Abstract
BACKGROUND: This study explores the role of 5mC regulatory genes in head and neck squamous cell carcinoma (HNSCC), focusing on their association with tumor progression, metastasis, and prognosis. A prognostic model was also developed to predict patient survival. MATERIALS AND METHODS: Using expression profile data from the GEO and TCGA databases, the study analyzed the differential expression of 5mC-related genes, their connection with somatic mutations, and their impact on the immune microenvironment. A prognostic risk model based on these genes was constructed through the differential expression of 5mC-related genes. RESULTS: (1) Several 5mC regulatory factors were found to be abnormally expressed in HNSCC, with a significant association with somatic mutations. (2) Different 5mC methylation regulation patterns showed variations in immune infiltration, immune checkpoint expression, tumor mutation burden, and cancer stem cell gene set expression, potentially influencing immunotherapy effectiveness and prognosis. (3) Prognosis-related risk genes, such as DNMT1 and TET2, were identified as predictors of survival outcomes in HNSCC patients. CONCLUSIONS: The methylation patterns of 5mC regulatory factors are critical in HNSCC progression and are closely linked to tumor microenvironment infiltration. These findings offer new perspectives for treatment strategies and prognosis prediction in HNSCC.