Xia Yushuang, Wang Bo, Pan Pengfei, Ren Xiangshun, Gao Lixi, Xiong Jian, Ma Yan
The First Clinical College of Hubei University of Chinese Medicine, Wuhan 430061, China.
Rehabilitation Medicine Center, Wuhan First Municipal Hospital Affiliated to Hubei University of Chinese Medicine, Wuhan 430022, China.
Zhejiang Da Xue Xue Bao Yi Xue Ban. 2024 Dec 25;53(6):680-690. doi: 10.3724/zdxbyxb-2024-0089.
To explore ferroptosis-related genes in osteoporosis through bioinformatic analysis and study.
Osteoporosis-related genes were identified from dataset GSE35958 in the Gene Expression Omnibus database; and the ferroptosis-related genes were identified from the FerrDb database. These were intersected with the differentially expressed genes in GSE35958 to obtain ferroptosis-related genes in osteoporosis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed for the differentially expressed genes. And Spearman correlation and protein-protein interaction network analysis were performed. Then, the hub genes of ferroptosis in osteoporosis were screened by Degree, MNC, EPC, MCC and DMNC in Cytoscape software CytoHubba plugin; and analyzed with receiver operating characteristic (ROC) curves. The bone marrow mesenchymal stem cells from osteoporosis patients (osteoporosis group) and non-osteoporosis patients (control group) were subjected to quantitative reverse transcription polymerase chain reaction to detect the messenger RNA expression of ferroptosis hub genes in both groups.
A total of 32 differentially expressed genes related to ferroptosis in osteoporosis were identified, including 26 up-regulated genes and 6 down-regulated genes. GO enrichment analysis showed that the identified genes were mainly involved in intercellular adhesion, lipid metabolism and cytokine response. KEGG enrichment analysis showed that the genes were mainly involved in signaling pathways of adhesive plaques, MAPK, PI3K-Akt, and Wnt. Spearman correlation analysis showed correlation among differentially expressed genes. Six hub genes for ferroptosis in osteoporosis were obtained, namely , , , , , and -. ROC curve analysis showed that these hub genes had good diagnostic performance in osteoporosis and may become potential biomarkers of osteoporosis. experiments confirmed significant differences in these hub genes between the control group and the osteoporosis group (all <0.05).
This study has identified six ferroptosis-related hub genes in osteoporosis, which may be used as novel biomarkers for the early diagnosis and treatment of osteoporosis.
通过生物信息学分析和研究探索骨质疏松症中与铁死亡相关的基因。
从基因表达综合数据库中的数据集GSE35958中鉴定出骨质疏松症相关基因;并从FerrDb数据库中鉴定出铁死亡相关基因。将这些基因与GSE35958中的差异表达基因进行交集分析,以获得骨质疏松症中与铁死亡相关的基因。对差异表达基因进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析。并进行Spearman相关性分析和蛋白质-蛋白质相互作用网络分析。然后,通过Cytoscape软件的CytoHubba插件中的Degree、MNC、EPC、MCC和DMNC筛选骨质疏松症中铁死亡的枢纽基因;并用受试者工作特征(ROC)曲线进行分析。对骨质疏松症患者(骨质疏松组)和非骨质疏松症患者(对照组)的骨髓间充质干细胞进行定量逆转录聚合酶链反应,以检测两组中铁死亡枢纽基因的信使核糖核酸表达。
共鉴定出32个骨质疏松症中与铁死亡相关的差异表达基因,其中上调基因26个,下调基因6个。GO富集分析表明,鉴定出的基因主要参与细胞间黏附、脂质代谢和细胞因子反应。KEGG富集分析表明,这些基因主要参与黏着斑、丝裂原活化蛋白激酶(MAPK)、磷脂酰肌醇-3激酶-蛋白激酶B(PI3K-Akt)和Wnt信号通路。Spearman相关性分析显示差异表达基因之间存在相关性。获得了骨质疏松症中铁死亡的6个枢纽基因,即 、 、 、 、 、 和 。ROC曲线分析表明,这些枢纽基因在骨质疏松症中具有良好的诊断性能,可能成为骨质疏松症的潜在生物标志物。 实验证实对照组和骨质疏松组之间这些枢纽基因存在显著差异(均<0.05)。
本研究在骨质疏松症中鉴定出6个与铁死亡相关的枢纽基因,它们可能作为骨质疏松症早期诊断和治疗的新型生物标志物。