Oral squamous cell carcinoma (OSCC) is the most common malignant tumor of the oral cavity. Although the molecular mechanisms of OSCC have been explored, they remain incompletely understood. This study aimed to comprehensively analyze key molecular pathways involved in the occurrence and progression of OSCC, with the goal of identifying novel biomarkers for early diagnosis and potential therapeutic targets to improve patient prognosis.

OSCC datasets (GSE31056 and GSE51010) were obtained from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were identified and subjected to functional enrichment analysis, weighted gene co-expression network analysis (WGCNA), and protein-protein interaction (PPI) network analysis to predict core genes. Immune infiltration analysis was performed to estimate immune cell proportions. The Comparative Toxicogenomics Database (CTD) was used to identify diseases associated with the core genes. Real-time quantitative polymerase chain reaction (RT-qPCR) was conducted to validate the expression levels of core genes and related proteins.

A total of 1017 DEGs were identified, which were mainly enriched in metabolic pathways, as well as the p53 and PPAR signaling pathways. Integration of three algorithms identified four central genes: BUB1, CCNB2, KIF23, and NEK2. Among them, BUB1 and CCNB2 were significantly overexpressed in OSCC compared with normal tissue samples. CTD analysis linked these genes to oral tumors, inflammation, and immune system diseases. Immune infiltration analysis revealed a higher proportion of neutrophils in OSCC samples. RT-qPCR confirmed elevated expression of BUB1, CCNB2, KIF23, NEK2, BAX, and Caspase-3 in OSCC.

Overexpression of BUB1 and CCNB2 may enhance cell cycle activity and inflammatory responses, thereby promoting OSCC cell proliferation.