Identification and Validation of Hub Genes Associated With Periodontitis and Systemic Lupus Erythematosus
Yafang Li, Xin Xu, Zhijing Wu, Feng Li, Jie ZhangABSTRACT
Background
Accumulating evidence suggests a close relationship between periodontitis and systemic lupus erythematosus (SLE); however, the shared molecular mechanisms underlying this association remain unclear. This study aimed to identify candidate genes and molecular features shared between periodontitis and SLE through integrative bioinformatics analysis and clinical validation.
Methods
Gene expression profiles were obtained from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) shared between periodontitis and SLE were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed, followed by protein–protein interaction (PPI) network construction and hub gene screening. The expression patterns of the hub genes were evaluated in independent validation datasets, and their discriminatory performance was assessed by receiver operating characteristic (ROC) curve analysis. Immune cell infiltration and its correlations with hub gene expression were further investigated. Transcription factor–microRNA regulatory networks and candidate compounds were computationally predicted. Finally, quantitative real‐time PCR (qPCR) was performed to validate hub gene expression in clinical samples.
Results
A total of 124 overlapping DEGs were identified, from which five hub genes—CCL3, LY96, FOS, MMP9, and PTGS2—were selected. GO and KEGG enrichment analyses indicated that the overlapping DEGs were predominantly associated with inflammatory and immune‐related biological processes and signaling pathways. All five hub genes showed consistent expression patterns in the independent periodontitis validation dataset, whereas FOS, LY96, and PTGS2, but not CCL3 and MMP9, showed consistent differential expression in the independent SLE validation dataset. ROC analyses demonstrated varying discriminatory performance across the analyzed datasets. Immune infiltration analysis revealed differences in estimated immune cell profiles in both disease datasets, and computational prediction identified candidate regulatory interactions and compounds for further investigation. qPCR validation in clinical samples ( n = 15 per group) showed significantly increased expression of all five hub genes in gingival tissues from patients with periodontitis and PBMCs from patients with SLE compared with their respective healthy controls.
Conclusion
This study identified CCL3, LY96, FOS, MMP9, and PTGS2 as candidate genes associated with periodontitis and SLE. FOS, LY96, and PTGS2 showed consistent expression patterns across datasets, whereas CCL3 and MMP9 exhibited dataset‐dependent variation in SLE. Clinical qPCR validation showed increased expression of all five genes in both disease cohorts. These findings provide insight into the shared molecular features of periodontitis and SLE and warrant further validation in larger, independent, and clinically well‐characterized cohorts.