Xie Yongzhi, Luo Ximei, He Haiqing, Tang Min
Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha, China.
School of Computer Science and Technology, Harbin Institute of Technology, Harbin, China.
Front Neurosci. 2021 Apr 30;15:657465. doi: 10.3389/fnins.2021.657465. eCollection 2021.
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive degeneration of motor neurons. The causative pathogenic mechanisms in ALS remain unclear, limiting the development of treatment strategies. Neuroinflammation and immune dysregulation were involved in the disease onset and progression of several neurodegenerative disorders, including ALS. In this study, we carried out a bioinformatic analysis using publicly available datasets from Gene Expression Omnibus (GEO) to investigate the role of immune cells and genes alterations in ALS. Single-sample gene set enrichment analysis revealed that the infiltration of multiple types of immune cells, including macrophages, type-1/17 T helper cells, and activated CD4 + /CD8 + T cells, was higher in ALS patients than in controls. Weighted gene correlation network analysis identified immune genes associated with ALS. The Gene Ontology analysis revealed that receptor and cytokine activities were the most highly enriched terms. Pathway analysis showed that these genes were enriched not only in immune-related pathways, such as cytokine-cytokine receptor interaction, but also in PI3K-AKT and MAPK signaling pathways. Nineteen immune-related genes (, , , , , , , , , , , , , , , , , , and ) were identified as hub genes based on least absolute shrinkage and selection operator analysis. This gene signature could differentiate ALS patients from non-neurological controls ( < 0.001) and predict disease occurrence (AUC = 0.829 in training set; AUC = 0.862 in test set). In conclusion, our study provides potential biomarkers of ALS for disease diagnosis and therapeutic monitoring.
肌萎缩侧索硬化症（ALS）是一种致命的神经退行性疾病，其特征是运动神经元进行性退化。ALS的致病机制尚不清楚，这限制了治疗策略的发展。神经炎症和免疫失调参与了包括ALS在内的几种神经退行性疾病的发病和进展。在本研究中，我们使用来自基因表达综合数据库（GEO）的公开可用数据集进行了生物信息学分析，以研究免疫细胞和基因改变在ALS中的作用。单样本基因集富集分析显示，与对照组相比，ALS患者中多种类型免疫细胞的浸润增加，包括巨噬细胞、1型/17型辅助性T细胞和活化的CD4 + /CD8 + T细胞。加权基因共表达网络分析确定了与ALS相关的免疫基因。基因本体分析显示，受体和细胞因子活性是最富集的术语。通路分析表明，这些基因不仅在免疫相关通路（如细胞因子-细胞因子受体相互作用）中富集，而且在PI3K-AKT和MAPK信号通路中也富集。基于最小绝对收缩和选择算子分析，确定了19个免疫相关基因（、、、、、、、、、、、、、、、、、和）为枢纽基因。该基因特征可以区分ALS患者和非神经学对照（<0.001），并预测疾病发生（训练集中AUC = 0.829；测试集中AUC = 0.862）。总之，我们的研究为ALS的疾病诊断和治疗监测提供了潜在的生物标志物。
