晚期骨关节炎软骨退行性变的生物信息学分析

Bioinformatics analysis of cartilage degeneration in advanced osteoarthritis

目的基于生物信息学方法筛选并分析晚期骨关节炎(OA)软骨退行性变相关的差异表达基因。方法选择GSE57218数据集作为分析对象,该数据集是基于GEO公共数据库进行数据检索获得。采用R语言limma工具包筛选DEmRNAs,并对数据进行标准化处理后,利用Metascape在线分析软件及R语言clusterProfiler包分别对DEmRNAs行GO功能和KEGG通路富集分析。选用String在线工具行PPI分析,将结果导入Cytoscape软件得出核心模块与预测核心基因。利用OMIM人类基因数据库筛选出与Hub基因、核心模块的共性表达基因,用GSEA富集分析筛选出核心信号通路及核心基因;将上述筛选出的基因用于预测潜在治疗药物并进行组织定位特异性分析。结果通过对GSE57218进行分析,共筛选出305个差异表达基因。对上述差异基因行GO和KEGG分析,GO功能富集分析主要富集在NABA核心基质组、ECM的组织、骨骼系统开发、基质组相关、血小板脱粒等。KEGG和GSEA功能富集分析结果显示,与OA发病相关的核心通路为ECM受体相互作用、黏附斑激酶信号通路核心基因。分别对Cytoscape、MCODE、GSEA与OMIM取交集,共筛选出7个靶向基因,PLOD1、COL5A2在平滑肌中特异性表达。结论筛选出的差异表达基因和相关信号通路有助于理解OA软骨损伤发病的分子机制,同时为临床药物治疗OA的研究提供新思路。

Objective To screen and analyze differentially expressed genes related to cartilage degeneration in advanced osteoarthritis(OA)based on bioinformatics methods.Methods GSE57218 data set was selected as analysis object,and the data set was obtained through data retrieval based on GEO public database.R language limma toolkit was used to screen DEmRNAs,and after the data were standardized,Metascape online analysis software and R language clusterProfiler package were carried out on GO function and KEGG pathway enrichment analysis of DEmRNAs,respectively.String database was selected for PPI analysis,and the results were imported into Cytoscape software to obtain core modules and predict core genes.OMIM human gene database was used to screen common expression genes with Hub genes and core modules,and GSEA enrichment analysis was used to screen core signaling pathways and core genes.And the above-mentioned selected genes were used to predict potential therapeutic drugs and conduct tissue specific analysis.Results A total of 305 differentially expressed genes were screened by GSE57218 analysis.GO and KEGG analysis were performed for these differentially expressed genes.GO functional enrichment analysis was mainly concentrated in NABA core matrix group,ECM tissue,skeletal system development,matrix group correlation and platelet threshing,etc.The results of KEGG and GSEA functional enrichment analysis showed that the core pathways related to the pathogenesis of OA were ECM receptor interaction and core genes of the focal adhesion kinase signaling pathway.Intersection among Cytoscape,MOCDE,GSEA and OMIM were respectively obtained to select 7 targeted genes,and PLOD1 and COL5A2 were expressed specifically in smooth muscle.Conclusion Selected differential genes and related signaling pathways are helpful to understand the molecular mechanism of OA cartilage injury and provide new ideas for clinical drug treatment of OA.