【作者】 王静；

【导师】 李菊香；

【作者基本信息】 南昌大学 ， 内科学（心血管病）（专业学位）， 2022， 硕士

【摘要】 目的:心房颤动有着较高的发病率、复发率、致残率以及死亡率,大多数患者伴有许多严重的并发症。随着生物信息学在医学领域中的渗透,我们发现缺乏对房颤发病机制的深入认识是治疗效果差强人意的主要原因。本文基于生物信息学筛选房颤相关的mRNA表达谱及信号通路,期望为有关房颤的临床研究提供理论依据。方法:我们收集了来自本院心脏外科所提供的样本,房颤和窦性心律样本各5例。对10例样本进行高通量mRNA测序,同时从GEO数据库获取GSE41177数据集房颤患者和窦律患者的mRNA数据,将两组数据联合分析。用R软件进行批量归一化、差异基因的筛选、GSEA富集分析及GO和KEGG富集分析可视化等。差异表达基因的蛋白互作网络由STRING数据库构建,通过Cytoscape软件筛选Hub基因。最后采用RT-q PCR以验证Hub基因在房颤组和窦律组mRNA的表达水平。结果:从两组数据集中筛选出57个共同差异表达基因,其中有56个为高表达,1个为低表达。对这些差异表达基因进行GO和KEGG富集分析,确定了其所涉及的显著富集通路,主要包括细胞外基质组织、白细胞聚集、炎症反应正调控、I型干扰素的细胞反应、细胞外结构组织、局灶黏附、细胞外基质受体相互作用、I型干扰素信号通路等。随后使用Cytoscape软件确定了前5个hub基因分别是:SERPINE1、TGFBI、BGN、ASPN、TYMP。通过GSEA富集分析验证,细胞外基质组织通路富集最明显,且参与该通路的Hub基因有BGN、ASPN、SERPINE1。对差异表达基因进行RT-q PCR,结果显示BGN、ASPN及SERPINE1的表达水平均升高,与我们上述的生物信息学分析基本相符。结论:基于生物信息学的分析,我们发现与房颤相关的BGN、ASPN及SERPINE1基因均富集在细胞外基质组织通路,可能成为房颤潜在的诊断和治疗靶点,为进一步探讨房颤的发病机制提供了有价值的信息。更多还原

【Abstract】 Objective:Atrial fibrillation has a high morbidity,recurrence,disability,and mortality rate,and most patients are associated with many serious complications.With the penetration of bioinformatics in the medical field,we found that the lack of in-depth understanding of the pathogenesis of AF is the main reason for the poor treatment outcome.In this paper,we screen the mRNA expression profiles and signalling pathways associated with atrial fibrillation based on bioinformatics,in the hope of providing a theoretical basis for clinical studies on atrial fibrillation.Methods:We collected samples from the samples provided by the cardiac surgery department of our hospital,5 samples each from atrial fibrillation and sinus rhythm.High-throughput mRNA sequencing was performed on the 10 samples,while mRNA data from patients with atrial fibrillation and sinus rhythm in the GSE41177 dataset were obtained from the GEO database,and the two sets of data were analysed jointly.Batch normalization,screening of differential genes,GSEA enrichment analysis and visualization of GO and KEGG enrichment analysis were performed using R software.Protein interaction networks for differentially expressed genes were constructed from the STRING database and Hub genes were screened by Cytoscape software.Finally,RT-q PCR was used to verify the expression levels of Hub genes in the mRNAs of the atrial fibrillation and sinus rhythm groups.Results:Fifty-seven commonly differentially expressed genes were screened from the two datasets,of which 56 were highly expressed and one was lowly expressed.GO and KEGG enrichment analysis of these differentially expressed genes identified the significant enrichment pathways involved,mainly including extracellular matrix organization,leukocyte aggregation,positive regulation of inflammatory response,cellular response to type I interferon,extracellular structural organization,focal adhesion,extracellular matrix receptor interaction,and type I interferon signaling pathway.The top 5 hub genes were subsequently identified using Cytoscape software as: SERPINE1,TGFBI,BGN,ASPN,TYMP.The extracellular matrix tissue pathway was most significantly enriched by GSEA enrichment analysis,and the hub genes involved in this pathway were BGN,ASPN,SERPINE1.The results of RT-q PCR on differentially expressed genes showed that the expression levels of BGN,ASPN and SERPINE1 were elevated,which was basically consistent with our bioinformatics analysis above.Conclusion:Based on bioinformatics analysis,we found that BGN,ASPN and SERPINE1 genes associated with AF are enriched in the extracellular matrix tissue pathway,which may become potential diagnostic and therapeutic targets for AF,providing valuable information to further explore the pathogenesis of AF.更多还原