. Conclusion The overexpression of KIF2C and GPX4 may represent critical molecular mechanisms underlying HNSCC progression and poor prognosis. This study provides new perspectives and potential targets for the diagnosis and targeted therapy of HNSCC. Future studies are required to validate their functions and mechanisms in vitro and in vivo.