CXCL8, MMP12, and MMP13 are common biomarkers of periodontitis and oral squamous cell carcinoma.

ABSTRACT

OBJECTIVE: To analysis the relationship between periodontitis (PD) and oral squamous cell carcinoma (OSCC) by bioinformatic analysis. MATERIALS AND METHODS: We analyzed the gene expression profiles of PD (GSE16134) from the Gene Expression Omnibus (GEO) database and OSCC samples from TCGA-HNSC (head and neck squamous cell carcinoma) and identified common differentially expressed genes (DEGs) in PD and OSCC. Then, functional annotation and signaling pathway enrichment, protein interaction network construction, and hub gene identification were performed. Subsequently, the function and signaling pathway enrichment of hub genes, miRNA interaction, and transcription factor interaction analyses were carried out. We analyzed GSE10334 and GSE30784 as validation datasets, and performed qRT-PCR experiments simultaneously for validation, and obtained 4 hub genes. Finally, immune infiltration analysis and clinical correlation analysis of 4 hub genes and related miRNAs were performed. RESULTS: We identified 31 DEGs (16 up-regulated and 15 down-regulated). Four hub genes were obtained by qRT-PCR and validation dataset analysis, including IL-1ß, CXCL8, MMP12, and MMP13. The expression levels of them were all significantly upregulated in both diseases. The functions of these genes focus on three areas neutrophil chemotaxis, migration, and CXCR chemokine receptor binding. Key pathways include IL-17 signaling pathway, chemokine signaling pathway, and cytokine-cytokine receptor interactions pathway. Immune infiltration analysis showed that the expressions of 4 hub genes were closely related to a variety of immune cells. ROC curve analysis indicated that AUCs of 4 hub genes are all greater than 0.7, among which MMP12 and MMP13 were greater than 0.9. Kaplan-Meier survival analysis indicated that worse OS was strongly correlated with CXCL8 and MMP13 high-expression groups. MMP12 low-expression group was strongly associated with worse OS. The results of multivariate Cox regression analysis showed that age, N stage, CXCL8, MMP12, and MMP13 were independent prognostic factors for OS. We also identified 3 miRNAs, including hsa-miR-19b-3p, hsa-miR-181b-2-3p, and hsa-miR-495-3p, that were closely related to 4 hub genes. Hsa-miR-495-3p is closely related to the diagnosis and prognosis of OSCC. CONCLUSIONS: We identified 4 hub genes between PD and OSCC, including IL-1ß, CXCL8, MMP12, and MMP13. These genes may mediate the co-morbid process of PD and OSCC through inflammation-related pathways such as the IL-17 signaling pathway. It is worth noting that CXCL8, MMP12, and MMP13 have great significance in the diagnosis and prognosis of OSCC.