Abstract
BackgroundIschemic Stroke (IS) is a major disease which greatly threatens human health. Recent studies showed sex-specific outcomes and mechanisms of cerebral ischemic stroke. This study aimed to identify the key changes of gene expression between male and female IS in humans.MethodsGene expression dataset GSE22255, including peripheral blood samples, was downloaded from the Gene Expression Omnibus (GEO) dataset. Differentially Expressed Genes (DEGs) with a LogFC>1, and a P-value <0.05 were screened by BioConductor R package and grouped in female, male and overlap DEGs for further bioinformatic analysis. Gene Ontology (GO) functional annotation, Protein-Protein Interaction (PPI) network, “Molecular Complex Detection” (MCODE) modules, CytoNCA (cytoscape network centrality analysis) essential genes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway interrelation analysis were performed.ResultsIn a total of 54,665 genes, 185 (73 ups and 112 downs) DEGs in the female dataset, 461 DEGs (297 ups and 164 downs) in the male dataset, within which 118 DEGs overlapped (7 similar changes in female and male, 111 opposite changes in female and male) were obtained from the GSE22255 dataset. Female, male and overlapping DEGs enriched for similar cellular components and molecular function. Male DEGs enriched for divergent biological processes from female and overlapping DEGs. Sex-specific and overlapping DEGs were put into the PPI network. Overlapping genes such as IL6, presented opposite changes and were mainly involved in cytokine-cytokine receptor interactions, the TNF-signalling pathway, etc.ConclusionThe analysis of sex-specific DEGs from GEO human blood samples showed that not only specific but also opposite DEG alterations in the female and male stroke genome wide dataset. The results provided an overview of sex-specific mechanisms, which might provide insight into stroke and its biomarkers and lead to sex-specific prognosis and treatment strategies in future clinical practice.
Highlights
Stroke is the leading cause of disability and the second leading cause of death worldwide, with an annual incidence of approximately 17 million
Male and overlapping Differentially Expressed Genes (DEGs) enriched for similar cellular components and molecular function
The results provided an overview of sex-specific mechanisms, which might provide insight into stroke and its biomarkers and lead to sex-specific prognosis and treatment strategies in future clinical practice
Summary
Stroke is the leading cause of disability and the second leading cause of death worldwide, with an annual incidence of approximately 17 million. Sex differences were seen for IS as females had higher incidence and longer life expectancy but worse functional outcomes [3,4], which might be due to different risk factors [5,6,7], anatomic structural Willis incompletion or white integrity [8,9], biologically inherent sex chromosome complemented with gonadal hormones [10,11,12], socialized reasons of in-hospital care [6,13], and pathology and treatment [14,15]. Animal-based research has observed decreased infarct size and improved outcomes in female compared to males [16]. Many studies have observed sex differences in IS; the mechanism has yet to be elucidated
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