基于GEO数据库对糖尿病肾病关键基因的筛选及生物信息学分析  

Identification and Bioinformatics Analysis of Key Genes in Diabetic Kidney Disease Based on GEO Database

作　　者：周任 胡雪梅 张永[1] ZHOU Ren;HU Xue-mei;ZHANG Yong(Department of Nephrology,Taihe Hospital,Hubei University of Medicine,Shiyan,Hubei 442000,China)

机构地区：[1]湖北医药学院附属太和医院肾内科,湖北十堰442000

出　　处：《湖北医药学院学报》2023年第1期40-46,51,共8页Journal of Hubei University of Medicine

摘　　要：目的:糖尿病肾病(DKD)是继发性肾病主要病因之一,正在成为全球终末期肾病的主要原因,其潜在发病机制及关键基因有待深入探索,本研究旨在进一步探讨其发病的关键基因。方法:从高通量功能基因组数据库(GEO)中获取DKD肾小球相关表达数据集GSE30528和GSE96804,筛选两个数据集共有的差异性基因。通过基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路分析上述差异基因的生物学作用。利用STRING数据库构建蛋白互作网络(PPI),并筛选关键基因。通过Nephroseq数据库对关键基因进行验证,分析与DKD临床特征的相关性。结果:数据集GSE30528和GSE96804筛出共有差异基因64个,其中包含41个表达上调基因和23个表达下调基因。GO富集主要集中在非膜结合细胞器组件、上皮细胞发育、内吞囊泡、质膜外侧及GTP酶结合等。本KEGG信号通路分析主要涉及的信号通路见于吞噬体(phagosome)、PPAR信号通路(PPAR signaling pathway)及胆固醇代谢(cholesterol metabolism)等方面。PPI网络筛选前10个关键基因为VSIG4、MS4A4A、CD163、MRC1、FOLR2、FOS、SPP1、MS4A6A、MMP7及SOX9,其中CD163、FOLR2、MS4A4A及MS4A6A的mRNA表达与DKD患者的血肌酐(SCr)水平呈正相关性。结论:DKD的发病机制涉及到多种生物学过程及多种信号通路,VSIG4、MMP7、CD163、FOLR2、MS4A4A、MS4A6A等差异性基因可能参与了DKD的发生发展。Objective Diabetic kidney disease(DKD)is one of the main causes of secondary renal disease and is becoming the main cause of end-stage renal disease worldwide.Its potential pathogenesis and key genes need to be further explored.The purpose of this study is to further explore the key genes of its pathogenesis.Methods The DKD-related expression datasets GSE30528 and GSE96804 were obtained from the gene expression omnibus(GEO)to screen the different genes shared by the two datasets.The biological effects of the above differential genes were analyzed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG).Protein-interaction network(PPI)was constructed by using STRING database,and key genes were screened.The key genes were verified by the Nephroseq database,and the correlation with the clinical features of DKD was analyzed.Results A total of 64 differential genes were screened by GSE30528 and GSE96804,including 41 up-regulated genes and 23 down-regulated genes.GO enrichment was mainly concentrated in non-membrane-bounded organelle assembly,epithelial cell development,endocytosis vesicles,outer plasma membrane and GTP enzyme binding.The signal pathways involved in this KEGG signal pathway analysis were mainly found in Phagosome,PPAR signal pathway and cholesterol metabolism.The top 10 key genes screened by PPI network were VSIG4,MS4A4A,CD163,MRC1,FOLR2,FOS,SPP1,MS4A6A,MMP7 and SOX9.The mRNA expression of CD163,FOLR2,MS4A4A and MS4A6A was positively correlated with the level of serum creatinine(SCr)in DKD patients.Conclusion The pathogenesis of DKD involves a variety of biological processes and multiple signaling pathways,and differential genes such as VSIG4,MMP7,CD163,FOLR2,MS4A4A,MS4A6A may be involved in the development of DKD.

关 键 词：糖尿病肾病 GEO 差异基因 生物信息学 

分 类 号：R587.2[医药卫生—内分泌] R692.9[医药卫生—内科学]