Guo Yingbo, Gao Wenfeng, Wang Danyang, Liu Weijing, Liu Zhongjie
Department of Nephropathy, Dongfang Hospital Affiliated to Beijing University of Chinese Medicine, Beijng, 100078, China.
Department of Urology, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijng, 100700, China.
BMC Nephrol. 2018 Jul 20;19(1):184. doi: 10.1186/s12882-018-0944-z.
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.
免疫球蛋白A肾病（IgAN）是全球最常见的原发性肾小球疾病。本研究旨在为IgAN的治疗提供潜在的分子生物标志物。
利用公开的基因表达谱GSE58539，其中包含17个单核细胞样本（8个从IgAN患者中分离的单核细胞样本和9个从健康献血者中分离的单核细胞样本）。首先，使用limma软件包鉴定两种样本之间的差异表达基因（DEG）。随后，进行通路富集分析。之后，构建蛋白质-蛋白质相互作用（PPI）网络，并使用四种网络中心性分析预测PPI网络中的关键节点。最后，根据每个样本中的表达构建基因功能相互作用（FI），然后从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，能够很好地区分IgAN和健康样本。特别是，IL6、TNF、IL1B、PRKACA和CCL20与造血细胞谱系、凋亡和Toll样受体（TLR）信号通路等通路密切相关。此外，FI网络中的12个基因属于72个已鉴定的关键节点，如CCL20、HDAC10、FPR2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出了几个关键基因，如IL6、TNF、IL1B、CCL20、PRKACA、FPR2和HDAC10。这些基因可能在IgAN进展过程中共同参与TLR和凋亡信号等通路。
