Identification of an Alveolar Macrophage-Related Core Gene Set in Acute Respiratory Distress Syndrome.

Identification of an Alveolar Macrophage-Related Core Gene Set in Acute Respiratory Distress Syndrome.
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鉴定急性呼吸窘迫综合征中肺泡巨噬细胞相关的核心基因。

DOI:
10.2147/jir.s306136
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发表时间:
2021
影响因子:
4.5
通讯作者:
Zhang J
Zhang J
中科院分区:
医学3区
文献类型:
--
作者:
Zhao C;Mo J;Zheng X;Wu Z;Li Q;Feng J;Luo J;Lu J;Zhang J

文献摘要

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急性呼吸窘迫综合征(ARDS)是一种快速进展的弥漫性肺损伤,其特点是高死亡率和急性发作。ARDS的病理机制尚不清楚。但肺泡巨噬细胞已被证明在ARDS期间的炎症反应中起重要作用。我们旨在寻找ARDS的生物标志物,为ARDS患者提供早期诊断和及时治疗。从Gene expression Omnibus (GEO)下载基因表达谱,筛选差异表达基因(DEGs)。所有数据集中常见的上调基因被定义为循环ARDS肺泡巨噬细胞相关基因(cARDSAMGs)。我们进行了功能富集分析,以探索cARDSAMGs的潜在生物学功能,并构建了蛋白-蛋白相互作用网络。采用基因集变异分析(GSVA)计算个体样本的核心基因集变异分析(CGSVA)得分。采用受试者工作特征(ROC)曲线分析CGSVA评分,评价其对ARDS的诊断能力。在所有ARDS数据集中,共有60个基因被上调,因此被命名为cardsamg。cardsamg显著参与多种炎症、免疫和吞噬相关的生物学过程和途径。在宿主ADRS应答相关的蛋白-蛋白相互作用网络中,鉴定出8个基因为核心基因集:PTCRA、JAG1、C1QB、ADAM17、C1QA、MMP9、VSIG4和TNFAIP3。ROC曲线分析显示,无论是肺泡灌洗液还是全血,CGSVA评分均可作为ARDS的生物标志物:ARDS患者的CGSVA评分均显著高于健康人。ARDS肺泡巨噬细胞相关的CGSVA评分可作为ARDS的生物标志物。
Acute respiratory distress syndrome (ARDS) is a rapidly progressive diffuse lung injury that is characterized by high mortality and acute onset. The pathological mechanisms of ARDS are still unclear. But alveolar macrophages have been shown to play an important role in inflammatory responses during ARDS. We aimed to find the biomarkers for ARDS for early diagnosis, to give ARDS patients timely treatment. Gene expression profiles were downloaded from Gene Expression Omnibus (GEO) and screened for differentially expressed genes (DEGs). The common upregulated genes in all the datasets were defined as circulating ARDS alveolar macrophage-related genes (cARDSAMGs). We performed a functional enrichment analysis to explore potential biological functions of cARDSAMGs, and we built protein–protein interaction networks. Gene set variation analysis (GSVA) was used to calculate the core gene set variation analysis (CGSVA) score for individual samples. Receiver operating characteristic (ROC) curve analysis was applied on the CGSVA score to evaluate its ability for diagnosis of ARDS. A total of 60 genes were upregulated in all ARDS datasets and were therefore denominated as cARDSAMGs. The cARDSAMGs were significantly involved in multiple inflammation-, immunity- and phagocytosis-related biological processes and pathways. In the protein–protein interaction network associated with host responses to ADRS, eight genes were identified as a core gene set: PTCRA, JAG1, C1QB, ADAM17, C1QA, MMP9, VSIG4 and TNFAIP3. ROC curve analysis showed that the CGSVA score may be considered as a biomarker for ARDS: it was significantly higher in patients with ARDS than those in healthy in both alveolar lavage fluid and whole blood. The ARDS alveolar macrophage-related CGSVA score may be useful as a biomarker for ARDS.