Abstract
BACKGROUND: Clinically, psoriasis (PSO) and ulcerative colitis (UC) coexisted in some patients. However, the molecular pathogenesis of PSO and UC coexistence remains unclear. This study aimed at exploring the risk genes based on bioinformatics analyses, contributing to the pathogenesis of both diseases. METHODS: Gene expression data sets GSE14905 of PSO and GSE87466 of UC were used to screen the differential expression genes (DEGs) shared by these 2 diseases. The potential biological functions and pathways of these DEGs were analyzed to construct protein-protein interaction network, identify hub genes and transcription factor (TF) for the development of a TF-mRNA regulatory network. Finally, the expression of top hub genes was validated in GSE13355 (PSO) and GSE59071 (UC), as well as clinical specimens, using quantitative real-time polymerase chain reaction (qRT-PCR), immunohistochemistry and immunofluorescence. RESULTS: Bioinformatics analyses identified 30 DEGs shared by both PSO and UC (|log fold change|>2.0 and P < .05), primarily enriched in the activation of immune cells and chemokine-chemokine receptor interaction. Furthermore, protein-protein interaction and TF-mRNA regulatory networks pinpointed 9 core genes and 6 TFs. In addition, experimental validation via qRT-PCR confirmed elevated expression of STAT1 (P < .0001), with immunofluorescence showed that concentrated STAT1 expression in CD68 + macrophages in the PSO and UC lesions. Finally, qRT-PCR detected up-regulated CXCL1 (P < .01), CCL20 (P < .01), and matrix metalloproteinase9 (P < .001) expression compared with healthy skin controls, and results of immunohistochemistry of lesional tissue were consistent with the trend. CONCLUSION: PSO and UC share chemokine abnormalities, including elevated levels of CCL20, CXCL1, and matrix metalloproteinase9, potentially linked to STAT1-expressing CD68 + macrophage infiltration. These shared molecular features suggest their potential as biomarkers for co-morbidity risk.