The potential crosstalk genes and molecular mechanisms between intracranial aneurysm and periodontitis

Background:The risk of intracranial aneurysm (IAs) development and rupture is significantly higher in patients with periodontitis (PD), suggesting an association between the two. However, the specific mechanisms of association between these two diseases have not been fully investigated. The aim of this study was to investigate potential crosstalk genes, pathways between IAs and PD.Methods:We downloaded IAs and PD data from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were identified, and functional enrichment analysis was performed on these overlapping DEGs. The protein-protein interaction (PPI) network was constructed and the cytoHubba plugin was used to identify PPI key genes. Next, weighted gene co-expression network analysis (WGCNA) was performed. Subsequently, we validated the key crosstalk genes in 2 independent external datasets. In addition, the immune cell landscape was assessed and the correlation of key crosstalk genes with each immune cell was calculated. Finally, transcription factors (TFs) regulating key crosstalk genes were explored and their expression levels were further validated in the full dataset.Results:127 overlapping DEGs were identified and functional enrichment analysis highlighted the important role of immune reflection in the pathogenesis. We identified ITGAX and COL4A2 as key crosstalk genes and the expression levels of them were significantly elevated in the test dataset and external validation dataset. In addition, the expression of multiple immune cells was significantly elevated in PDs and IAs compared to controls, and both key crosstalk genes were significantly negatively associated with Macrophages M2. Finally, GATA2 was identified as a potential key transcription factor (TF), which regulates two key crosstalk genes and was upregulated in expression in the full dataset.Conclusion:The present study identifies key crosstalk genes and TF in IAs and PD, providing new insights for further study of the co-pathogenesis of IAs and PD from an immune and inflammatory perspective.

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