Department of Neurology, Pusan National University School of Medicine, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea.
School of Systems Biomedical Science, Soongsil University, Seoul, Korea.
J Vestib Res. 2020;30(6):363-374. doi: 10.3233/VES-200044.
This study aimed to investigate the underlying pathogenesis of acute unilateral vestibulopathy (AUV) using gene expression profiling combined with bioinformatics analysis.
Total RNA was extracted from the peripheral blood mononuclear cells of ten AUV patients in the acute phase and from ten controls. The differentially expressed genes (DEGs) between these two groups were screened using microarray analysis with the cut-off criteria (|fold changes| > 1.5 and p-value < 0.05). Functional enrichment analysis of DEGs was performed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis, and the protein-protein interaction (PPI) network was constructed using the STRING (Search Tool for the Retrieval of Interacting Genes) database.
There were 57 DEGs (50 up-regulated and 7 down-regulated) identified in the AUV group. Functional enrichment analysis showed that most of the up-regulated DEGs were significantly enriched in terms related to the neutrophil-mediated immune pathway. From the PPI network, the top ten hub genes were extracted by calculating four topological properties, and most of them were related to the innate immune system, inflammatory processes and vascular disorders. The complete blood count tests showed that the neutrophil-to-lymphocyte ratio was significantly higher in the 72 AUV patients than in the age-matched controls (2.93±2.25 vs 1.54±0.61, p < 0.001).
This study showed that the neutrophil-mediated immune pathway may contribute to the development of AUV by mediating inflammatory and thrombotic changes in the vestibular organ.
本研究旨在通过基因表达谱分析结合生物信息学分析,探讨急性单侧前庭病(AUV)的潜在发病机制。
从 10 例急性 AUV 患者和 10 例对照者的外周血单个核细胞中提取总 RNA。采用微阵列分析筛选两组间差异表达基因(DEGs),筛选标准为|fold changes|>1.5 和 p 值<0.05。使用基因本体论和京都基因与基因组百科全书通路分析对 DEGs 进行功能富集分析,并用 STRING(Search Tool for the Retrieval of Interacting Genes)数据库构建蛋白-蛋白相互作用(PPI)网络。
在 AUV 组中发现了 57 个 DEGs(50 个上调和 7 个下调)。功能富集分析显示,大多数上调的 DEGs 显著富集于与中性粒细胞介导的免疫途径相关的术语中。从 PPI 网络中,通过计算四个拓扑属性提取了前十个枢纽基因,其中大多数与先天免疫系统、炎症过程和血管紊乱有关。全血细胞计数检查显示,72 例 AUV 患者的中性粒细胞与淋巴细胞比值明显高于年龄匹配的对照组(2.93±2.25 比 1.54±0.61,p<0.001)。
本研究表明,中性粒细胞介导的免疫途径可能通过介导前庭器官的炎症和血栓形成变化,导致 AUV 的发生。