Lv Jianlan, Wang Zhenwei
Department of Rehabilitation Medicine, People's Hospital of Anji, Huzhou, Zhejiang Province, China.
The Third School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China.
Medicine (Baltimore). 2025 Sep 5;104(36):e44306. doi: 10.1097/MD.0000000000044306.
Lower back pain caused by intervertebral disk degeneration (IDD) is a common problem among middle-aged and older adults. We aimed to identify novel diagnostic biomarkers of IDD and analyze the potential association between key genes and immune cell infiltration. We screened differentially expressed genes (DEGs) related to IDD and gene sets associated with mitochondrial energy metabolism using the Gene Expression Omnibus and GeneCards databases, respectively. Subsequently, we used multiple enrichment analysis methods to determine the biological functionalities of mitochondrial energy metabolism-related differentially expressed genes (MEMRDEGs). Key genes were selected using logistic regression analysis, a support vector machine algorithm, and least absolute shrinkage and selection operator regression analysis to construct an IDD diagnostic model. To obtain further insights, we examined the relationship between key genes and the presence of infiltrating immune cells. We screened 1304 DEGs that exhibited substantial differences in 20 pathways, including the Wnt signaling pathway, between the IDD and control groups. We identified 33 MEMRDEGs and selected 7 key genes (NDUFA6, YWHAZ, DLAT, BDNF, ECI2, ACO1, and ALDH7A1) to construct an IDD diagnostic model. Receiver operating characteristic curve analysis revealed that these genes exhibited high accuracy in assessing IDD risk, with BDNF and DLAT particularly distinguishing between the low- and high-risk IDD groups. Finally, using single-sample gene set enrichment analysis, we identified a relationship between IDD and immune infiltration, with most immune cells showing strong correlations. A significant positive relationship was found between ACO1 and the immune cells, known as immature dendritic cells. These results offer remarkable insights into the mechanisms underlying the occurrence and development of IDD, potentially identifying new opportunities for diagnosis and therapeutic intervention.
椎间盘退变(IDD)引起的下背部疼痛是中老年人群中的常见问题。我们旨在识别IDD的新型诊断生物标志物,并分析关键基因与免疫细胞浸润之间的潜在关联。我们分别使用基因表达综合数据库(Gene Expression Omnibus)和基因卡片数据库(GeneCards)筛选与IDD相关的差异表达基因(DEG)以及与线粒体能量代谢相关的基因集。随后,我们使用多种富集分析方法来确定线粒体能量代谢相关差异表达基因(MEMRDEG)的生物学功能。使用逻辑回归分析、支持向量机算法和最小绝对收缩和选择算子回归分析来选择关键基因,以构建IDD诊断模型。为了获得更深入的见解,我们研究了关键基因与浸润免疫细胞存在之间的关系。我们筛选出1304个DEG,这些基因在IDD组和对照组之间的20条通路(包括Wnt信号通路)中表现出显著差异。我们鉴定出33个MEMRDEG,并选择7个关键基因(NDUFA6、YWHAZ、DLAT、BDNF、ECI2、ACO1和ALDH7A1)来构建IDD诊断模型。受试者工作特征曲线分析表明,这些基因在评估IDD风险方面具有很高的准确性,其中BDNF和DLAT在区分低风险和高风险IDD组方面尤为突出。最后,使用单样本基因集富集分析,我们确定了IDD与免疫浸润之间的关系,大多数免疫细胞显示出强相关性。发现ACO1与称为未成熟树突状细胞的免疫细胞之间存在显著的正相关。这些结果为IDD发生和发展的潜在机制提供了重要见解,可能为诊断和治疗干预带来新的机会。