Osteonecrosis of the femoral head (ONFH) is a condition caused by a disruption or damage to the femoral head's blood supply, which causes the death of bone cells and bone marrow components and prevents future regeneration. Ferroptosis, a type of controlled cell death, is caused by iron-dependent lipid peroxidation. Here, we identified ferroptosis-related genes and infiltrating immune cells involved in ONFH and predicted the underlying molecular mechanisms. The GSE123568 dataset was subjected to differential expression analysis to identify genes related to ferroptosis. Subsequently, GO and KEGG pathway enrichment analyses, as well as protein–protein interaction (PPI) network analysis, were conducted. Hub genes involved in ferroptosis were identified using machine learning and other techniques. Additionally, immune infiltration analysis and lncRNA–miRNA-mRNA network prediction analysis were performed. Finally, we determined whether ferroptosis occurred by measuring iron content. The hub genes were validated by ROC curve analysis and qRT–PCR. Four ferroptosis-related hub genes (MAPK3, PTGS2, STK11, and SLC2A1) were identified. Additionally, immune infiltration analysis revealed a strong correlation among ONFH, hub genes, and various immune cells. Finally, we predicted the network relationship between differentially expressed lncRNAs and hub genes in the lncRNA–miRNA–mRNA network. MAPK3, PTGS2, STK11, and SLC2A1 have been identified as potential ferroptosis-related biomarkers and drug targets for the diagnosis and prognosis of ONFH, while some immune cells, as well as the interaction between lncRNA, miRNA, and mRNA, have also been identified as potential pathogenesis markers and therapeutic targets.

中文翻译：

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机器学习介导的股骨头坏死铁死亡相关基因的识别

股骨头坏死 (ONFH) 是一种因股骨头血液供应中断或损坏而引起的疾病，会导致骨细胞和骨髓成分死亡并阻止未来的再生。铁死亡是一种受控细胞死亡，是由铁依赖性脂质过氧化引起的。在这里，我们鉴定了与 ONFH 相关的铁死亡相关基因和浸润免疫细胞，并预测了潜在的分子机制。对 GSE123568 数据集进行差异表达分析，以确定与铁死亡相关的基因。随后，进行了 GO 和 KEGG 通路富集分析，以及蛋白质-蛋白质相互作用（PPI）网络分析。使用机器学习和其他技术鉴定了参与铁死亡的中心基因。此外，还进行了免疫浸润分析和lncRNA-miRNA-mRNA网络预测分析。最后，我们通过测量铁含量来确定是否发生铁死亡。通过 ROC 曲线分析和 qRT-PCR 验证中心基因。确定了四个与铁死亡相关的中枢基因（MAPK3、PTGS2、STK11 和 SLC2A1）。此外，免疫浸润分析显示 ONFH、中枢基因和各种免疫细胞之间存在很强的相关性。最后，我们预测了lncRNA-miRNA-mRNA网络中差异表达的lncRNA和中心基因之间的网络关系。MAPK3、PTGS2、STK11和SLC2A1已被确定为潜在的铁死亡相关生物标志物和用于ONFH诊断和预后的药物靶点，同时一些免疫细胞以及lncRNA、miRNA和mRNA之间的相互作用也已被确定作为潜在的发病标志物和治疗靶点。