Bioinformatic gene analysis for potential biomarkers and therapeutic targets of atrial fibrillation-related stroke
Bioinformatic gene analysis for potential biomarkers and therapeutic targets of atrial fibrillation-related stroke
复制标题
房颤相关卒中潜在生物标志物和治疗靶点的生物信息基因分析
DOI：
10.1186/s12967-019-1790-x
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发表时间：
2019-02-13
影响因子：
7.4
通讯作者：
Hua, Ping
中科院分区：
文献类型：
--
作者：
Zou, Rongjun;Zhang, Dingwen;Hua, Ping
背景：房颤是最常见的持续性心律失常之一，然而，流行病学数据可能低估了其实际患病率。同时，由于心律不齐、慢性血管炎症、肾功能不全和血瘀证的并存，房颤被认为是缺血性中风的主要原因。为了了解心房颤动(房颤)与卒中之间的关系，揭示房颤相关卒中的潜在生物标志物和治疗靶点，我们对共表达基因进行了研究。方法：通过生物信息学分析基因表达总表(GEO)数据库GSE79768和GSE58294分别筛选出与房颤和卒中相关的差异表达基因(DEG)。随后，使用广泛的靶点预测和网络分析方法评估蛋白质-蛋白质相互作用(PPI)网络、基因本体论(GO)术语和DEGS的途径丰富，并评估与房颤和卒中相关的共表达的DEG和相应的预测miRNAs。结果：我们在3、5和24 h的左房标本和心源性卒中血液样本中分别检测到489、265、518和592个DEG。LRRK2、CALM1、CXCR4、TLR4、CTNNB1和CXCR2可能与房颤有关，CD19、FGF9、SOX9、GNGT1和NOG等杂合基因可能与卒中有关。ZNF566、PDZK1IP1、ZFHX3和PITX2共表达的deg与相应的miRNAs结合，特别是miR-27a-3p、miR-27b-3p和miR-494-3p可能与房颤相关卒中显著相关。结论：房颤与卒中相关，ZNF566、PDZK1IP1、ZFHX3和PITX2基因与参与房颤相关卒中的新生物标志物显著相关。
Background: Atrial fibrillation (AF) is one of the most prevalent sustained arrhythmias, however, epidemiological data may understate its actual prevalence. Meanwhile, AF is considered to be a major cause of ischemic strokes due to irregular heart-rhythm, coexisting chronic vascular inflammation, and renal insufficiency, and blood stasis. We studied co-expressed genes to understand relationships between atrial fibrillation (AF) and stroke and reveal potential biomarkers and therapeutic targets of AF-related stroke.Methods: AF-and stroke-related differentially expressed genes (DEGs) were identified via bioinformatic analysis Gene Expression Omnibus (GEO) datasets GSE79768 and GSE58294, respectively. Subsequently, extensive target prediction and network analyses methods were used to assess protein-protein interaction (PPI) networks, Gene Ontology (GO) terms and pathway enrichment for DEGs, and co-expressed DEGs coupled with corresponding predicted miRNAs involved in AF and stroke were assessed as well.Results: We identified 489, 265, 518, and 592 DEGs in left atrial specimens and cardioembolic stroke blood samples at < 3, 5, and 24 h, respectively. LRRK2, CALM1, CXCR4, TLR4, CTNNB1, and CXCR2 may be implicated in AF and the hubgenes of CD19, FGF9, SOX9, GNGT1, and NOG may be associated with stroke. Finally, co-expressed DEGs of ZNF566, PDZK1IP1, ZFHX3, and PITX2 coupled with corresponding predicted miRNAs, especially miR-27a-3p, miR-27b-3p, and miR-494-3p may be significantly associated with AF-related stroke.Conclusion: AF and stroke are related and ZNF566, PDZK1IP1, ZFHX3, and PITX2 genes are significantly associated with novel biomarkers involved in AF-related stroke.