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生物信息学分析以识别ST段抬高型心肌梗死相关缺血性卒中的潜在生物标志物和治疗靶点。

Bioinformatics analysis to identify potential biomarkers and therapeutic targets for ST-segment-elevation myocardial infarction-related ischemic stroke.

作者信息

Feng Shuo, Li Rui, Zhou Qingqing, Qu Fengling, Hu Wei, Liu Xinfeng

机构信息

Stroke Center and Department of Neurology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

出版信息

Front Neurol. 2022 Aug 11;13:894289. doi: 10.3389/fneur.2022.894289. eCollection 2022.

DOI:10.3389/fneur.2022.894289
PMID:36034287
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9403764/
Abstract

BACKGROUND

Acute myocardial infarction (AMI) is one of the major causes of mortality and disability worldwide, and ischemic stroke (IS) is a serious complication after AMI. In particular, patients with ST-segment-elevation myocardial infarction (STEMI) are more susceptible to IS. However, the interrelationship between the two disease mechanisms is not clear. Using bioinformatics tools, we investigated genes commonly expressed in patients with STEMI and IS to explore the relationship between these diseases, with the aim of uncovering the underlying biomarkers and therapeutic targets for STEMI-associated IS.

METHODS

Differentially expressed genes (DEGs) related to STEMI and IS were identified through bioinformatics analysis of the Gene Expression Omnibus (GEO) datasets GSE60993 and GSE16561, respectively. Thereafter, we assessed protein-protein interaction networks, gene ontology term annotations, and pathway enrichment for DEGs using various prediction and network analysis methods. The predicted miRNAs targeting the co-expressed STEMI- and IS-related DEGs were also evaluated.

RESULTS

We identified 210 and 29 DEGs in GSE60993 and GSE16561, respectively. CD8A, TLR2, TLR4, S100A12, and TREM1 were associated with STEMI, while the hubgenes, IL7R, CCR7, FCGR3B, CD79A, and ITK were implicated in IS. In addition, binding of the transcripts of the co-expressed DEGs MMP9, ARG1, CA4, CRISPLD2, S100A12, and GZMK to their corresponding predicted miRNAs, especially miR-654-5p, may be associated with STEMI-related IS.

CONCLUSIONS

STEMI and IS are related and MMP9, ARG1, CA4, CRISPLD2, S100A12, and GZMK genes may be underlying biomarkers involved in STEMI-related IS.

摘要

背景

急性心肌梗死(AMI)是全球范围内导致死亡和残疾的主要原因之一,缺血性中风(IS)是AMI后的一种严重并发症。特别是,ST段抬高型心肌梗死(STEMI)患者更容易发生IS。然而,这两种疾病机制之间的相互关系尚不清楚。我们使用生物信息学工具研究了STEMI和IS患者中共同表达的基因,以探索这些疾病之间的关系,旨在揭示STEMI相关IS的潜在生物标志物和治疗靶点。

方法

分别通过对基因表达综合数据库(GEO)数据集GSE60993和GSE16561进行生物信息学分析,鉴定与STEMI和IS相关的差异表达基因(DEG)。此后,我们使用各种预测和网络分析方法评估DEG的蛋白质-蛋白质相互作用网络、基因本体术语注释和通路富集情况。还评估了靶向共表达的STEMI和IS相关DEG的预测miRNA。

结果

我们在GSE60993和GSE16561中分别鉴定出210个和29个DEG。CD8A、TLR2、TLR4、S100A12和TREM1与STEMI相关,而中心基因IL7R、CCR7、FCGR3B、CD79A和ITK与IS有关。此外,共表达的DEG MMP9、ARG1、CA4、CRISPLD2、S100A12和GZMK的转录本与其相应的预测miRNA,尤其是miR-654-5p的结合,可能与STEMI相关的IS有关。

结论

STEMI和IS相关,MMP9、ARG1、CA4、CRISPLD2、S100A和GZMK基因可能是参与STEMI相关IS的潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9419/9403764/b0cfeb52d54f/fneur-13-894289-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9419/9403764/ca1555892f8e/fneur-13-894289-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9419/9403764/5ac80382dd4b/fneur-13-894289-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9419/9403764/8bc5ba45043b/fneur-13-894289-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9419/9403764/d8e3c52f4b09/fneur-13-894289-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9419/9403764/360ee36f4af8/fneur-13-894289-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9419/9403764/b0cfeb52d54f/fneur-13-894289-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9419/9403764/ca1555892f8e/fneur-13-894289-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9419/9403764/5ac80382dd4b/fneur-13-894289-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9419/9403764/8bc5ba45043b/fneur-13-894289-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9419/9403764/d8e3c52f4b09/fneur-13-894289-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9419/9403764/360ee36f4af8/fneur-13-894289-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9419/9403764/b0cfeb52d54f/fneur-13-894289-g0006.jpg

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