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Published on: February 3, 2017
Identification and cross-validation of autophagy-related genes in cardioembolic stroke
Yufang Yang1, Min Zhang2, Ziqing Li1
1School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Insights
Cardioembolic stroke (CE stroke) involves autophagy. Bioinformatics identified 41 autophagy-related genes, including SERPINA1 and CXCR4, offering potential therapeutic targets for CE stroke treatment.
Area of Science:
- Biomedical research
- Genomics
- Molecular biology
Background:
- Cardioembolic stroke (CE stroke) is a severe subtype of ischemic stroke with high recurrence and fatality rates.
- The underlying pathogenesis of CE stroke is not fully understood, though autophagy is implicated.
- Identifying molecular markers and therapeutic targets is crucial for improving CE stroke outcomes.
Purpose of the Study:
- To identify potential autophagy-related molecular markers for CE stroke using bioinformatics.
- To uncover potential therapeutic targets for CE stroke based on autophagy-related gene expression.
- To elucidate the role of autophagy in the development of CE stroke.
Main Methods:
- Utilized the GSE58294 mRNA expression dataset from the GEO database.
- Screened for autophagy-related differentially expressed (DE) genes in CE stroke using R software.
- Performed protein-protein interaction (PPI), correlation, and Gene Ontology (GO) enrichment analyses.
- Verified DE genes using datasets GSE66724, GSE41177, and GSE22255 with Student's t-test.
Main Results:
- Identified 41 autophagy-related DE genes (37 upregulated, 4 downregulated) between CE stroke patients and healthy controls.
- GO and KEGG enrichment analyses revealed terms related to autophagy, apoptosis, and ER stress.
- Discovered hub genes, including CXCR4 (general stroke) and specific CE stroke genes like ARNT, MAPK1, ATG12, ATG16L2, ATG2B, and BECN1.
Conclusions:
- Identified 41 autophagy-related genes as potential biomarkers for CE stroke.
- SERPINA1, WDFY3, ERN1, RHEB, and BCL2L1 are significant DE genes potentially regulating CE stroke via autophagy.
- The findings provide insights into autophagy's role in CE stroke and suggest novel therapeutic targets.
Objective:
Cardioembolic stroke (CE stroke, also known as cardiogenic cerebral embolism, CCE) has the highest recurrence rate and fatality rate among all subtypes of ischemic stroke, the pathogenesis of which was unclear. Autophagy plays an essential role in the development of CE stroke. We aim to identify the potential autophagy-related molecular markers of CE stroke and uncover the potential therapeutic targets through bioinformatics analysis.
Methods:
The mRNA expression profile dataset GSE58294 was obtained from the GEO database. The potential autophagy-related differentially expressed (DE) genes of CE stroke were screened by R software. Protein-protein interactions (PPIs), correlation analysis, and gene ontology (GO) enrichment analysis were applied to the autophagy-related DE genes. GSE66724, GSE41177, and GSE22255 were introduced for the verification of the autophagy-related DE genes in CE stroke, and the differences in values were re-calculated by Student's t-test.
Results:
A total of 41 autophagy-related DE genes (37 upregulated genes and four downregulated genes) were identified between 23 cardioembolic stroke patients (≤3 h, prior to treatment) and 23 healthy controls. The KEGG and GO enrichment analysis of autophagy-related DE genes indicated several enriched terms related to autophagy, apoptosis, and ER stress. The PPI results demonstrated the interactions between these autophagy-related genes. Moreover, several hub genes, especially for CE stroke, were identified and re-calculated by Student's t-test.
Conclusion:
We identified 41 potential autophagy-related genes associated with CE stroke through bioinformatics analysis. SERPINA1, WDFY3, ERN1, RHEB, and BCL2L1 were identified as the most significant DE genes that may affect the development of CE stroke by regulating autophagy. CXCR4 was identified as a hub gene of all types of strokes. ARNT, MAPK1, ATG12, ATG16L2, ATG2B, and BECN1 were identified as particular hub genes for CE stroke. These results may provide insight into the role of autophagy in CE stroke and contribute to the discovery of potential therapeutic targets for CE stroke treatment.
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