Abstract
Ischemic stroke (IS) greatly threatens human health resulting in high mortality and substantial loss of function. Recent studies have shown that the outcome of IS has sex specific, but its mechanism is still unclear. This study is aimed at identifying the sexually dimorphic to peripheral immune response in IS progression, predicting potential prognostic biomarkers that can lead to sex-specific outcome, and revealing potential treatment targets. Gene expression dataset GSE37587, including 68 peripheral whole blood samples which were collected within 24 hours from known onset of symptom and again at 24-48 hours after onset (20 women and 14 men), was downloaded from the Gene Expression Omnibus (GEO) datasets. First, using Bioconductor R package, two kinds of differentially expressed genes (DEGs) (nonsex-specific- and sex-specific-DEGs) were screened by follow-up (24-48 hours) vs. baseline (24 hours). 30 nonsex-specific DEGs (1 upregulated and 29 downregulated), 79 female-specific DEGs (25 upregulated and 54 downregulated), and none of male-specific DEGs were obtained finally. Second, bioinformatics analysis of female-specific DEGs was performed. Gene Ontology (GO) functional annotation analysis shows that DEGs were mainly enriched in translational initiation, cytosolic ribosome, and structural constituent of ribosome. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis shows that the top 6 enrichment pathways are ribosome, nuclear factor-kappa B (NF-kappa B) signaling pathway, apoptosis, mineral absorption, nonalcoholic fatty liver disease, and pertussis. Three functional modules were clustered in the protein–protein interaction (PPI) network of DEGs. The top 10 key genes of the PPI network constructed were selected, including RPS14, RPS15A, RPS24, FAU, RPL27, RPL31, RPL34, RPL35A, RSL24D1, and EEF1B2. Sex difference of ribosome in stroke-induced peripheral immunosuppression may be the potential mechanism of sex disparities in outcome after IS, and women are more likely to have stroke-induced immunosuppression. RPS14, RPS15A, RPS24, FAU, RPL27, RPL31, RPL34, RPL35A, RSL24D1, and EEF1B2 may be novel prognostic biomarkers and potential therapeutic targets for IS.
Highlights
Stroke was the second largest cause of death worldwide after ischemic heart disease and the second most common cause of worldwide disability-adjusted life years (DALYs)
A large number of experiments in vivo have proved that estrogen has a protective effect on the brain [4, 5], there is sufficient clinic evidence that women more often had poor functional outcome compared with men, and this difference
The GSE37587 dataset contained 68 peripheral whole blood samples, which were collected from 20 women and 14 men within 24 hours from known onset of ischemic stroke (IS) symptom and again at 24-48 hours after onset. 30 nonsex-specific differentially expressed genes (DEGs) (1 upregulated and 29 downregulated) were obtained by comparison of 34 follow-up and 34 baseline samples. 79 female-specific DEGs (25 upregulated and 54 downregulated) were obtained by comparison of 20 female follow-up and 20 female baseline samples
Summary
Stroke was the second largest cause of death worldwide after ischemic heart disease and the second most common cause of worldwide disability-adjusted life years (DALYs). There were 80.1 million prevalent cases of stroke, which 84.4% contributed ischemic stroke (IS) and 13.7 million new stroke cases globally in 2016 [1]. The mean global lifetime risk of stroke increased from 22.8% in 1990 to 24.9% in 2016 [2]. Stroke occurs every 40 seconds, and stroke caused death every 3 minutes and 42 seconds in the United States [3]. Stroke is characterized by significant sex differences. The difference of sex on various aspects of stroke, such as risk factors, epidemiology, incidence, pathogenesis, mortality, prognosis, clinical presentation, and response to treatment, has been extensively investigated in the past years. A large number of experiments in vivo have proved that estrogen has a protective effect on the brain [4, 5], there is sufficient clinic evidence that women more often had poor functional outcome compared with men, and this difference
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