Illuminating the role of VEGFA and EGFR in head and neck squamous cell carcinoma through the multi-omics data integration.

Objectives: To investigate the functions of 2 crucial wound-healing genes, vascular endothelial growth factor-A (VEGFA) and epidermal growth factor receptor (EGFR) in head and neck squamous cell carcinoma (HNSCC).

Methods: This observational study, carried out between January and August 2024 in Saudi Arabia, involved 20 HNSCC and 10 normal oral cell lines sourced from The American type culture collection. Cell lines were cultured and gene expression was analyzed via RT-qPCR and Western blotting. Promoter methylation and mutational analyses were carried out using databases like UALCAN and cBioPortal. Functional assays, including cell proliferation, colony formation, and wound healing, were carried out to evaluate the effects of VEGFA and EGFR gene silencing using siRNA.

Results: Expression analysis of 20 HNSCC cell lines showed significant upregulation of VEGFA and EGFR, confirming their potential as biomarkers. Receiver operating characteristic curve analysis further supported their discriminatory capabilities. Promoter methylation analysis revealed hypomethylation of both genes in HNSCC. Validation confirmed elevated mRNA and protein expression, especially in advanced stages. Mutational analysis indicated infrequent mutations. A prognostic model showed a correlation between higher VEGFA and EGFR expression and reduced overall survival. Knockdown experiments in human oral squamous carcinoma-3 cells reduced growth, and DrugBank identified Simvastatin as a potential therapeutic, with molecular docking showing strong interactions.

Conclusion: This study highlights VEGFA and EGFR as diagnostic, prognostic, and therapeutic targets in HNSCC.