整合鉴定心房颤动相关脑卒中发病相关的枢纽基因。

Integrative identification of hub genes in development of atrial fibrillation related stroke.

机构信息

Department of Cardiothoracic Surgery, Huashan Hospital of Fudan University, Shanghai, China.

Department of Physiology, Hebei Medical University, Shijiazhuang, China.

出版信息

PLoS One. 2023 Mar 23;18(3):e0283617. doi: 10.1371/journal.pone.0283617. eCollection 2023.

DOI:10.1371/journal.pone.0283617

PMID:36952494

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10035830/

Abstract

BACKGROUND

As the most common arrhythmia, atrial fibrillation (AF) is associated with a significantly increased risk of stroke, which causes high disability and mortality. To date, the underlying mechanism of stroke occurring after AF remains unclear. Herein, we studied hub genes and regulatory pathways involved in AF and secondary stroke and aimed to reveal biomarkers and therapeutic targets of AF-related stroke.

METHODS

The GSE79768 and GSE58294 datasets were used to analyze AF- and stroke-related differentially expressed genes (DEGs) to obtain a DEG1 dataset. Weighted correlation network analysis (WGCNA) was used to identify modules associated with AF-related stroke in GSE66724 (DEG2). DEG1 and DEG2 were merged, and hub genes were identified based on protein-protein interaction networks. Gene Ontology terms were used to analyze the enriched pathways. The GSE129409 and GSE70887 were applied to construct a circRNA-miRNA-mRNA network in AF-related stroke. Hub genes were verified in patients using quantitative real-time polymerase chain reaction (qRT-PCR).

RESULTS

We identified 3,132 DEGs in blood samples and 253 DEGs in left atrial specimens. Co-expressed hub genes of EIF4E3, ZNF595, ZNF700, MATR3, ACKR4, ANXA3, SEPSECS-AS1, and RNF166 were significantly associated with AF-related stroke. The hsa_circ_0018657/hsa-miR-198/EIF4E3 pathway was explored as the regulating axis in AF-related stroke. The qRT-PCR results were consistent with the bioinformatic analysis.

CONCLUSIONS

Hub genes EIF4E3, ZNF595, ZNF700, MATR3, ACKR4, ANXA3, SEPSECS-AS1, and RNF166 have potential as novel biomarkers and therapeutic targets in AF-related stroke. The hsa_circ_0018657/hsa-miR-198/EIF4E3 axis could play an important role regulating the development of AF-related stroke.

摘要

背景

作为最常见的心律失常，心房颤动（AF）与中风风险显著增加相关，这导致高残疾和死亡率。迄今为止，AF 后发生中风的潜在机制仍不清楚。在此，我们研究了与 AF 和继发性中风相关的枢纽基因和调控途径，旨在揭示 AF 相关中风的生物标志物和治疗靶点。

方法

使用 GSE79768 和 GSE58294 数据集分析 AF 和中风相关差异表达基因（DEGs）以获得 DEG1 数据集。使用加权相关网络分析（WGCNA）在 GSE66724 中识别与 AF 相关中风相关的模块（DEG2）。合并 DEG1 和 DEG2，并基于蛋白质-蛋白质相互作用网络识别枢纽基因。使用基因本体论术语分析富集途径。应用 GSE129409 和 GSE70887 在 AF 相关中风中构建 circRNA-miRNA-mRNA 网络。使用定量实时聚合酶链反应（qRT-PCR）在患者中验证枢纽基因。

结果

我们在血液样本中鉴定了 3132 个 DEG，在左心房标本中鉴定了 253 个 DEG。EIF4E3、ZNF595、ZNF700、MATR3、ACKR4、ANXA3、SEPSECS-AS1 和 RNF166 的共表达枢纽基因与 AF 相关中风显著相关。hsa_circ_0018657/hsa-miR-198/EIF4E3 通路被探索为 AF 相关中风的调节轴。qRT-PCR 结果与生物信息学分析一致。

结论

EIF4E3、ZNF595、ZNF700、MATR3、ACKR4、ANXA3、SEPSECS-AS1 和 RNF166 等枢纽基因可能成为 AF 相关中风的新型生物标志物和治疗靶点。hsa_circ_0018657/hsa-miR-198/EIF4E3 轴可能在调节 AF 相关中风的发展中发挥重要作用。