基于生物信息学方法鉴别骨关节炎自噬的关键基因和途径

Identification of key genes and pathways for autophagy in osteoarthritis based on bioinformatics methods

目的通过生物信息学方法,探讨自噬相关基因在骨关节炎(OA)中的潜在作用。方法利用GEO数据库的GEO DataSets检索窗口以“Osteoarthritis”为关键词,数据公开日期限制为2010年1月1日至2020年1月1日,筛选得到基因微阵列数据集(GSE55457),对GSE55457数据矫正后分析获得差异表达基因(DEGs),然后利用GeneCards得到的自噬相关基因并与DEGs作交集,对交集基因作GO与KEGG富集分析和绘制蛋白质-蛋白质相互作用网络,最后得到重要模块并对其基因作KEGG富集分析和筛选出Hub关键基因。结果得到203个DEGs和5786个自噬基因,二者取交集获得65个基因,其富集在279个GO条目和44个KEGG条目;重要模块的基因主要涉及MAPK、JAK-STAT和PI3K-Akt等信号通路,关键的基因有VEGFA、JUN、CTNNB1、MYC、NR4A1、MAP2K7和DUSP1。结论基因VEGFA、JUN和CTNNB1等通过MAPK、JAK-STAT和PI3K-Akt主要途径调节自噬反应,影响OA的发生发展。

Objective To explore the potential role of autophagy related genes in osteoarthritis(OA)by bioinformatics methods.Methods Using the GEO DataSets retrieval window of the GEO database with the keyword“Osteoarthritis”,the data disclosure date was limited to January 1st,2010 to January 1st,2020.The gene microarray dataset(GSE55457)was screened,and the differentially expressed genes(DEGs)were obtained from GSE55457 after correction.Then,the autophagy related genes obtained from GeneCards were used to intersection with DEGs,and the intersection genes were performed by GO and KEGG enrichment analysis and the proteinprotein interaction network was mapped.Finally,the key modules were obtained and the key genes of Hub were screened by KEGG enrichment analysis.Results A total of 203 DEGs and 5786 autophagy genes were obtained,and 65 genes were obtained from the intersection of the two,which were enriched in 279 GO entries and 44 KEGG entries.The genes of important modules were mainly involved in MAPK,JAK-STAT,and PI3K-Akt signaling pathways,and the key genes were VEGFA,JUN,CTNNB1,MYC,NR4A1,MAP2K7,and DUSP1.Conclusion The genes VEGFA,JUN,and CTNNB1 regulate the autophagy response through the main pathways of MAPK,JAK-STAT,and PI3K-Akt,and affect the occurrence and development of OA.