骨关节炎的潜在生物标志物筛选及关键基因验证  

Screening of Potential Biomarkers and Validation of Key Genes in Osteoarthritis

作　　者：朱义芳 郭莉[1,2] 陈露 王磊 李敏[1,2] 黄玉霞[1,2] 梁翼[1,2] Zhu Yifang;Guo Li;Chen Lu(Clinical Laboratory,Department of Rheumatoid Osteoarthropathy,Sichuan Orthopaedic Hospital,Chengdu,Sichuan 610041,China)

机构地区：[1]四川省骨科医院检验科,四川成都610041 [2]四川省骨科医院风湿骨关节病科,四川成都610041

出　　处：《四川医学》2021年第10期969-975,共7页Sichuan Medical Journal

基　　金：四川省干部保健课题(编号:川干研2020-602,川干研2020-607)。

摘　　要：目的本研究旨在通过生物信息学分析确定骨关节炎滑膜组织中的关键生物标志物。方法从GEO数据库中下载GSE12021、GSE55235和GSE55457,通过Bioconductor的LIMMA包鉴定差异表达的基因(DEGs),并进行功能富集分析。使用STRING构建蛋白质-蛋白质相互作用网络(PPI),用Cytoscape进行模块分析,筛选出关键基因,并在芯片数据集中验证表达情况。结果分析基因芯片GSE12021和GSE55235骨关节炎和正常对照组之间滑膜组织差异表达的基因并取交集,获得18个表达上调基因,43个表达下调基因;GO与KEGG分析发现差异基因富集在维生素C代谢、白介6信号通路等多个骨关节炎发生发展的重要通路;通过构建PPI网络筛选出了包括促进软骨细胞破坏、调节炎症、调节软骨稳态、调控软骨基质代谢的十个关键基因,在三个表达谱数据中验证了关键基因的表达。结论骨性关节炎与正常对照之间的关键基因分析可为理解骨性关节炎的发生发展和开辟新的基因治疗手段提供新的见解。Objective To identify key biomarkers in synovial tissue of osteoarthritis by bioinformatics analysis.Methods GSE12021,GSE55235 and GSE55457 were downloaded from GEO database,and the differentially expressed genes(DEGs)were identified by LIMMA package in Bioconductor,followed by the functional enrichment analysis.Protein-protein interaction network(PPI)was established by String,the key genes were screened by Cytoscape module analysis,and the expression of which was verified in the on-chip data sets.Results The genes that were differentially expressed in synovial tissue between osteoarthritis and normal control group were analyzed and intersected.18 up-regulated genes and 43 down-regulated genes were obtained.GO and KEGG analysis showed that the differential genes were enriched in vitamin C metabolism,interleukin 6 signaling pathways and other important pathways for the development of osteoarthritis.Ten key genes were screened out by constructing PPI network,including genes that promoted chondrocyte destruction,regulated inflammation,cartilage homeostasis,and cartilage matrix metabolism.The expression of key genes was verified in three expression profile data.Conclusion Key genes analysis between osteoarthritis and normal controls may provide new insights into the pathogenesis and development of osteoarthritis and new gene therapy approaches.

关 键 词：骨关节炎 滑膜 关键基因 生物信息学分析 

分 类 号：R684.3[医药卫生—骨科学]