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通过加权基因共表达网络分析鉴定急性心肌梗死检测的生物标志物。

Biomarkers identification for acute myocardial infarction detection via weighted gene co-expression network analysis.

作者信息

Zhang Shu, Liu Weixia, Liu Xiaoyan, Qi Jiaxin, Deng Chunmei

机构信息

Department of Cardiology, Daqing People's Hospital, Daqing, Heilongjiang, China.

出版信息

Medicine (Baltimore). 2017 Nov;96(47):e8375. doi: 10.1097/MD.0000000000008375.

Abstract

The study aimed to seek potential biomarkers for acute myocardial infarction (AMI) detection and treatment.The dataset GSE48060 was used, consisting of 52 peripheral blood samples (31 AMI samples and 21 normal controls). By limma package, differentially expressed genes (DEGs) between 2 kinds of samples were identified, followed by enrichment analysis, subpathway analysis, protein-protein interaction (PPI) network analysis, and transcription factor network (TFN) analysis. Weighted gene co-expression network analysis was used to further extract key modules relating to AMI, followed by enrichment and TFN analyses. Expression validation was performed via meta-analysis of 2 datasets, GSE22229 and GSE29111.A set of 428 DEGs in AMI were screened out, and the upregulated toll-like receptor (TLR) family genes (TLR1, TLR2, and TLR10) were enriched in wound response, immune response and inflammatory response functions, and downregulated genes (GBP5, CXCL5, GZMA, CCL5, and CCL4) were correlated with immune response. CCL5, GZMA, GZMB, TLR2, and formyl peptide receptor 1 (FPR1) were predicted as crucial nodes in the PPI network. Signal transducer and activator of transcription 1 (STAT1) was the key transcription factor (TF) with multiple targets. The grey module was highly related to AMI. Genes in this module were closely related to regulation of macrophage activation, and spermatogenic leucine zipper 1 (SPZ1) was identified as a TF. Expressions of TLR2 and FPR1 were confirmed via the integrated matrix.Several potential biomarkers for AMI detection were identified, such as GZMB, GBP5, FPR1, TLR2, STAT1, and SPZ1. They might exert their functions via regulation of immune and inflammation responses. Genes in grey module play significant roles in AMI via regulation of macrophage activation.

摘要

该研究旨在寻找用于急性心肌梗死(AMI)检测和治疗的潜在生物标志物。使用了数据集GSE48060,其由52份外周血样本组成(31份AMI样本和21份正常对照)。通过limma软件包,鉴定了两种样本之间的差异表达基因(DEG),随后进行了富集分析、子通路分析、蛋白质-蛋白质相互作用(PPI)网络分析和转录因子网络(TFN)分析。使用加权基因共表达网络分析进一步提取与AMI相关的关键模块,随后进行富集和TFN分析。通过对GSE22229和GSE29111这两个数据集的荟萃分析进行表达验证。筛选出一组428个AMI中的DEG,上调的Toll样受体(TLR)家族基因(TLR1、TLR2和TLR10)在伤口反应、免疫反应和炎症反应功能中富集,而下调基因(GBP5、CXCL5、GZMA、CCL5和CCL4)与免疫反应相关。CCL5、GZMA、GZMB、TLR2和甲酰肽受体1(FPR1)被预测为PPI网络中的关键节点。信号转导和转录激活因子1(STAT1)是具有多个靶点的关键转录因子(TF)。灰色模块与AMI高度相关。该模块中的基因与巨噬细胞激活的调节密切相关,生精亮氨酸拉链1(SPZ1)被鉴定为一种TF。通过整合矩阵证实了TLR2和FPR1的表达。鉴定出了几种用于AMI检测的潜在生物标志物,如GZMB、GBP5、FPR1、TLR2、STAT1和SPZ1。它们可能通过调节免疫和炎症反应发挥作用。灰色模块中的基因通过调节巨噬细胞激活在AMI中发挥重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/740b/5708914/bc5038cb5600/medi-96-e8375-g001.jpg

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