Identification of ETV4 as a prognostic biomarker and correlates with immune cell infiltration in head and neck squamous cell carcinoma

Head and neck squamous cell carcinoma (HNSC) is a common malignant tumor with high incidence and mortality rates. ETS variant transcription factor 4 (ETV4), an important transcription factor, plays a key role in various cancers. However, the role of ETV4 in HNSC remains unclear. This study aimed to explore the potential prognostic value and oncogenic effects of ETV4 in HNSC. We analyzed ETV4 expression in HNSC patients’ data from the TCGA database, alongside clinical pathological characteristics. The STRING and GEPIA databases were utilized to explore ETV4’s interaction proteins and expression related genes. Gene Set Enrichment Analysis (GSEA) was performed on the stratified TCGA-HNSC cohort based on ETV4 expression levels. The correlation between ETV4 expression and immune cells, immune checkpoints, immune regulatory genes was further analyzed using R packages and TISIDB database. Finally, knockdown ETV4 in nasopharyngeal carcinoma cells (NPCs) using siRNA and evaluate cell proliferation, migration, and invasion using CCK-8, wound healing, clone formation, and Transwell assays. ETV4 was significantly overexpressed in HNSC and closely related with clinical pathological characteristics and prognosis. GSEA enrichment analysis showed significant enrichment of ETV4 in multiple immune suppression pathways. Further immune-related analysis indicated that ETV4 negatively correlated with most immune cells, immune checkpoints, tumor-infiltrating lymphocyte type characteristic molecules, immunoinhibitors, immune activators and MHC molecules. Knocking down ETV4 significantly inhibited the proliferation, migration and invasion of NPCs. ETV4 may serve as a prognostic biomarker and immunotherapy target in HNSC. High expression of ETV4 may have a negative regulatory effect on the immune level, matrix components and immune regulatory molecules.