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动脉粥样硬化患者血液转录组中关键基因的筛选
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(江苏大学附属医院心内科,江苏省镇江市 212001)

作者简介:

玛伊拜·木沙江,硕士研究生,主要研究方向为糖尿病大血管并发症的基础与临床,E-mail:2827613727@qq.com。

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国家自然科学基金项目(81970379)


Screening of key genes from blood transcriptome of patients with atherosclerosis
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Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, China)

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    摘要:

    目的]基于血液转录组学探讨动脉粥样硬化患者血液转录组中的关键基因。 [方法]从GEO数据库中选取三个数据集GSE12288、GSE27034和GSE90074,进行合并和归一化处理,分析动脉粥样硬化患者和对照者外周血样本之间的差异基因,对差异表达基因进行富集分析,然后对所有基因进行加权基因共表达网络分析,利用差异表达基因构建蛋白质-蛋白质相互作用(PPI)网络,利用CytoHubba基于共表达网络和PPI网络筛选关键基因。通过RT-qPCR检测关键基因的表达。 [结果]在动脉粥样硬化患者和对照者之间鉴定出74个下调基因和145个上调基因,通过GO和KEGG富集分析发现其主要在中性粒细胞活化、粒细胞活化、细胞因子-细胞因子受体相互作用和趋化因子信号通路等方面显著富集。此外,还鉴定出共表达网络中的前10个基因和PPI网络中的前20个基因,其中PRF1、NKG7、GZMB和CCL5在PPI网络和共表达网络中具有较高的核心地位。RT-qPCR结果显示,与非冠状动脉动脉粥样硬化者相比,冠状动脉粥样硬化患者外周静脉血外周血单个核细胞(PBMC)中PRF1和GZMB的mRNA表达水平显著降低(P<0.05),而NKG7和CCL5的mRNA表达水平显著升高(P<0.05)。 [结论]PRF1、GZMB、NKG7和CCL5可能是动脉粥样硬化患者血液转录组中的关键基因,有望成为诊断和治疗动脉粥样硬化的潜在生物学标志。

    Abstract:

    Aim To explore the key genes in the blood transcriptome of atherosclerosis patients based on blood transcriptomics. Methods Three datasets GSE12288, GSE27034 and GSE90074 were extracted from the GEO database and performed the merging and normalization processing. The differential genes in peripheral blood samples of atherosclerosis patients and controls were analyzed, and enrichment analysis of differentially expressed genes were performed. Then weighted gene co-expression network analysis was performed for all genes. Using differentially expressed genes to construct protein-protein interaction (PPI) network, and using CytoHubba to screen key genes based on co-expression network and PPI network. And the expression levels of key genes were detected by RT-qPCR. Results 74 down-regulated genes and 145 up-regulated genes were identified between atherosclerosis patients and controls. GO and KEGG enrichment analyses revealed that they were significantly enriched in neutrophil activation, granulocyte activation, cytokine-cytokine receptor interaction and chemokine signaling pathway. In addition, the top 10 genes in the co-expression network and the top 20 genes in the PPI network were also identified, in which PRF1, NKG7, GZMB and CCL5 played a high core role in the PPI network and co-expression network. The RT-qPCR results showed that compared with the non coronary atherosclerosis controls, the mRNA expression levels of PRF1 and GZMB in peripheral venous blood peripheral blood mononuclear cell (PBMC) of coronary atherosclerosis patients were significantly reduced (P<0.05), while the mRNA expression levels of NKG7 and CCL5 were significantly increased (P<0.05). Conclusion PRF1, GZMB, NKG7 and CCL5 may be key genes in the blood transcriptome of atherosclerosis patients, and are expected to be potential biomarkers for diagnosis and treatment of atherosclerosis.

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玛伊拜·木沙江,钱勇江,王中群.动脉粥样硬化患者血液转录组中关键基因的筛选[J].中国动脉硬化杂志,2024,32(8):669~676.

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  • 收稿日期:2023-12-05
  • 最后修改日期:2024-04-29
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  • 在线发布日期: 2024-08-21
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