激素性股骨头坏死中的PTGS2和STAT3:潜在铁死亡相关诊断生物标志物  

PTGS2 and STAT3 in steroid-induced osteonecrosis of the femoral head:ferroptosis-related potential diagnostic biomarkers

作　　者：梁学振 骆帝 李嘉程 温明韬 张建 许波 李刚[1,2] Liang Xuezhen;Luo Di;Li Jiacheng;Wen Mingtao;Zhang Jian;Xu Bo;Li Gang(First Clinical Medical School,Shandong University of Traditional Chinese Medicine,Jinan 250355,Shandong Province,China;Department of Orthopedic Microsurgery,Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Jinan 250014,Shandong Province,China)

机构地区：[1]山东中医药大学第一临床医学院,山东省济南市250355 [2]山东中医药大学附属医院显微骨科,山东省济南市250014

出　　处：《中国组织工程研究》2023年第36期5898-5904,共7页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金资助项目(82205154),项目负责人:梁学振;山东省自然科学基金青年项目(ZR2021QH004),项目负责人:梁学振;济南市临床医学科技创新计划(202019056),项目负责人:梁学振;山东省中医药科技项目(2020Q009),项目负责人:梁学振。

摘　　要：背景:研究推测铁死亡可能参与了激素性股骨头坏死的病理过程,但铁死亡在激素性股骨头坏死中的发病机制尚不清楚。目的:旨在通过生物信息学手段分析激素性股骨头坏死进展过程中调控铁死亡相关的关键基因,以进一步阐明铁死亡在激素性股骨头坏死中的生物学机制。方法:从基因表达综合数据库(GEO)下载血清来源的GSE123568数据集,包括10个非激素性股骨头坏死(类固醇给药后)样本和30个激素性股骨头坏死样本;从FerrDb数据库整理铁死亡相关基因。通过将GSE123568数据集与铁死亡基因集映射,筛选激素性股骨头坏死中铁死亡相关的差异基因,通过“clusterProfiler”R包分析差异基因的基因本体论(GO)和京都基因和基因组百科全书(KEGG)通路富集,通过“corrplot”R包分析差异基因的Spearman相关系数,通过STRING数据库构建蛋白质-蛋白质相互作用(PPI)网络,通过MCODE插件权重分析以识别重要的基因簇模块,通过CytoHubba插件利用拓扑网络算法筛选Hub基因,通过“pROC”R包分析Hub基因的ROC曲线;借助髋关节软骨来源的GSE74089数据集验证Hub基因的表达水平。结果与结论:(1)根据调整后的P值<0.01和|log2 FC|>log21.5的既定标准,在非激素性股骨头坏死和激素性股骨头坏死患者的外周血样本中筛选出30个激素性股骨头坏死中铁死亡相关的差异基因,包括20个上调基因和10个下调基因;(2)GO和KEGG通路富集分析表明,差异基因主要富集在氧化应激、缺氧诱导因子1信号通路和铁死亡;Spearman相关性分析显示差异基因之间存在一定的相关性;(3)PPI网络揭示差异基因在生物系统中具有相互作用关系,通过MCODE插件识别出2个重要的基因簇模块,通过CytoHubba插件的MCC,MNC,DMNC,Degree和EPC算法交叉映射确定7个Hub基因;(4)ROC曲线表明与非激素性股骨头坏死样本相比,Hub基因在激素性股骨头坏死样本中具有更高的诊断价�BACKGROUND:Previous experimental studies have shown that ferroptosis might be involved in the pathological process of steroid-induced osteonecrosis of the femoral head,but the pathogenesis of ferroptosis in steroid-induced osteonecrosis of the femoral head remains unclear.OBJECTIVE:To analyze the key potential ferroptosis-related genes involved in steroid-induced osteonecrosis of the femoral head to further clarify the biological mechanism of ferroptosis in steroid-induced osteonecrosis of the femoral head by bioinformatics.METHODS:The GSE123568 mRNA expression profile dataset,including 10 non-steroid-induced osteonecrosis of the femoral head(following steroid administration)samples and 30 steroid-induced osteonecrosis of the femoral head samples,was downloaded from the Gene Expression Omnibus(GEO)database.Ferroptosis-related genes were obtained from the Human Ferroptosis Database(FerrDb).The ferroptosis-related genes involved in steroid-induced osteonecrosis of the femoral head were screened by intersecting the GSE123568 dataset with the set of ferroptosis genes.The differentially expressed ferroptosis-related genes involved in steroid-induced osteonecrosis of the femoral head were identified with R software.In addition,Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses of the differentially expressed ferroptosis-related genes involved in steroidinduced osteonecrosis of the femoral head were conducted by“clusterProfiler”R package.Spearman correlations between the expression levels of the differentially expressed ferroptosis-related genes involved in steroid-induced osteonecrosis of the femoral head were confirmed with“corrplot”R package.Moreover,the protein-protein interaction(PPI)network was analyzed by using the Search Tool for the Retrieval of Interacting Genes(STRING);significant gene cluster modules were identified with the MCODE Cytoscape plugin,and hub genes among the differentially expressed ferroptosis-related genes involved in steroid-induced osteonecr

关 键 词：激素性股骨头坏死 铁死亡 生物信息学 氧化应激 生物标志物 

分 类 号：R459.9[医药卫生—治疗学] R394.2[医药卫生—临床医学] R542.2