Objective:
Oral cancer is one of the most common malignant tumors in the head and neck. It is easy to relapse and the prognosis is poor. However, the molecular mechanism in the development of oral cancer is still unclear.
Methods:
A total of 30 normal individuals and 30 patients with head and neck cancer who underwent surgery were recruited in the Fourth Hospital of Hebei Medical University between February 2019 and November 2021. And Human Protein Atlas (HPA) analysis, real time quantitative polymerase chain reaction (RT-qPCR) and immunofluorescence were used to verify the expression of SRY-Box Transcription Factor 9 (SOX9) and interleukin 1 A (IL1A). The GSE69002 dataset was downloaded from the gene expression omnibus (GEO) database. GEO2R was used to identify the differently expressed genes (DEGs). The protein-protein interaction (PPI) network was constructed by using the search tool for the retrieval of interacting genes/proteins (STRING), and Cytoscape software was performed for visualization. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) for enrichment analysis was made via the Database for Annotation Visualization and Integrated Discovery (DAVID), Metascape, Gene Set Enrichment Analysis (GSEA), and Bin Gene Ontology (BINGO) analysis. Gene Expression Profiling Interactive Analysis (GEPIA) analysis was used to analyze the expression level of hub genes and pathological stage. The cBioPortal can be used for mutation analysis and pathway prediction of hub genes. Kaplan Meier Plotter was used for survival analysis of hub genes.
Results:
The relative expression level of SOX9 (P=0.021, t=4.332) and IL1A (P=0.011, t= -4.213) in oral cancer was significantly higher than that in normal group. The DEGs mainly enriched in the cell division, inflammation, interleukin-12 beta subunit binding, interleukin-10 receptor binding. All the differentially expressed gene pathways eventually converge in cell growth and apoptosis. No relationships between the pathologic stage and expression of hub genes. The poor overall survival of patients with the high expression of SOX9 [hazard ratio (HR) = 1.46, P = 0.009] and IL1A (HR = 1.49, P = 0.008); There were strong correlations between the hub genes and the head and neck neoplasms via the comparative toxicogenomics database (CTD). The PCR results showed that the level of SOX9 (P<0.001, t = -23.368) in the cancer group was significantly higher than that in the normal group; The level of IL1A in cancer group was significantly higher than that in normal group (P<0.001, t = -11.960). Furthermore, the expression levels of SOX9 and IL1A were verified by the immunofluorescence assay.
Conclusion:
SOX9 and IL1A genes are highly expressed in oral cancer and might be potential therapeutic targets for oral cancer. The poor overall survival of patients with the high expression of SOX9 and IL1A.
