Cui Shasha, Zhao Yunfeng, Huang Menghui, Zhang Huan, Zhao Wei, Chen Zhenhua
Nantong Health College of Jiangsu Province, East Zhenxing Road 288#, Nantong 226010, China.
Department of Critical Care Medicine, Affiliated Hospital 2 of Nantong University and First People's Hospital of Nantong City, North Haierxiang Road 6#, Nantong 226001, China.
Evid Based Complement Alternat Med. 2022 Sep 1;2022:7634509. doi: 10.1155/2022/7634509. eCollection 2022.
Several blood biomarkers are now considered increasingly important for stratifying risk, monitoring disease progression, and evaluating the response to therapy in ischemic stroke. The purpose of the present study was to identify the key genes associated with ischemic stroke progression and elucidate the potential therapeutic small molecules. Microarray datasets related to stroke for GSE58294, GSE22255, and GSE16561 were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were filtered using the Limma package. DAVID was then searched to perform gene ontology (GO) and pathway enrichment analyses. Based on the DEGs, a protein-protein interaction (PPI) network was developed using Cytoscape, and MCODE was applied to conduct module analysis. Finally, to identify the potential drugs for ischemic stroke, the connectivity map (CMap) database was used. Sixty DEGs were identified after analyzing the three datasets. The GO data analysis revealed that the DEGs were significantly associated with biological processes, including positive regulation of programmed cell death, protein localization in organelles, and positive regulation of apoptosis. KEGG analysis showed that the DEGs were particularly enriched in the Fc epsilon RI signaling pathway, MAPK signaling pathway, and Huntington's disease. We selected five DEGs with high connectivity (CYBB, SYK, DUSP1, TNF, and SP1) that significantly predicted stroke progression. In addition, CMap prediction showed ten small molecules that could be used as adjuvants when treating ischemic stroke. The outcomes of the present study indicated that the five genes mentioned above can be considered potential targets for developing new medications that can modify the ischemic stroke process, and mycophenolic acid was the most promising small molecule to treat ischemic stroke.
目前，几种血液生物标志物在缺血性中风的风险分层、疾病进展监测以及治疗反应评估中被认为越来越重要。本研究的目的是识别与缺血性中风进展相关的关键基因，并阐明潜在的治疗性小分子。从基因表达综合数据库（GEO）中获取了与中风相关的GSE58294、GSE22255和GSE16561芯片数据集。使用Limma软件包筛选差异表达基因（DEG）。然后利用DAVID进行基因本体（GO）和通路富集分析。基于这些DEG，使用Cytoscape构建蛋白质-蛋白质相互作用（PPI）网络，并应用MCODE进行模块分析。最后，为了识别缺血性中风的潜在药物，使用了连接图谱（CMap）数据库。分析这三个数据集后，共识别出60个DEG。GO数据分析表明，这些DEG与生物学过程显著相关，包括程序性细胞死亡的正调控、蛋白质在细胞器中的定位以及细胞凋亡的正调控。KEGG分析表明，这些DEG在FcεRI信号通路、MAPK信号通路和亨廷顿病中尤其富集。我们选择了五个具有高连接性的DEG（CYBB、SYK、DUSP1、TNF和SP1），它们能显著预测中风进展。此外，CMap预测显示有十种小分子可在治疗缺血性中风时用作佐剂。本研究结果表明，上述五个基因可被视为开发能够改变缺血性中风进程的新药物的潜在靶点，而霉酚酸是治疗缺血性中风最有前景的小分子。
