Exploration of the shared gene signatures and potential molecular mechanisms between Crohn's disease and psoriasis.

OBJECTIVE

Crohn's disease (CD) and psoriasis are both chronic inflammatory diseases. However, the exact molecular interplay remains incompletely elucidated. This study aimed to identify shared molecular markers and functional pathways underlying both diseases and explore their correlations with immune infiltration.

METHODS

We analyzed microarray datasets (GSE30999, GSE186582) from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs). Weighted Gene Co-expression Network Analysis (WGCNA) was used to construct co-expression modules, followed by GO and KEGG enrichment analysis. Hub genes were selected via support vector machine recursive feature elimination (SVM-RFE) and validated in independent datasets (GSE14905, GSE112366). Immune infiltration was evaluated by CIBERSORT.

RESULTS

We identified 1540 DEGs in CD and 1157 in psoriasis, with 234 overlapping DEGs enriched in the IL-17 signaling pathway (KEGG) and, critically, in secretory granule/cytoplasmic vesicular lumen (GO-CC); these cellular compartments are essential for the production and release of pro-inflammatory cytokines downstream of IL-17 signaling. SVM-RFE identified three hub genes (CLDN8, APOL1, TCN1) validated in independent datasets. In CD, APOL1/TCN1 correlated positively with Neutrophils and inversely with M2 Macrophages, while CLDN8 showed the opposite. In psoriasis, APOL1/TCN1 correlated positively with Activated CD4 Memory T cells and inversely with Resting Mast cells, whereas CLDN8 displayed the opposite.

CONCLUSION

This study elucidated the shared expression markers and functional pathways between CD and psoriasis. These findings offer new clues for comorbid mechanisms and potential therapeutic targets, needing further validation. Key points • The study uncovers shared gene signatures and functional pathways between CD and psoriasis. • Three hub genes (CLDN8, APOL1, TCN1) and IL-17 signaling pathway were validated as potential diagnostic or therapeutic targets for both CD and psoriasis through integrative bioinformatics.