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使用生物信息学方法探究老年女性缺血性脑卒中潜在的铁死亡相关差异表达基因和生物标志物。

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

机构信息

School of Informatics, School of Nursing, Key Laboratory of Hunan Province for Prevention and Treatment of Integrated Traditional Chinese and Western Medicine on Cardiocerebral Diseases, Hunan University of Chinese Medicine, Changsha, China.

出版信息

Eur Rev Med Pharmacol Sci. 2022 Jul;26(13):4744-4754. doi: 10.26355/eurrev_202207_29199.

Abstract

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-κB 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, IFNG, 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.

摘要

目的

女性一生中患中风的风险高于男性,且更有可能死于中风。铁死亡是一种新发现的程序性细胞死亡形式,与许多疾病有关。铁死亡相关基因在老年女性缺血性中风(IS)的诊断、预后和治疗中的作用尚需进一步阐明。本研究旨在筛选与老年女性 IS 相关的铁死亡相关基因,并鉴定关键基因和候选药物。

材料和方法

通过生物信息学分析 GSE22255 和铁死亡相关基因数据集,筛选老年女性 IS 中与铁死亡相关的差异表达基因(DEGs)。随后,利用铁死亡相关的关键基因预测靶向 miRNA,构建 miRNA-mRNA 网络,并鉴定候选药物。

结果

在老年女性 IS 与对照组中,共鉴定出 11 个铁死亡相关 DEGs。GO 和 Kyoto Encyclopedia of Genes and Genomes 分析显示,这 11 个基因主要富集在 IL-17、TNF 和 NF-κB 信号通路中。此外,关键基因提示 10 个与 IS 相关的铁死亡相关生物标志物,包括 SOCS1、IFNG、TNFAIP3、IL1B、IL-6、PTGS2、DDIT3、CXCL2、NFE2L2 和 ATF3。此外,本研究还揭示了关键基因的 miRNA-mRNA 网络,并鉴定了候选药物。10 种潜在的治疗化合物,特别是雌二醇 CTD 00005920,与 10 个关键基因相对应,这些基因可能成为老年女性 IS 治疗的靶点。

结论

本研究结果提示铁死亡相关 DEGs(SOCS1、IFNG、TNFAIP3、IL1B、IL-6、PTGS2、DDIT3、CXCL2、NFE2L2 和 ATF3)可作为 IS 诊断、预后和治疗的潜在生物标志物,为铁死亡在老年女性 IS 中的重要作用提供了更多证据。

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