Dataset Information

Sex-specific and opposite modulatory aspects revealed by PPI network and pathway analysis of ischemic stroke in humans.

ABSTRACT: BACKGROUND:Ischemic 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. METHODS:Gene 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. RESULTS:In 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. CONCLUSION:The 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.

SUBMITTER: Lv Y

PROVIDER: S-EPMC6941802 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Sex-specific and opposite modulatory aspects revealed by PPI network and pathway analysis of ischemic stroke in humans.

Lv Yan Y He X Y XY Li Dongguo D Liu Tao T Wen G Q GQ Li Junfa J

PloS one 20200103 1

<h4>Background</h4>Ischemic 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.<h4>Methods</h4>Gene 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-val ...[more]

PMID: 31899762

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Project description:Background and Purpose- We determined the effect of sex on outcome after endovascular stroke thrombectomy in acute ischemic stroke, including lifelong disability outcomes. Methods- We analyzed patients treated with the Solitaire stent retriever in the combined SWIFT (Solitaire FR With the Intention for Thrombectomy), STAR (Solitaire FR Thrombectomy for Acute Revascularization), and SWIFT PRIME (Solitaire FR With the Intention for Thrombectomy as Primary Endovascular Treatment) cohorts. Ordinal and logistic regression were used to examine known factors influencing outcome after endovascular stroke thrombectomy and study the effect of sex on the association between these factors and outcomes, including age and time to reperfusion. Years of optimal life after thrombectomy were defined as disability-adjusted life years and calculated by projecting disability through adjusted poststroke life expectancy by sex. Results- Among 389 patients treated with endovascular stroke thrombectomy, 55% were females, and median National Institutes of Health Stroke Scale was 17 (interquartile range, 8-28). There were no differences between females versus males in presenting deficit severity (National Institutes of Health Stroke Scale score, 17 versus 17, P=0.21), occlusion location (69% versus 64% M1, P=0.62), presenting infarct extent (Alberta Stroke Program Early CT Score 8 versus 8, P=0.24), rate of substantial reperfusion (Thrombolysis in Cerebral Infarction 2b/3, 87% versus 83%, P=0.37), onset to reperfusion time (294 versus 302 minutes, P=0.46). Despite older ages (69 versus 64, P<0.001) and higher rate of atrial fibrillation (45% versus 30%, P=0.002) for females compared with males, adjusted rates of functional independence at 90 days were similar (odds ratio, 1.0; 95% CI, 0.6-1.6). After adjusting for age at presentation and stroke severity, females had more years of optimal life (disability-adjusted life year) after endovascular stroke thrombectomy, 10.6 versus 8.5 years (P<0.001). Conclusions- Despite greater age and higher rate of atrial fibrillation, females experienced comparable functional outcomes and greater years of optimal life after intervention compared with males.

Project description:PurposeReperfusion therapies for acute ischemic stroke due to large-vessel occlusion (AIS-LVO) are highly time-dependent, and large infarction is related to poor outcomes and risk of symptomatic hemorrhage. It is of significance to investigate and optimize the screening means and selection criteria for reperfusion therapies to identify more appropriate patients with better outcomes. This study aimed to compare the performance of attenuation changes vs. automated Alberta Stroke Program Early CT Score (ASPECTS) and using CT angiography (CTA) source images vs. non-contrast CT (NCCT) in distinguishing the infarction extent of ischemic core volumes ≥ 70 ml within different time windows.MethodsA total of 73 patients with AIS-LVO who received multimodal CT were analyzed. The automated software was used to calculate ASPECTS. Attenuation change was defined as the sum of products of relative Hounsfield unit (rHU) values times weighting factors of all 10 ASPECTS regions. rHU value of each region was the HU of the ischemic side over that of the contralateral. The corresponding weighting factors were the regression coefficients derived from a multivariable linear regression model which was used to correlate regional rHU with ischemic core volumes, because each region in the ASPECTS template is weighted disproportionally in the ASPECTS system. Automated ASPECTS and attenuation changes were both calculated using CTA and NCCT, respectively.ResultsAttenuation changes were correlated with ischemic core volumes within different time windows (Rho ranging from 0.439 to 0.637). In classification of the ischemic core ≥ 70 ml, the performances of attenuation changes were comparable with ASPECTS (area under the curve [AUC] ranging from 0.799 to 0.891), with DeLong's test (P = 0.079, P = 0.373); using CTA (AUC = 0.842) was not different from NCCT (AUC = 0.838).ConclusionAttenuation changes in ASPECTS regions were correlated with ischemic core volumes. In the classification of infarction volumes, attenuation changes had a high diagnostic ability comparable with automated ASPECTS. Measurement of attenuation changes is not involved in complicated scoring algorithms. This measurement can be used as an available, rapid, reliable, and accurate means to evaluate infarction extent within different time windows. The usefulness of infarction volumes measured by attenuation changes to identify more appropriate patients for reperfusion therapies can be validated in future clinical trials.

Dataset Information

Sex-specific and opposite modulatory aspects revealed by PPI network and pathway analysis of ischemic stroke in humans.

Publications

Sex-specific and opposite modulatory aspects revealed by PPI network and pathway analysis of ischemic stroke in humans.

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