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Updated: May 9, 2025
Isolation and Flow Cytometric Analysis of Immune Cells from the Ischemic Mouse Brain
Published on: February 12, 2016
Shared circulating diagnostic biomarkers and molecular mechanisms in ischemic stroke and systemic lupus erythematosus
Xiaoyi Ma1, Lifei Huang2, Huanhuan Yan3,4
1Department of Geriatrics, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
Insights
This study identified shared driver genes and diagnostic biomarkers, EIF2AK2, PARP9, and IFI27, for ischemic stroke and systemic lupus erythematosus (SLE). Findings suggest common molecular mechanisms and immune cell infiltration, paving the way for new therapeutic strategies.
Area of Science:
- Neuroscience
- Immunology
- Genetics
Background:
- Ischemic stroke and systemic lupus erythematosus (SLE) are complex diseases with suspected shared genetic and etiological factors.
- Identifying common molecular mechanisms and diagnostic biomarkers could improve understanding and treatment for both conditions.
Purpose of the Study:
- To identify shared diagnostic biomarkers and molecular mechanisms between ischemic stroke and SLE.
- To analyze publicly available gene expression datasets to find commonalities.
Main Methods:
- Differential gene expression analysis using limma.
- Weighted Gene Coexpression Network Analysis (WGCNA) to identify co-expression modules.
- LASSO regression for biomarker selection and pathway enrichment analysis (GO, KEGG).
- Immune cell infiltration analysis using CIBERSORT and validation in an MCAO mouse model.
Main Results:
- Identified 69 shared driver genes, narrowed to 10 hub genes via Protein-Protein Interaction network analysis.
- Selected EIF2AK2, PARP9, and IFI27 as significant diagnostic biomarkers using LASSO regression and ROC analysis.
- Observed nearly identical immune cell infiltration profiles in both diseases.
- Validated elevated expression of hub genes in an MCAO mouse model.
Conclusions:
- EIF2AK2, PARP9, and IFI27 are potential shared diagnostic biomarkers for ischemic stroke and SLE.
- Common molecular mechanisms, particularly immune cell infiltration, are implicated in both diseases.
- These findings offer insights for developing targeted therapies for shared disease pathways.
Introduction:
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.
Methods:
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.
Results:
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.
Discussion:
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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