Shared circulating diagnostic biomarkers and molecular mechanisms in ischemic stroke and systemic lupus erythematosus

TL;DR

This study finds shared genes and immune patterns between stroke and lupus, suggesting common causes and possible new treatments.

Contribution

Identifies shared diagnostic biomarkers and immune mechanisms between ischemic stroke and SLE using multi-omics analysis.

Findings

69 shared driver genes were identified between ischemic stroke and SLE.

Three hub genes (EIF2AK2, PARP9, IFI27) were validated as potential diagnostic biomarkers.

Immune cell infiltration profiles were nearly identical in both diseases.

Abstract

Ischemic stroke, a prevalent cerebrovascular disorder characterized by reduced cerebral blood flow, and systemic lupus erythematosus (SLE), an autoimmune disease affecting various organs, are suspected to share overlapping etiological mechanisms and genetic predispositions. This study aimed to identify shared diagnostic biomarkers and molecular mechanisms by analyzing datasets from the GEO database.

We pinpointed differentially expressed genes using the limma package and identified co-expression modules associated with both conditions using Weighted Gene Coexpression Network Analysis. Pathway enrichment analysis was conducted using GO and KEGG to identify co-driver genes. LASSO regression was applied to evaluate potential diagnostic markers, and immune cell infiltration was quantified using the CIBERSORT computational method. A middle cerebral artery occlusion (MCAO) mouse model was developed to assess core gene expression in vivo.

We identified 69 shared driver genes linked to stroke and SLE, which were narrowed down to the top 10 genes through a Protein-Protein Interaction network analysis with Cytoscape. LASSO regression selected EIF2AK2, PARP9, and IFI27 as diagnostic biomarkers, supported by ROC curve analysis. Immune cell infiltration profiles were nearly identical between ischemic stroke and SLE. 9.4T MR imaging, H&E and Nissl staining confirmed ischemic stroke in the MCAO model, and qPCR analysis confirmed elevated expression of the three hub genes.

Our findings provide evidence for common diagnostic indicators and disease mechanisms in ischemic stroke and SLE, offering novel insights for potential therapeutic strategies targeting their shared immune cell infiltration microenvironments.

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