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

被引:12
作者
Chen, Xin [1 ,2 ,3 ]
Lei, Hao [4 ]
Cheng, Yuxun [1 ,2 ,3 ]
Fang, Shishu [1 ,2 ,3 ]
Sun, Weifu [1 ,2 ,3 ]
Zhang, Xiaochen [1 ,2 ,3 ]
Jin, Zuolin [1 ,2 ,3 ,5 ,6 ,7 ]
机构
[1] Air Force Med Univ, Sch Stomatol, Dept Orthodont, State Key Lab Mil Stomatol, Xian, Peoples R China
[2] Air Force Med Univ, Natl Clin Res Ctr Oral Dis, Sch Stomatol, Xian, Peoples R China
[3] Air Force Med Univ, Shaanxi Clin Res Ctr Oral Dis, Sch Stomatol, Dept Orthodont, Xian, Peoples R China
[4] Xi An Jiao Tong Univ, Affiliated Hosp 1, Sch Med, Dept Dermatol, Xian, Peoples R China
[5] Air Force Med Univ, Sch Stomatol, Dept Orthodont, State Key Lab Mil Stomatol, Xian 710032, Peoples R China
[6] Air Force Med Univ, Natl Clin Res Ctr Oral Dis, Sch Stomatol, Xian 710032, Peoples R China
[7] Air Force Med Univ, Shaanxi Clin Res Ctr Oral Dis, Sch Stomatol, Dept Orthodont, Xian 710032, Peoples R China
基金
中国国家自然科学基金;
关键词
bioinformatics analysis; comorbidity; oral squamous cell carcinoma; periodontitis; FUSOBACTERIUM-NUCLEATUM; GENE POLYMORPHISMS; EPITHELIAL-CELLS; CANCER; MATRIX; EXPRESSION; MICROBIOTA; HEAD; BETA;
D O I
10.1111/odi.14419
中图分类号
R78 [口腔科学];
学科分类号
1003 ;
摘要
ObjectiveTo analysis the relationship between periodontitis (PD) and oral squamous cell carcinoma (OSCC) by bioinformatic analysis. Materials and MethodsWe 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. ResultsWe identified 31 DEGs (16 up-regulated and 15 down-regulated). Four hub genes were obtained by qRT-PCR and validation dataset analysis, including IL-1 beta, 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. ConclusionsWe identified 4 hub genes between PD and OSCC, including IL-1 beta, 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.
引用
收藏
页码:390 / 407
页数:18
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