Abstract
Background/Objectives: Oral squamous cell carcinoma (OSCC) is the most prevalent malignancy of the oral cavity and is frequently diagnosed at an advanced stage, resulting in poor prognosis and limited treatment options. Identifying reliable biomarkers that can predict tumor progression and serve as therapeutic targets remains an urgent clinical need. Methods: To identify key molecular drivers in OSCC, we performed an integrative bioinformatics analysis of five OSCC-related microarray datasets from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were identified and subjected to functional enrichment, protein-protein interaction (PPI) network construction, and hub gene ranking using Cytoscape. Candidate genes were further validated using TCGA, UALCAN, and the Human Protein Atlas. In vitro functional assays were performed to evaluate the effect of TK1 knockdown on cell migration. Results: A total of 138 common DEGs were identified across datasets. GO enrichment revealed that these genes were associated with cell proliferation, extracellular matrix organization, and metastasis-related processes. Thymidine kinase 1 (TK1) was identified as a key hub gene and found to be consistently overexpressed in OSCC tissues. Kaplan-Meier analysis showed that high TK1 expression correlated with poor overall survival in head and neck cancer. TK1 knockdown in OSCC cell lines significantly impaired cell migration and wound-healing ability. Conclusions: Our findings suggest that TK1 plays an active role in promoting OSCC progression and may serve as a prognostic biomarker and potential therapeutic target for metastatic OSCC.