Gene alterations in monocytes are pathogenic factors for immunoglobulin a nephropathy by bioinformatics analysis of microarray data.
Gene alterations in monocytes are pathogenic factors for immunoglobulin a nephropathy by bioinformatics analysis of microarray data.
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DOI：
10.1186/s12882-018-0944-z
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发表时间：
2018-07-20
期刊：
影响因子：
2.3
通讯作者：
Liu Z
中科院分区：
文献类型：
--
作者：
Guo Y;Gao W;Wang D;Liu W;Liu Z
免疫球蛋白A肾病（IgAN）是世界范围内最常见的原发性肾小球疾病。该研究旨在为IgAN管理提供潜在的分子生物标志物。利用公共基因表达谱GSE 58539，包含17个单核细胞样本（8个分离自IgAN患者的单核细胞样本和9个分离自健康献血员的单核细胞样本），首先通过limma包鉴定两种样本之间的差异表达基因（DEG）。之后，进行了途径富集分析。构建了蛋白质-蛋白质相互作用（PPI）网络，并利用四种网络中心性分析方法对PPI网络中的关键节点进行了预测。最后根据每个样本中的表达量构建基因功能相互作用（FI）网络，并从FI网络中提取模块网络。共筛选出678个DEG，其中72个DEG被确定为PPI网络中的关键节点，可以很好地区分IgAN和健康样本。其中，IL 6、TNF、IL 1B、PRKACA和CCL 20与造血细胞谱系、细胞凋亡和Toll样受体（TLR）信号通路密切相关。FI网络中有12个基因属于72个关键节点，如CCL 20、HDAC 10、FPR 2和PRKACA，它们也是4个模块网络中的关键基因。在IgAN患者的单核细胞中鉴定了几个关键基因，如IL 6、TNF、IL 1B、CCL 20、PRKACA、FPR 2和HDAC 10。这些基因可能共同参与IgAN进展过程中的TLR和凋亡信号通路。
Immunoglobulin A nephropathy (IgAN) is the most frequent primary glomerulopathy worldwide. The study aimed to provide potential molecular biomarkers for IgAN management. The public gene expression profiling GSE58539 was utilized, which contained 17 monocytes samples (8 monocytes samples isolated from IgAN patients and 9 monocytes samples isolated from healthy blood donors). Firstly, differentially expressed genes (DEGs) between the two kinds of samples were identified by limma package. Afterwards, pathway enrichment analysis was implemented. Thereafter, protein-protein interaction (PPI) network was constructed and key nodes in PPI network were predicted using four network centrality analyses. Ultimately, gene functional interaction (FI) was constructed according to expressions in each sample, and then module network was extracted from FI network. A total of 678 DEGs were screened out, of these, 72 DEGs were identified as crucial nodes in PPI network that could well distinguish IgAN and healthy samples. In particular, IL6, TNF, IL1B, PRKACA and CCL20 were closely related to pathways such as hematopoietic cell lineage, apoptosis and Toll-like receptor (TLR) signaling pathway. Moreover, 12 genes in the FI network belonged to the 72 identified key nodes, such as CCL20, HDAC10, FPR2 and PRKACA, which were also key genes in 4 module networks. Several crucial genes were identified in monocytes of IgAN patients, such as IL6, TNF, IL1B, CCL20, PRKACA, FPR2 and HDAC10. These genes might co-involve in pathways such as TLR and apoptosis signaling during IgAN progression.
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