Integrated analysis of ischemic stroke datasets revealed sex and age difference in anti-stroke targets.
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ABSTRACT:
SUBMITTER: Li WX
PROVIDER: S-EPMC5028792 | biostudies-literature | 2016
REPOSITORIES: biostudies-literature
Publications
Integrated analysis of ischemic stroke datasets revealed sex and age difference in anti-stroke targets.
Li Wen-Xing WX Dai Shao-Xing SX Wang Qian Q Guo Yi-Cheng YC Hong Yi Y Zheng Jun-Juan JJ Liu Jia-Qian JQ Liu Dahai D Li Gong-Hua GH Huang Jing-Fei JF
PeerJ 20160915
Ischemic stroke is a common neurological disorder and the burden in the world is growing. This study aims to explore the effect of sex and age difference on ischemic stroke using integrated microarray datasets. The results showed a dramatic difference in whole gene expression profiles and influenced pathways between males and females, and also in the old and young individuals. Furthermore, compared with old males, old female patients showed more serious biological function damage. However, femal ...[more]
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Project description: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.
| S-EPMC7735851 | biostudies-literature
Project description:BackgroundStroke incidence is decreasing in most developing countries. However, worrisome trends of an increase in the younger population have been described.AimTo investigate sex differences and longitudinal changes in ischemic stroke regarding incidence, cardiovascular risk factors, and outcome, in the young.MethodsThis is an observational study based on the data from the Swedish national stroke registry, Riksstroke. Patients, 18-54 years of age, having ischemic stroke between 2005 and 2018 were included, resulting in a study population of 16,210 patients.ResultsThe incidence was higher in men than in women (30.6 vs. 19.1 per 100,000, P < 0.001). After an initial increase, the incidence stabilized and then decreased, resulting in a similar level in 2018 as in 2005. Atrial fibrillation, diabetes, and usage of anti-hypertensives at stroke onset were more common among men and did not change over time. Smoking was common and slightly more so in women, but with a reduced prevalence in both men and women during the study period. Dependency in Activities of Daily Living (ADL) and case fatality showed no clear trends or sex differences.ConclusionsThe results show that there are sex differences in ischemic stroke in the younger age group regarding incidence and vascular risk factors, particularly smoking. Temporal trends in stroke incidence are difficult to interpret as fluctuations are substantial, largely due to stroke being quite uncommon in the younger population.
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Project description:Background and purposeEstimating age- and sex-specific population attributable risks (PARs) of major risk factors for stroke may be a useful strategy to identify risk factors for targeting preventive strategies.MethodsFor this case-control matched study, consecutive patients aged 18-90 years and admitted to nine nationwide hospitals with acute ischemic stroke between December 2008 and June 2010, were enrolled as cases. Controls, individually matched by age and sex, were chosen from the 4th Korean National Health & Nutrition Examination Survey (2008-2010). Based on odds ratios and prevalence, standardized according to the age and sex structure of the Korean population, PARs of major risk factors were estimated according to age (young, ≤ 45; middle-aged, 46-65; and elderly, ≥ 66 years) and sex subgroups.ResultsIn 4,743 matched case-control sets, smoking (PAR, 45.1%) was the greatest contributing risk factor in young men, followed by hypertension (28.5%). In middle-aged men, the greatest contributing factors were smoking (37.4%), hypertension (22.7%), and diabetes (14.6%), whereas in women the greatest factors were hypertension (22.7%) and stroke history (10.6%). In the elderly, hypertension was the leading factor in men (23.7%) and women (23.4%). Other noticeable factors were stroke history (men, 19.7%; women, 17.3%) and diabetes (men, 12.5%; women, 15.1%). In young women, risk factors with a PAR greater than 10% were not found.ConclusionsSmoking cessation in young people and hypertension and diabetes control in older people may be effective in reducing the burden of stroke on the population. In the elderly, secondary prevention could also be emphasized.
| S-EPMC4635707 | biostudies-literature
Project description:Breast cancer is one of the primary threats to women's health worldwide. However, the molecular mechanisms underlying the development of breast cancer remain to be fully elucidated. The present study aimed to investigate specific target gene expression profiles in breast cancer tissues in general and in different breast cancer stages, as well as to explore their functions in tumor development. For integrated analysis, a total of 5 gene expression profiling datasets for 3 different stages of breast cancer (stages I-III) were downloaded from the Gene Expression Omnibus of the National Center for Biotechnology Information. Pre-processing of these datasets was performed using the Robust Multi-array Average algorithm and global renormalization was performed for all studies. Differentially expressed genes between breast cancer patients and controls were estimated using the empirical Bayes algorithm. The Database for Annotation, Visualization and Integrated Discovery web server was used for analyzing the enrichment of the differentially expressed genes in Gene Ontology terms of the category biological process and in Kyoto Encyclopedia of Genes and Genomes pathways. Furthermore, breast cancer target genes were downloaded from the Thomson Reuters Integrity Database. We merged these target genes with the genes in breast cancer datasets. Analysis of anti-breast cancer gene networks was performed using the Genome-scale Integrated Analysis of Gene Networks in Tissues web server. The results demonstrated that the normal functions of the cell cycle, cell migration and cell adhesion were altered in all stages of breast cancer. Furthermore, 12 anti-breast cancer genes were identified to be dysregulated in at least one of the three stages. Among all of these genes, ribonucleotide reductase regulatory subunit M2 (RRM2) exhibited the highest degree of interaction with other interacting genes. Analysis of the network interactions revealed that the transcription factor of RRM2 is crucial for cancer development. Other genes, including mucin 1, progesterone receptor and cyclin-dependent kinase 5 regulatory subunit associated protein 3, also exhibited a high degree of interaction with the associated genes. In conclusion, several key anti-breast cancer genes identified in the present study are mainly associated with the regulation of the cell cycle, cell migration, cell adhesion and other cancer-associated cell functions, particularly RRM2.
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Project description:Background Although large artery stiffness has been implicated in the pathogenesis of cerebral small vessel disease, whether carotid pulsatility, a convenient surrogate marker of arterial stiffness, is similarly associated with global burden of small vessel disease is unknown. Aims To determine the age and sex-specific associations of carotid pulsatility with global burden of small vessel disease. Methods We studied consecutive patients with transient ischemic attack or non-disabling ischemic stroke from the Oxford Vascular Study who had a brain MRI and carotid duplex ultrasound during 2002-2014. We determined clinical correlates of common carotid artery (CCA) and internal carotid artery (ICA) pulsatility index (PI) and their associations with the total small vessel disease score on MRI, stratified by age (median = 72). Results In 587 patients, correlates of CCA and ICA-PI were both independently associated with age, diabetes, and premorbid mean pulse pressure after adjustment for age, sex, and cardiovascular risk factors (all p < 0.05). ICA-PI was strongly associated with small vessel disease markers and burden, particularly lacunes, in patients aged<70 (age and sex-adjusted odds ratio of top vs. bottom pulsatility index quartile: 5.35, 1.95-14.70, p = 0.001; increasing small vessel disease score: 2.30, 1.01-5.25, p = 0.048), but not in patients aged ≥ 70 ( p > 0.05). No associations between CCA-PI with small vessel disease score were noted at any age. In 94 consecutive patients who also received transcranial Doppler ultrasound, strong associations between middle cerebral artery (MCA)-PI and an increasing small vessel disease score were noted (unadjusted OR-MCA: 4.26, 1.45-12.55, p = 0.009; ICA: 2.37, 0.81-6.87, p = 0.11; CCA: 1.33, 0.45-3.96, p=0.61). Conclusions ICA and MCA-PI are associated with global small vessel disease burden, especially in individuals aged<70 and may be causally related.
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Project description:Although a relationship between depression and cardiovascular events has been suggested, past study results regarding the risk of stroke in relation to depression by subgroups are ambiguous. The aim of this study was to investigate the influence of depressive symptoms on risk of incident ischemic stroke in elderly according to age and sex. This prospective cohort study followed up 3852 subjects older than 55 years. Baseline depressive symptoms were defined by a score ? 5 on the Geriatric Depression Scale or antidepressant intake. The outcome measure was incident ischemic stroke within 6 years of follow-up. Multivariate Cox-proportional hazard models as well as cumulative survival analyses were computed. A total of 156 ischemic strokes occurred during the study period (24 strokes in the age-group<65 years and 132 strokes in the age-group ? 65 years). The distribution of strokes in sex-subgroups was 4.5% in men and 3.7% in women. The multivariate analysis showed an elevated stroke risk (Hazard Ratio (HR): 2.84, 95% CI 1.11-7.29, p?=?0.030) in subjects from 55 to 64 years with depressive symptoms at baseline but not in subjects older than 65 years. In the multivariate analysis according to sex the risk was increased in women (HR: 1.62, 95% CI 1.02-2.57, P?=?0.043) but not in men. The Cox-regression model for interaction showed a significant interaction between age and sex (HR: 3.24, 95% CI 1.21-8.69, P?=?0.020). This study corroborates that depressive symptoms pose an important risk for ischemic stroke, which is particularly remarkable in women and patients younger than 65 years.
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Project description: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.
| S-EPMC6941802 | biostudies-literature
Project description:AimsA post hoc analysis of RICAMIS trial to evaluate functional outcomes in relation to patient age.MethodsPatients in RICAMIS were divided into six age groups. The primary outcome was excellent functional outcome at 90 days, defined as modified Rankin Scale (mRS) score of 0-1. Compared with patients receiving usual care alone, we investigated the association of remote ischemic conditioning (RIC) effect with functional outcomes in each group and the interaction between RIC effect and age.ResultsOf 1776 patients, 498 were assigned to <60 years, 326 to 60 to <65 years, 325 to 65 to <70 years, 278 to 70 to <75 years, 206 to 75 to <80 years, and 143 to ≥80 years. Higher proportions of primary outcome were found associated with RIC in <60 years group (72.6% vs. 64.8%; adjusted risk difference [RD], 6.8%; 95% CI, -1.6% to 15.1%; p = 0.11), 60 to <65 years group (70.7% vs. 67.1%; adjusted RD, 3.1%; 95% CI, -7.2% to 13.3%; p = 0.56), 65 to <70 years group (70.5% vs. 63.6%; adjusted RD, 3.5%; 95% CI, -6.8% to 13.8%; p = 0.51), 70 to <75 years group (59.7% vs. 54.9%; adjusted RD, 4.7%; 95% CI, -7.1% to 16.4%; p = 0.61), 75 to <80 years group (61.5% vs. 55.9%; adjusted RD, 5.7%; 95% CI, -7.8% to 19.1%; p = 0.41), and ≥ 80 years group (59.2% vs. 59.7%; adjusted RD, -2.6%; 95% CI, -18.8% to 13.5%; p = 0.75). No significant interaction between RIC effect and age was found among groups.ConclusionsThis is the first report that RIC effect may be attenuated with increasing age in patients with acute moderate ischemic stroke with respect to functional outcome.
| S-EPMC10916442 | biostudies-literature
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.
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