基于生物信息学方法探讨基质金属蛋白酶-13 通过 TNF 信号通路对舌鳞状细胞癌恶性生物学行为的影响

Identification of the etiology, molecular mechanisms, and carcinogenic pathways of tongue squamous cell carcinoma (TSCC) is crucial for developing new diagnostic and therapeutic strategies. This study used bioinformatics methods to identify key genes in TSCC and explored the potential functions and pathway mechanisms related to the malignant biological behavior of TSCC.

Gene chip data sets (i.e., GSE13601 and GSE34106) containing the data of both TSCC patients and normal control subjects were selected from the Gene Expression Omnibus (GEO) database. Using a gene expression analysis tool (GEO2R) of the GEO database, the differentially expressed genes (DEGs) were identified using the following criteria: |log fold change| >1, and P<0.05. The GEO2R tool was also used to select the upregulated DEGs in the chip candidates based on a P value <0.05. A Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, Gene Ontology (GO) function analysis, and a protein-protein interaction (PPI) network analysis were then conducted. The results were displayed using R language packages, including volcano plots, Venn diagrams, heatmaps, and enriched pathway bubble charts. Genes from the MalaCards database were compared with the candidate genes, and a thorough review of the literature was conducted to determine the clinical significance of these genes. Finally, feature gene-directed chemical drugs or targeted drugs were predicted using the Comparative Toxicogenomics Database (CTD).

In total, 767 upregulated DEGs were identified from GSE13601 and 695 from GSE34106. By intersecting the upregulated DEGs from both data sets using a Venn diagram, 100 DEGs related to TSCC were identified. The enrichment analysis of the KEGG signaling pathways identified the majority of the pathways associated with the upregulated DEGs, including the Toll-like receptor signaling pathway, the extracellular matrix-receptor interaction, the tumor necrosis factor (TNF) signaling pathway, cytokine-cytokine receptor interaction, the chemokine signaling pathway, the interlukin-17 signaling pathway, and natural killer cell-mediated cytotoxicity. The PPI network and module analyses of the shared DEGs ultimately resulted in five clusters and 55 candidate genes. A further intersection analysis of the TSCC-related genes in the MalaCards database via a Venn diagram identified three important shared DEGs; that is, matrix metalloproteinase-1 ( MMP1 ), MMP9 , and MMP13 . In the CTD, seven drugs related to MMP13 were identified for treating tongue tumors.

This study identified key genes and signaling pathways involved in TSCC and thus extended understandings of the molecular mechanisms that underlie the development and progression of TSCC. Additionally, this study showed that MMP13 may influence the malignant biological behavior of TSCC through the TNF signaling pathway. This finding could provide a theoretical basis for research into early differential diagnosis and targeted treatment.