生物信息学分析筛选骨关节炎关键基因的研究

Research on screening key genes of osteoarthritis by bioinformatics analysis

目的通过生物信息学研究骨关节炎(OA)和健康对照者的差异表达基因(DEGs),为诊断和治疗OA提供新的靶点。方法从GEO数据库下载基因芯片数据集GSE55457、GSE55235、GSE12021,采用GEO2R在线分析工具筛选出各数据集的DEGs并找到交集。采用DAVID在线分析工具进行GO功能富集和KEGG通路富集分析。基于STRING数据库的信息分析DEGs蛋白相互作用(PPI),使用Cytoscape软件构建PPI网络并找出hub基因。结果共筛选得到126个DEGs,GO分析发现其主要参与细胞对促肾上腺皮质激素释放激素刺激的反应、通过mRNA剪接体对mRNA的剪接、负向调控基因表达、正向调控单核细胞聚集、正向调控成纤维细胞增殖等生物学过程,KEGG主要富集在MAPK、EB病毒感染、Ⅰ型人类T细胞白血病病毒分子感染、癌症中蛋白聚糖分子、恶性肿瘤分子、破骨细胞分化、PI3K/Akt、胰岛素信号转导、肿瘤中miRNAs、ErbB、HIF-1、膀胱癌信号通路。通过STRING和Cytoscape分析构建了4个核心子网络,并发现了JUN、BTG2、ATF3、DUSP1、HNRNPA1、SF1、SRSF7、TRA2B、TRA2A、PPP1R15A 10个度值最高的hub基因。结论JUN、BTG2、ATF3、DUSP1、HNRNPA1、SF1、SRSF7、TRA2B、TRA2A、PPP1R15A基因均可能是OA发病过程中新的生物标记物。

Objective To study the differentially expressed genes(DEGs)between osteoarthritis(OA)patients and healthy control by bioinformatics,and to identify new targets for the diagnosis and treatment of OA.Methods The microarray datasets GSE55457,GSE55235 and GSE12021 were downloaded from the GEO database,and the DEGs of each dataset was screened by GEO2R online analysis tool and the intersection was found.The David online analysis tool was used for GO function enrichment and KEGG pathway enrichment analysis.Based on the information of STRING database,the protein-protein interaction(PPI)of DEGs was analyzed,and the PPI network was constructed by using Cytoscape software to find the hub genes.Results A total of 126 DEGs were screened.GO analysis showed that they were mainly involved in the biological processes,including cell response to corticotropin-releasing hormone stimulation,mRNA splicing through mRNA splicer,negative regulation of gene expression,positive regulation of monocyte aggregation and positive regulation of fibroblast proliferation,etc.KEGG was mainly enriched in MAPK,EB virus infection and human T-cell leukemia virus typeⅠinfection,proteoglycan molecular in cancer,malignant tumor molecular,osteoclast differentiation factor,PI3K/Akt,insulin signal transduction,miRNAs in tumor,ErbB,HIF-1,bladder cancer signal pathways.Four core subnetworks were constructed by STRING and Cytoscape analysis,and 10 hub genes with the highest degree were found,including JUN,BTG2,ATF3,DUSP1,HNRNPA1,SF1,SRSF7,TRA2B,TRA2A,PPP1R15A.Conclusion JUN,BTG2,ATF3,DUSP1,HNRNPA1,SF1,SRSF7,TRA2B,TRA2A and PPP1R15A may be the new biomarkers in the pathogenesis of OA.