基于生物信息学的糖尿病心肌病生物标志物及关键通路的筛选
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(1.武汉大学人民医院心血管内科,武汉大学心血管病研究所,心血管病学湖北省重点实验室,武汉 430060;2.武汉大学人民医院神经外科,武汉 430060)

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R541

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国家自然科学基金(81530012;81470516)


Screening of biomarkers and key pathways in diabetic cardiomyopathy based on bioinformatics analysis
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(1.Department of Cardiology, Cardiovascular Research Institute of Wuhan University, Hubei Key Laboratory of Cardiology, Wuhan 430060, China;2.Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan 430060, China)

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    摘要:

    目的 通过对基因表达(GEO)数据库中糖尿病心肌病(DCM)相关的基因芯片进行生物信息学分析,获得DCM的生物标志物及其调控的关键通路。方法 从GEO数据库获取DCM的基因表达芯片(GSE26887),并借助DAVID在线分析平台对这些基因进行基因本体论(GO)富集分析和京都基因与基因组百科全书(KEGG)信号通路分析,同时利用生物信息学软件STRING 10.0构建这些基因的蛋白-蛋白相互作用(PPI)网络。结果 本研究中所采用的芯片GSE26887共包含7例DCM患者及5名健康对照。共筛选出差异表达基因(DEGs)236个,包括134个上调基因及102个下调基因。其中,差异最大的5个上调基因依次为NPPA、SFRP4、DSC1、NEB及FRZB;差异最大的5个下调基因依次为SERPINE1、SERPINA3、ANKRD2、XRCC4及S100A8。GO和KEGG结果表明,DCM发展过程中的DEGs主要富集在炎症、免疫紊乱、代谢紊乱、线粒体功能障碍等方面。PPI网络揭示连接度最高的15个hub基因依次为IL-6、MYC、ACTA2、SERPINE1、ASPN、SPP1、KIT、TFRC、FMOD、PDE5A、MYH6、FPR1、C3、CDKN1A及SOCS3。结论 DCM患者的DEGs与炎症、免疫紊乱及能量代谢密切相关,本研究所筛选出的差异最大的5个上调基因和5个下调基因有望成为DCM诊断的标志分子,15个hub基因有望成为DCM治疗的靶点。

    Abstract:

    Objective To investigate the potential biomarkers and key pathways in regulation implicated with diabetic cardiomyopathy (DCM) by analyzing the gene chips in gene expression omnibus (GEO) database. Methods GSE26887 was selected from GEO database to identify the differentially expressed genes (DEGs). DAVID was applied to perform gene ontology (GO) and the Kyoto encyclopedia of genes and genomes (KEGG) analyses. A protein-protein interaction (PPI) network was also constructed to visualize the interactions among these DEGs using bioinformatics statistics STRING 10.0. Results GSE26887 contained 7 DCM patients and 5 healthy individuals. A total of 236 DEGs were captured, including 134 upregulated and 102 downregulated genes. The top-5 upregulated DEGs were NPPA, SFRP4, DSC1, NEB and FRZB, and the top-5 of down-regulation were SERPINE1, SERPINA3, ANKRD2, XRCC4 and S100A8. The results of GO and KEGG disclosed that these DEGs were significantly enriched in inflammation, immune disorders, metabolic disturbance and mitochondrial dysfunction in the development of DCM. The top 15 hub genes with the highest connectivity in the PPI network were IL-6, MYC, ACTA2, SERPINE1, ASPN, SPP1, KIT, TFRC, FMOD, PDE5A, MYH6, FPR1, C3, CDKN1A and SOCS3 in order. Conclusion Our obtained DEGs are closely associated with inflammation, immune disorders and metabolic disturbance in DCM. The top 5 upregulated and the top 5 downregulated DEGs may be regarded biomarkers for DCM diagnosis, and the 15 hub genes be the target for the treatment.

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李宁,吴海明,耿荣鑫,唐其柱.基于生物信息学的糖尿病心肌病生物标志物及关键通路的筛选[J].中华老年多器官疾病杂志,2019,18(5):321~326

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  • 收稿日期:2019-02-14
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  • 在线发布日期: 2019-05-29
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