Investigating potential ferroptosis-related differentially expressed genes and biomarkers of ischemic stroke in elderly women using bioinformatics

Investigating potential ferroptosis-related differentially expressed genes and biomarkers of ischemic stroke in elderly women using bioinformatics
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利用生物信息学研究老年女性缺血性中风的潜在铁死亡相关差异表达基因和生物标志物

DOI:
10.26355/eurrev_202207_29199
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发表时间:
2022-01-01
影响因子:
3.3
通讯作者:
Qin, L-H
Qin, L-H
中科院分区:
医学4区
文献类型:
--
作者:
Li, S.;Li, Z-Y;Qin, L-H

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目的:女性一生中患中风的风险比男性更高,也更有可能死于中风。铁细胞凋亡是最近发现的一种程序性细胞死亡形式,与许多疾病有关。铁中毒相关基因在诊断、预后中的作用。老年女性缺血性卒中(IS)的治疗需要进一步的澄清。本研究旨在筛选与老年女性IS相关的铁蛋白沉积症相关基因,寻找中枢基因和候选药物。材料与方法:通过生物信息学分析GSE 22255和铁蛋白沉积症相关基因数据集,筛选老年女性IS患者铁蛋白沉积症相关差异表达基因(DEG)。随后,我们利用铁固酸相关的枢纽基因预测靶向的miRNA,构建miRNA-mRNA网络,并鉴定候选药物。基因本体论和京都基因和基因组百科全书分析显示,这11个基因主要富集在IL-17中。TNF和NF-κ B信号通路。而且。hub基因提示了10个与IS相关的生物标志物,包括SOCS 1、IFNG、TNFAIP 3、IL 1B、IL-6、PTGS 2、DDIT 3、CXCL 2、NFE 2L 2。ATF3此外,我们的研究结果揭示了枢纽基因的miRNA-mRNA网络,并确定了候选药物。10个潜在的治疗化合物,特别是雌二醇CTD 00005920,对应于10个关键基因,可能是老年妇女IS治疗的靶点。结论:我们的研究结果表明,铁中毒相关DEG(SOCS 1,1FNG,TNFAIP 3,IL 1B,IL-6,PTGS 2,DDIT 3,CXCL 2,NFE 2L 2.和ATF 3)作为IS诊断、预后和治疗的潜在生物标志物,为铁凋亡在老年女性IS中的重要作用提供了额外的证据。
OBJECTIVE: Women have a higher lifetime risk of stroke than men and are more likely to die from it. Ferroptosis is a recently discovered form of programmed cell death implicated in many diseases. The role of ferroptosis-related genes in the diagnosis, prognosis. and treatment of elderly women with ischemic stroke (IS) requires additional clarification. This paper aimed to screen ferroptosis-related genes associated with IS in elderly women and to identify hub genes and candidate drugs.MATERIALS AND METHODS: Ferroptosis-related differentially expressed genes (DEGs) in elderly women with IS were identified by bioinformatics analysis of the GSE22255 and ferroptosis-related gene datasets. Subsequently, ferroptosis-related hub genes were used to predict targeted miRNA, construct the miRNA-mRNA network, and identify candidate drugs.RESULTS: Eleven ferroptosis-related DEGs were identified in elderly women with IS vs. controls. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis revealed that the 11 genes were mainly enriched in the IL-17. TNF, and NF-kappa B signaling pathways. Moreover. the hub genes suggested 10 ferroptosis-related biomarkers for IS, including SOCS1, IFNG, TNFAIP3, IL1B, IL-6, PTGS2, DDIT3, CXCL2, NFE2L2. and ATF3. Furthermore, our findings revealed the miRNA-mRNA network of the hub genes and identified candidate drugs. 10 potential therapeutic compounds, especially estradiol CTD 00005920, corresponded to the 10 key genes which could be targets for IS treatment in elderly women.CONCLUSIONS: Our results suggested ferroptosis-related DEGs (SOCS1, 1FNG, TNFAIP3, IL1B, IL-6, PTGS2, DDIT3, CXCL2, NFE2L2. and ATF3) as potential biomarkers for IS diagnosis, prognosis, and treatment, providing additional evidence of the important role of ferroptosis in IS in elderly women.