Transcriptomic Analysis Reveals C-C Motif Chemokine Receptor 1 as a Critical Pathogenic Hub Linking Sjögren’s Syndrome and Periodontitis

TL;DR

This study identifies CCR1 as a key gene linking Sjögren’s syndrome and periodontitis through immune system disruptions.

Contribution

CCR1 is newly identified as a critical pathogenic hub connecting two diseases via immune infiltration.

Findings

Ninety-five common genes were found with similar expression trends in both diseases.

CCR1 was identified as the unique shared gene through LASSO modeling and showed predictive power.

Immune cell infiltration analysis showed CCR1's role in immune homeostasis disruption.

Abstract

Compelling evidence has demonstrated a bidirectional relationship between Sjögren’s syndrome (SS) and periodontitis (PD). Nevertheless, the underlying mechanisms driving their co-occurrence remain unclear, highlighting the need for finding the hub gene. This study sought to examine the common genes and any connections between SS and PD. Differently expressed genes (DEGs) were analyzed by means of gene set enrichment analysis (GSEA), weighted gene co-expression network analysis (WGCNA), and least absolute shrinkage and selection operator (LASSO) methods. The test and validation sets were used to depict the receiver operating characteristic (ROC) curves. The immune cell infiltration was performed via the cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) methodology. The relationships between immune infiltrating cells and the common gene were examined. Ninety-five common genes with similar expression trends were obtained after DEGs analysis, which were enriched in cytokine—cytokine receptor interaction, chemokine signaling pathway, proteasome, intestinal immune network for IgA production, and cytosolic DNA sensing pathway. Thirty-nine common genes were obtained after WGCNA. Sixteen shared genes of DEGs analysis and WGCNA were incorporated into the LASSO model to obtain the unique shared gene, C-C motif chemokine receptor 1 (CCR1), which overexpressed and owned predictable ROC curves in test and validation sets. The examination of immune cell infiltration underscored its crucial roles in the disturbance of immune homeostasis and the emergence of pathogenic circumstances with the simultaneous occurrence of SS and PD. CCR1 overexpresses and serves as a critical pathogenic hub linking SS and PD, which may play a role through immune cell infiltration.

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