骨性关节炎软骨下骨改变中的潜在生物标志物

Potential biomarkers in subchondral bone changes in osteoarthritis

目的通过生物信息学分析骨性关节炎(OA)软骨下骨改变过程中的潜在生物标志物及相关通路。方法从基因表达数据库(GEO)下载GSE51588数据集,鉴定差异表达基因(DEGs)并进行富集分析。构建蛋白互作网络(PPI),模块分析并筛选Hub基因。预测Hub基因的靶向MicroRNAs(miRNAs),鉴定关键miRNAs并绘制其受试者工作特征(ROC)曲线。结果最终鉴定出与OA软骨下骨改变相关的10个Hub基因,3-磷酸甘油醛脱氢酶(GAPDH)、白蛋白(ALB)、骨髓肿瘤细胞(MYC)、Toll样受体2(TLR2)、髓过氧化物酶(MPO)、中性粒细胞表达的弹性蛋白酶(ELANE)、甲酰肽受体2(FPR2)、精氨酸酶1(ARG1)、前血小板碱性蛋白(PPBP)、甲酰肽受体1(FPR1),及8个关键miRNAs(hsa-miR-6809-3p、hsa-miR-4263、hsa-miR-6759-5p、hsa-miR-6165、hsa-miR-6754-5p、hsa-miR-5588-5p、hsa-miR-877-3p、hsa-miR-4270)。结论本研究结果显示的潜在生物标志物及相关通路为OA的诊断和治疗研究提供候选靶点。

Objective Bioinformatics analysis of potential biomarkers and related pathways in the process of subchondral bone changes in osteoarthritis(OA).Methods The GSE51588 dataset was downloaded from Gene Expression Omnibus(GEO)to identify differentially expressed genes(DEGs)and perform enrichment analysis.A protein-protein interaction network(PPI)was constructed,module analysis was done and Hub genes were screened.The targeted microRNAs(miRNAs)of Hub gene were predicted.The key miRNAs were identified and their receiver operating characteristic(ROC)curve was drawn.Results Finally,10 Hub genes[glyceraldehyde-3-phosphate dehydrogenase(GAPDH),albumin(ALB),myelocytomatosis(MYC),Toll like receptor 2(TLR2),myeloperoxidase(MPO),elastase,neutrophil expressed(ELANE),formyl peptide receptor 2(FPR2),arginase 1(ARG1),pro-platelet basic protein(PPBP),formyl peptide receptor 1(FPR1)]and 8 key miRNAs(hsa-miR-6809-3p,hsa-miR-4263,hsa-miR-6759-5p,hsa-miR-6165,hsa-miR-6754-5p,hsa-miR-5588-5p,hsa-miR-877-3p,hsa-miR-4270)related to OA subchondral bone changes were identified.Conclusion The potential biomarkers and related pathways discovered in this study provide candidate targets for the diagnosis and treatment of OA.