Comprehensive analysis of mitochondrial energy metabolism-related genes and immune infiltration in intervertebral disk degeneration

椎间盘退变中线粒体能量代谢相关基因和免疫浸润的综合分析

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Abstract

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.

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