HOXC6 overexpression stimulates cell migration and correlates with poor prognosis in head and neck squamous cell carcinoma

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and accounts for 2% of cancer-related deaths. Although the oncogenic role of HOXC6 in solid tumors is known, its functional relevance in HNSCC remains elusive. Using The Cancer Genome Atlas (TCGA, with 520 HNSCC samples) data and in vitro models, we investigated the functional role of HOXC6 in HNSCC. TCGA analysis revealed that HOXC6 overexpression in HNSCC tissues correlated with malignant progression and poor survival outcomes. In vitro studies confirmed HOXC6 overexpression in HNSCC cell lines, and knockdown of HOXC6 significantly reduced both cell proliferation and migration, highlighting the oncogenic role of HOXC6. Additionally, pathway analysis of RNA-seq data linked HOXC6 expression with immune evasion and dysregulation of cell cycle genes, particularly the E2F and G2M checkpoints. Furthermore, H3K27ac ChIP-seq data showed that histone acetylation at the HOXC6 promoter drives HOXC6 overexpression. This study identified HOXC6 as a key oncogenic driver in HNSCC and as a candidate biomarker for HNSCC. Targeting HOXC6 could pave the way for improved biomarker-driven approaches in HNSCC treatment to reduce recurrence and improve patient survival rates.