Department of Orthopaedics, Peking University Third Hospital, Beijing, China.
Beijing Key Laboratory of Spinal Disease Research, Beijing, China.
Front Endocrinol (Lausanne). 2023 Feb 6;14:1089796. doi: 10.3389/fendo.2023.1089796. eCollection 2023.
Lower back pain (LBP) is a leading cause of disability in the elderly and intervertebral disc degeneration (IDD) is the major contributor to LBP. Ferroptosis is a newly discovered programmed cell death, characterized by iron-dependent lethal lipid peroxidation. Growing evidence has shown that ferroptosis plays important roles in various human diseases. However, the underlying mechanism of ferroptosis in IDD remains elusive. This study is aimed to uncover the key roles of ferroptosis in the pathogenesis and progression of IDD comprehensively. To investigate the ferroptosis related differentially expressed genes (FRDEGs) in IDD, we analyzed the microarray data from the Gene Expression Omnibus (GEO) database. Then we performed functional enrichment analysis and protein-protein interaction (PPI) network analysis, and screened out the hub FRDEGs. To further evaluate the predictive value of these hub FRDEGs, we performed ROC analysis based on the GSE124272 dataset. A total of 80 FRDEGs were identified, including 20 downregulated and 60 upregulated FRDEGs. The FRDEGs were primarily involved in the biological processes of response to chemical, and response to stress. KEGG pathway enrichment analysis showed that the FRDEGs were mainly involved in ferroptosis, TNF signaling pathway, HIF-1 signaling pathway, NOD-like receptor signaling pathway, and IL-17 signaling pathway. Ten hub OSRDEGs were obtained according to the PPI analysis, including . The ROC analysis and RT-qPCR validation results suggested that most of the hub FRDEGs might be potential signature genes for IDD. This study reveals that ferroptosis might provide promising strategy for the diagnosis and treatment of IDD.
下腰痛（LBP）是老年人残疾的主要原因，椎间盘退变（IDD）是 LBP 的主要原因。铁死亡是一种新发现的程序性细胞死亡，其特征是铁依赖性致命脂质过氧化。越来越多的证据表明，铁死亡在各种人类疾病中发挥重要作用。然而，IDD 中铁死亡的潜在机制仍不清楚。本研究旨在全面揭示铁死亡在 IDD 发病机制和进展中的关键作用。为了研究 IDD 中的铁死亡相关差异表达基因（FRDEGs），我们分析了基因表达综合数据库（GEO）中的微阵列数据。然后，我们进行了功能富集分析和蛋白质-蛋白质相互作用（PPI）网络分析，并筛选出关键的 FRDEGs。为了进一步评估这些关键 FRDEGs 的预测价值，我们基于 GSE124272 数据集进行了 ROC 分析。共鉴定出 80 个 FRDEGs，包括 20 个下调和 60 个上调的 FRDEGs。FRDEGs 主要参与了对化学物质的反应和对压力的反应等生物学过程。KEGG 通路富集分析表明，FRDEGs 主要参与铁死亡、TNF 信号通路、HIF-1 信号通路、NOD 样受体信号通路和 IL-17 信号通路。根据 PPI 分析，得到了 10 个关键的 OSRDEGs，包括 。ROC 分析和 RT-qPCR 验证结果表明，大多数关键 FRDEGs 可能是 IDD 的潜在特征基因。本研究表明，铁死亡可能为 IDD 的诊断和治疗提供有前景的策略。
