Identification of Candidate Blood mRNA Biomarkers in Intracerebral Hemorrhage Using Integrated Microarray and Weighted Gene Co-expression Network Analysis.
Identification of Candidate Blood mRNA Biomarkers in Intracerebral Hemorrhage Using Integrated Microarray and Weighted Gene Co-expression Network Analysis.
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DOI：
10.3389/fgene.2021.707713
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发表时间：
2021
影响因子：
3.7
通讯作者：
He Z
中科院分区：
文献类型：
--
作者：
Jin F;Li L;Hao Y;Tang L;Wang Y;He Z
脑出血（ICH）是一种严重的公共卫生危害，由于其高发病率，残疾和死亡率。目前，ICH的确切分子机制尚不清楚。我们尝试通过微阵列分析和加权基因共表达网络分析（WGCNA）来确定ICH相关的候选血液信使RNA（mRNA）生物标志物。我们收集了ICH患者（n = 4）和血管危险因素（VRF）对照组（n = 4）的血液样本，并通过竞争性内源性RNA（ceRNA）芯片分析了mRNA表达谱。在此基础上，构建了一个加权的基因共表达网络。具有临床意义的模块进行了区分。然后，我们下载了两个基因表达综合数据集（GEO）（GSE 24265和GSE 125512）。通过我们的微阵列中的DEG、关键模块中的感兴趣的基因和GSE 24265中的DEG的交叉来鉴定候选mRNA。利用基因本体论（GO）和京都基因和基因组百科全书（KEGG）进行功能分析，并构建蛋白质-蛋白质相互作用（PPI）网络。在我们的微阵列中，在ICH组和对照组之间总共鉴定了340个DEG。在WGCNA建立的8个基因模块中，包含191个基因的黄色模块与ICH的关联性最强。鉴定了四种候选mRNA（C3AR 1、PAWR、ARNTL2和LDLRAD 4）。在脑出血早期（24 h内），C3AR 1、PAWR和ARNTL2在血肿周围组织中呈高表达，而在外周血中呈低表达;在脑出血晚期（首次抽血后72 h），C3AR 1和PAWR在外周血中呈明显上升趋势。功能分析表明，候选基因涉及Wnt信号通路和钙信号通路等多条通路。它们可能通过神经炎症、细胞凋亡和细胞凋亡等途径影响脑出血的发生发展。我们确定了四种与ICH相关的候选血液mRNA（C3AR 1，PAWR，ARNTL2和LDLRAD 4）。它们在外周血和血肿周围组织中表现出不同的表达模式，并随时间而变化。它们可能通过神经炎症、细胞凋亡和细胞凋亡在脑出血中发挥重要作用，并可能为脑出血的新生物标志物或治疗靶点提供新的线索。
Intracerebral hemorrhage (ICH) is a serious public health hazard due to its high morbidity, disability, and mortality. Currently, the exact molecular mechanisms of ICH are unknown. We tried to identify the ICH-related candidate blood messenger RNA (mRNA) biomarkers by microarray analysis and weighted gene co-expression network analysis (WGCNA). We collected the blood samples from patients with ICH (n = 4) and from vascular risk factor (VRF) controls (n = 4) and analyzed the mRNA expression profiles by competitive endogenous RNA (ceRNA) microarray. Differentially expressed genes (DEGs) were identified and then a weighted gene co-expression network was constructed. Modules with clinical significance were distinguished. Then, we downloaded two Gene Expression Omnibus (GEO) datasets (GSE24265 and GSE125512). Candidate mRNAs were identified by taking the intersection of the DEGs in our microarray, the interesting genes in the key module, and the DEGs in GSE24265. Functional analysis involving Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) and construction of a protein–protein interaction (PPI) network were conducted. A total of 340 DEGs in our microarray were identified between the ICH group and the control group. Among the eight gene modules established by WGCNA, the yellow module containing 191 genes was the most strongly associated with ICH. Four candidate mRNAs (C3AR1, PAWR, ARNTL2, and LDLRAD4) were identified. In the early stage of ICH (within 24 h), C3AR1, PAWR, and ARNTL2 were highly expressed in the perihematomal tissue, but with low expressions in peripheral blood; in the late stage (72 h after the first blood draw), an obvious upward trend of C3AR1 and PAWR in peripheral blood was seen. Functional analysis showed that candidate mRNAs were concerned with multiple pathways, such as the Wnt signaling pathway and calcium signaling pathway. They might affect the process of ICH through neuroinflammation, cell apoptosis, and pyroptosis. We identified four candidate blood mRNAs (C3AR1, PAWR, ARNTL2, and LDLRAD4) related to ICH. They showed different expression patterns in peripheral blood and perihematomal tissues and changed with time. They might play important roles in ICH through neuroinflammation, cell apoptosis, and pyroptosis and might shed new light to novel biomarkers or therapeutic targets in ICH.
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影响因子：
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Stamova, Boryana