PDF(Pubmed)
Abstract：
Ischemic stroke is the leading cause of long-term disability in adults, accounting for 80% of stroke cases. Diffusion weighted imaging (DWI) examination is the main test for acute ischemic stroke, but in recent years, several studies have shown that some patients show negative DWI examination after the onset of ischemic stroke with symptoms of significant neurological deficits. In this study, we investigated potential biomarkers related to immune metabolism in the peripheral blood of DWI-negative versus DWI-positive patients after ischemic stroke and explored their possible regulatory processes in ischemic stroke. The datasets related to ischemic stroke were downloaded from the GEO database, immune-related genes and metabolism-related genes were obtained from the ImmPort database and MSigDB database, respectively, and immune-related differential genes were obtained based on immune scores using the algorithm of the R software package \"GSVA.\" Candidate genes were selected based on intersections, hub genes were screened using the algorithm in Cytoscape software, and finally, GeneMANIA analysis, GSEA enrichment analysis, subcellular localization, gene transcription factor and gene-drug interaction networks, and disease correlation analyses were performed for the hub genes. Five hub genes (GART, TYMS, PPAT, CTPS1, and PAICS) were obtained by PPI network analysis and software analysis. Among them, PPAT and PAICS may be the real hub genes with consistent and significantly differentiated results from the discovery and validation sets. The functions of these hub genes may be related to pathways such as nucleotide biosynthetic processes. The constructed hub gene ceRNA network showed that hsa-10a-5p is the key miRNA connecting PAICS and multiple lncRNAs in this study. Differential genes related to immunity and metabolism in DWI-negative and DWI-positive patients after IS were identified using bioinformatics analysis, and their pathways and related TF-RNAs, miRNAs, and lncRNAs were identified. These genes may be considered effective targets for the diagnosis and treatment of ischemic stroke.
摘要：
缺血性中风是成年人长期残疾的主要原因，占中风病例的80%。弥散加权成像(DWI)检查是急性缺血性脑卒中的主要检查方法,但近年来,多项研究表明,一些患者在缺血性卒中发病后DWI检查阴性,出现明显的神经功能缺损症状.在这项研究中,我们研究了缺血性卒中后DWI阴性和DWI阳性患者外周血中与免疫代谢相关的潜在生物标志物,并探讨了其在缺血性卒中中可能的调节过程.从GEO数据库下载与缺血性卒中相关的数据集，免疫相关基因和代谢相关基因从ImmPort数据库和MSigDB数据库获得,分别,和免疫相关的差异基因是使用R软件包\"GSVA的算法基于免疫评分获得的。“候选基因是根据交叉点选择的，使用Cytoscape软件中的算法筛选集线器基因，最后，遗传MANIA分析,GSEA富集分析,亚细胞定位，基因转录因子和基因-药物相互作用网络，并对hub基因进行了疾病相关性分析。五个中心基因(GART，TYMS,PPAT,通过PPI网络分析和软件分析获得CTPS1和PAICS）。其中,PPAT和PAICS可能是真正的枢纽基因，具有来自发现和验证集的一致且显着区分的结果。这些hub基因的功能可能与诸如核苷酸生物合成过程的途径有关。构建的hub基因ceRNA网络显示，hsa-10a-5p是本研究中连接PAICS和多个lncRNA的关键miRNA。使用生物信息学分析鉴定DWI阴性和DWI阳性患者IS后与免疫和代谢相关的差异基因。以及它们的通路和相关的TF-RNA，miRNA,并鉴定了lncRNAs。这些基因可能被认为是诊断和治疗缺血性中风的有效靶标。
