Department of Anesthesiology, Lanzhou University Second Hospital, Lanzhou, Gansu 730030, China.
Laboratory Medicine Center, Lanzhou University Second Hospital, Lanzhou, Gansu 730030, China.
Biomed Res Int. 2020 Dec 3;2020:3650935. doi: 10.1155/2020/3650935. eCollection 2020.
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 , , , , , , , , , and . 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.
缺血性脑卒中(IS)严重威胁人类健康,导致高死亡率和大量功能丧失。最近的研究表明,IS 的结果存在性别特异性,但具体机制尚不清楚。本研究旨在确定 IS 进展中外周免疫反应的性别差异,预测可能导致性别特异性结果的潜在预后生物标志物,并揭示潜在的治疗靶点。从基因表达数据库 GEO 中下载了基因表达数据集 GSE37587,其中包括 68 例发病 24 小时内采集的外周全血样本,以及发病后 24-48 小时再次采集的样本(20 名女性和 14 名男性)。首先,通过 Bioconductor R 包,使用随访(24-48 小时)与基线(24 小时)比较,筛选出两种差异表达基因(DEGs)(非性别特异性-和性别特异性-DEGs)。最终获得了 30 个非性别特异性 DEG(1 个上调和 29 个下调)、79 个女性特异性 DEG(25 个上调和 54 个下调)和 0 个男性特异性 DEG。其次,对女性特异性 DEG 进行了生物信息学分析。GO 功能注释分析表明,DEGs 主要富集在翻译起始、胞质核糖体和核糖体结构成分中。KEGG 通路富集分析表明,前 6 个富集通路为核糖体、核因子--kappa B(NF-kappa B)信号通路、细胞凋亡、矿物质吸收、非酒精性脂肪性肝病和百日咳。DEGs 的蛋白质-蛋白质相互作用(PPI)网络中聚类了 3 个功能模块。选择 PPI 网络构建的前 10 个关键基因,包括、、、、、、、、和。脑卒中诱导的外周免疫抑制中的核糖体性别差异可能是脑卒中后结局性别差异的潜在机制,女性更易发生脑卒中诱导的免疫抑制。RPS14、RPS15A、RPS24、FAU、RPL27、RPL31、RPL34、RPL35A、RSL24D1 和 EEF1B2 可能是 IS 的新型预后生物标志物和潜在治疗靶点。