Abstract：
Background and Objectives. Glucocorticoid-induced osteonecrosis of the femoral head (GIONFH) is a serve complication of long-term administration of glucocorticoids. Previous experimental studies have shown that ferroptosis might be involved in the pathological process of GIONFH. The purpose of this study is to identify the ferroptosis-related genes and pathways of GIONFH by bioinformatics to further illustrate the mechanism of ferroptosis in SONFH through bioinformatics analysis. Materials and Methods. The GSE123568 mRNA expression profile dataset, including 30 GIONFH samples and 10 non-GIONFH samples, was downloaded from the Gene Expression Omnibus (GEO) database. Ferroptosis-related genes were obtained from the FerrDb database. First, differentially expressed genes (DEGs) were identified between the serum samples from GIONFH cases and those from controls. Ferroptosis-related DEGs were obtained from the intersection of ferroptosis-related genes and DEGs. Only ferroptosis DEGs were used for all analyses. Then, we conducted a Kyoto encyclopedia of genome (KEGG) and gene ontology (GO) pathway enrichment analysis. We constructed a protein-protein interaction (PPI) network to screen out hub genes. Additionally, the expression levels of the hub genes were validated in an independent dataset GSE10311. Results. A total of 27 ferroptosis-related DEGs were obtained between the peripheral blood samples of GIONFH cases and non-GIONFH controls. Then, GO, and KEGG pathway enrichment analysis revealed that ferroptosis-related DEGs were mainly enriched in the regulation of the apoptotic process, oxidation-reduction process, and cell redox homeostasis, as well as HIF-1, TNF, FoxO signaling pathways, and osteoclast differentiation. Eight hub genes, including TLR4, PTGS2, SNCA, MAPK1, CYBB, SLC2A1, TXNIP, and MAP3K5, were identified by PPI network analysis. The expression levels of TLR4, TXNIP and MAP3K5 were further validated in the dataset GSE10311. Conclusion. A total of 27 ferroptosis-related DEGs involved in GIONFH were identified via bioinformatics analysis. TLR4, TXNIP, and MAP3K5 might serve as potential biomarkers and drug targets for GIONFH.
摘要：
背景和目标。糖皮质激素诱导的股骨头坏死（GIONFH）是长期使用糖皮质激素的并发症。先前的实验研究表明，铁性凋亡可能参与了GIONFH的病理过程。本研究的目的是通过生物信息学鉴定GIONFH的铁凋亡相关基因和途径，通过生物信息学分析进一步阐明SONFH铁凋亡的机制。材料和方法。GSE123568mRNA表达谱数据集，包括30个GIONFH样本和10个非GIONFH样本，从基因表达综合(GEO)数据库下载。从FerrDb数据库获得铁凋亡相关基因。首先,在来自GIONFH病例的血清样品和来自对照的血清样品之间鉴定了差异表达基因(DEGs)。从与铁凋亡相关的基因和DEGs的交集获得与铁凋亡相关的DEGs。仅将铁凋亡DEGs用于所有分析。然后，我们进行了京都百科全书基因组(KEGG)和基因本体论(GO)途径富集分析。我们构建了一个蛋白质-蛋白质相互作用（PPI）网络来筛选出集线器基因。此外,在独立的数据集GSE10311中验证了hub基因的表达水平.结果。在GIONFH病例和非GIONFH对照的外周血样本之间总共获得了27个与铁凋亡相关的DEGs。然后，GO,和KEGG途径富集分析显示，铁凋亡相关的DEGs主要富集在凋亡过程的调节中，氧化还原过程，和细胞氧化还原稳态，以及HIF-1，TNF，FoxO信号通路,和破骨细胞分化。八个枢纽基因，包括TLR4、PTGS2、SNCA、MAPK1,CYBB,SLC2A1、TXNIP、和MAP3K5，通过PPI网络分析鉴定。在数据集GSE10311中进一步验证TLR4、TXNIP和MAP3K5的表达水平。结论。通过生物信息学分析，共鉴定出27个参与GIONFH的铁凋亡相关DEGs。TLR4、TXNIP、和MAP3K5可能作为GIONFH的潜在生物标志物和药物靶标。
