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. 2025 Jun 20;20(6):e0324007.
doi: 10.1371/journal.pone.0324007. eCollection 2025.

Uncovering common disease mechanisms and critical biomarkers in Crohn's disease with concurrent psoriasis and exploring potential therapeutic agents

Tianqi Liu  1 , Xiaoqing Zhang  2 , Ruiqi Chen  1 , Yifan Sun  1 , Ruijian Zhang  1 , Liwen Zhang  1 , Zhepeng Luo  1 , Jiani Wang  1
Affiliations

Uncovering common disease mechanisms and critical biomarkers in Crohn's disease with concurrent psoriasis and exploring potential therapeutic agents

Tianqi Liu et al. PLoS One. .

Abstract

Introduction: Research findings show a substantial correlation between Crohn's disease and psoriasis. However, the exact cause or pathogenesis of the concurrent manifestations of these two conditions in the same individuals remains uncertain. This research aimed to scrutinize the important molecules and mechanisms responsible for the concomitance of Crohn's disease and Psoriasis by using quantitative bioinformatics utilizing a publicly available RNA sequencing repository.

Methods: The database Gene Expression Omnibus were assessed, specifically for Crohn's disease (GSE95095) and psoriasis (GSE13355). The 'limma' library of the R programming syntax is employed to identify differentially expressed genes. The Search Tool for Interacting Genes dataset was utilized to study the interaction between proteins networks. The Cytoscape software was utilized to efficiently view and analyse these Protein-Protein Interaction networks. The ctoHubba Cytoscape plugin helps in the selection of hub genes. These hub genes have been confirmed using data from GSE102133 for Crohn's disease and GSE14905 for psoriasis. The ROC curves were utilized in this study to assess the diagnostic value of the hub genes. Moreover, new research involving gene-set enriched studies and the study of immunological surveillance associated with these specific genes is attainable.

Results: Among the identified common DEGs, 40 genes were downregulated and 37 were upregulated, totaling 77 genes. Crohn's disease and Psoriasis had a higher concentration of pathways associated with inflammation. After validation, functionality of hub genes was confirmed for S100A12, CXCL8, IL1RN, S100A9, CXCL10, MMP1, CXCL1, FPR1, CXCR2, and S100A8. The hub genes showed an increase in expression in response to neutrophil infiltration. The expression of S100A12, CXCL8, IL1RN, S100A9, CXCL10, MMP1, CXCL1, FPR1, CXCR2, and S100A8 was found to be significantly linked to immune processes such as neutrophil activation, neutrophil chemotaxis, and neutrophil migration associated with Crohn's and Psoriasis disease.

Conclusions: This bioinformatics study has elucidated S100A12, CXCL8, IL1RN, S100A9, CXCL10, MMP1, CXCL1, FPR1, CXCR2, and S100A8 as the central genes in the pathogenesis of CD and Psoriasis comorbidity. The significance of neutrophil infiltration in promoting inflammatory and immune-mediated dysfunction seems to be crucial in the etiology of concurrent Crohn's and Psoriasis, offering an avenue for diagnostic and therapeutic methods.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Identification of differentially expressed genes.
(A) The volcano map of GSE95095. (B) The volcano map of GSE13355; upregulated genes are marked in red; downregulated genes are marked in blue. (C) The two datasets showed an overlap of 37 upregulated DEGs. (D) The two datasets showed an overlap of 40 downregulated DEGs.
Fig 2
Fig 2. The enrichment analysis results of co-DEGs.
The enrichment analysis results of GO (A) and KEGG (B) pathway.
Fig 3
Fig 3. the PPI Network for co-DEGs.
(A) PPI network of the common DEGs constructed by STRING. (B) PPI network of the DEGs constructed by Cytoscape. (C,D) Two gene clustering modules constructed by the MCODE plug-in. (E) Identification of 14 hub genes for hub genes by five algorithms.
Fig 4
Fig 4. Validation of hub genes in the diagnostic value.
Fig 5
Fig 5. The PPI and Immune Infiltration of Hub Genes.
(A) Hub genes and their co-expression genes were analyzed via GeneMANIA. (B) Association between the hub genes and immune infiltration in GSE95095. (B) Association between the hub genes and immune infiltration in GSE13355.
Fig 6
Fig 6. The enrichment analysis of the hub genes.
(A) GO enrichment analysis of the hub genes. (B) A merged enrichment plot of ten hub genes from gene set enrichment analysis in GSE95095. (C) A merged enrichment plot of ten hub genes from gene set enrichment analysis in GSE13355.
Fig 7
Fig 7. The interaction networks of gene-TF and gene-miRNAs.
(A) TF-mRNA network of hub genes; (B) miRNA - mRNA network of hub genes.
See this image and copyright information in PMC

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