Institute of Biomedical Engineering, Kunming Medical Univesity, Kunming 650500, China.
Department of Science and Technology, Kunming Medical University, Kunming 650500, China.
Int J Mol Sci. 2024 Jul 10;25(14):7551. doi: 10.3390/ijms25147551.
Multiple sclerosis (MS) is a chronic disease characterized by inflammation and neurodegeneration of the central nervous system. Despite the significant role of oxidative stress in the pathogenesis of MS, its precise molecular mechanisms remain unclear. This study utilized microarray datasets from the GEO database to analyze differentially expressed oxidative-stress-related genes (DE-OSRGs), identifying 101 DE-OSRGs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicate that these genes are primarily involved in oxidative stress and immune responses. Through protein-protein interaction (PPI) network, LASSO regression, and logistic regression analyses, four genes (, , , and ) were identified as being closely related to MS. A diagnostic prediction model based on logistic regression demonstrated good predictive power, as shown by the nomogram curve index and DAC results. An immune-cell infiltration analysis using CIBERSORT revealed significant correlations between these genes and immune cell subpopulations. Abnormal oxidative stress and upregulated expression of key genes were observed in the blood and brain tissues of EAE mice. A molecular docking analysis suggested strong binding potentials between the proteins of these genes and several drug molecules, including isoquercitrin, decitabine, benztropine, and curcumin. In conclusion, this study identifies and validates potential diagnostic biomarkers for MS, establishes an effective prediction model, and provides new insights for the early diagnosis and personalized treatment of MS.
多发性硬化症(MS)是一种以中枢神经系统炎症和神经退行性病变为特征的慢性疾病。尽管氧化应激在 MS 的发病机制中具有重要作用,但它的确切分子机制仍不清楚。本研究利用 GEO 数据库中的微阵列数据集,分析了差异表达的氧化应激相关基因(DE-OSRGs),鉴定出 101 个 DE-OSRGs。基因本体论(GO)和京都基因与基因组百科全书(KEGG)分析表明,这些基因主要参与氧化应激和免疫反应。通过蛋白质-蛋白质相互作用(PPI)网络、LASSO 回归和逻辑回归分析,确定了四个与 MS 密切相关的基因(、、、和)。基于逻辑回归的诊断预测模型显示出良好的预测能力,表现在列线图曲线指数和 DAC 结果上。使用 CIBERSORT 进行的免疫细胞浸润分析表明,这些基因与免疫细胞亚群之间存在显著相关性。EAE 小鼠的血液和脑组织中观察到异常的氧化应激和关键基因的上调表达。分子对接分析表明,这些基因的蛋白质与几种药物分子(包括异槲皮苷、地西他滨、苯扎托品和姜黄素)之间具有很强的结合潜力。总之,本研究确定并验证了 MS 的潜在诊断生物标志物,建立了有效的预测模型,为 MS 的早期诊断和个性化治疗提供了新的见解。