Identification of Shared Associated Genes and Potential Molecular Mechanisms Between Psoriasis and Ischemic Stroke Based on Bioinformatics, Machine Learning, and Molecular Dynamics Simulation.
TL;DR
Chronic inflammation and immune dysregulation may contribute to psoriasis and IS comorbidity and integrative analysis highlights TLR2 and TNFSF10 as potential mechanistic candidates associated with persistent immune activation, endothelial dysfunction, and vascular injury.
Abstract
INTRODUCTION/
Objective
Psoriasis is associated with an increased risk of Ischemic Stroke (IS), but the underlying mechanisms remain unclear. This study aims to identify shared associated genes and explore potential mechanisms underlying psoriasis and IS.
Methods
Gene expression datasets from the GEO database were analyzed to identify common Differentially Expressed Genes (co-DEGs). Integrative bioinformatics analyses, machine-learning algorithms, single-cell RNA sequencing, molecular docking, and molecular dynamics simulations were employed to identify candidate shared genes and investigate the potential molecular mechanisms.
Results
We identified 57 co-DEGs shared between psoriasis and IS. Enrichment analyses indicated that these genes were mainly associated with immune and inflammatory pathways, including NET formation, NF-κB, TLR, and IL-17 signaling pathways. TLR2 and TNFSF10 were identified as shared associated genes and remained significant across leave-one-out sensitivity analyses, demonstrating the robustness of their differential expression. Single-cell analysis revealed that TLR2 and TNFSF10 were mainly expressed in macrophages, NK cells, and smooth muscle cells. Epigallocatechin gallate was identified as a candidate compound for further investigation.
Discussion
Our integrative analysis highlights TLR2 and TNFSF10 as potential mechanistic candidates associated with persistent immune activation, endothelial dysfunction, and vascular injury. These genes may participate in interconnected inflammatory processes involving TLR, IL-17, NF-κB, and NET-related pathways, providing a potential molecular link between psoriasis and IS.
Conclusion
Chronic inflammation and immune dysregulation may contribute to psoriasis and IS comorbidity. TLR2 and TNFSF10 were identified as shared associated genes. These findings provide exploratory insights into the immunoinflammatory mechanistic association between psoriasis and IS.