Identification of potential biomarkers and immune infiltration characteristics in severe asthma.

Identification of potential biomarkers and immune infiltration characteristics in severe asthma.
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重度哮喘潜在生物标志物和免疫浸润特征的鉴定

DOI:
10.1177/03946320221114194
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发表时间:
2022-01
影响因子:
3.5
通讯作者:
Feng J
Feng J
中科院分区:
医学4区
文献类型:
--
作者:
Jiang Y;Deng S;Hu X;Luo L;Zhang Y;Zhang D;Li X;Feng J

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目的:我们希望找到可以作为哮喘严重程度标志物的关键分子,并研究它们与严重哮喘免疫细胞浸润的相关性。方法:从Gene Expression Omnibus数据库下载哮喘数据集,用R软件进行处理,获得差异表达基因(differential Expression genes, DEGs)。首先,应用多个富集平台分析与deg相关的关键生物过程和途径以及蛋白质-蛋白质相互作用网络。接下来,我们结合最小绝对收缩和选择算子逻辑回归以及支持向量机递归特征消除算法来筛选严重哮喘的诊断标记。然后,一个由40名哮喘患者组成的本地队列(24名中度哮喘患者和16名重度哮喘患者)被用于生物标志物验证。最后用CIBERSORT评价哮喘支气管肺泡灌洗液中免疫细胞的浸润情况及其与筛选标志物的相关性。结果:本研究共鉴定出97个deg。这些基因大多富集于哮喘生物学过程中的T细胞活化和免疫应答中。cc趋化因子受体7(CCR7)和自然杀伤细胞蛋白7(NKG7)被确定为重度哮喘的标志物。合并CCR7和NKG7的新指标的ROC曲线下面积(AUC)最高(AUC = 0.851, p < 0.05)。重度哮喘组静息期和活化记忆期CD4 T细胞、活化NK细胞、CD8 T细胞明显增高(p < 0.01)。CCR7和NKG7与这些浸润细胞显著相关,两组间存在差异。CCR7与支气管肺泡灌洗液中嗜酸性粒细胞浸润呈显著正相关(r = 0.38, p < 0.05)。结论:CCR7和NKG7可能作为哮喘严重程度的潜在标志物,其表达可能与哮喘中重度组免疫细胞浸润的差异有关。
Objectives: We hope to identify key molecules that can be used as markers of asthma severity and investigate their correlation with immune cell infiltration in severe asthma. Methods: An asthma dataset was downloaded from the Gene Expression Omnibus database and then processed by R software to obtain differentially expressed genes (DEGs). First, multiple enrichment platforms were applied to analyze crucial biological processes and pathways and protein–protein interaction networks related to the DEGs. We next combined least absolute shrinkage and selection operator logistic regression and the support vector machine-recursive feature elimination algorithms to screen diagnostic markers of severe asthma. Then, a local cohort consisting of 40 asthmatic subjects (24 with moderate asthma and 16 with severe asthma) was used for biomarker validation. Finally, infiltration of immune cells in asthma bronchoalveolar lavage fluid and their correlation with the screened markers was evaluated by CIBERSORT. Results: A total of 97 DEGs were identified in this study. Most of these genes are enriched in T cell activation and immune response in the asthma biological process. CC-chemokine receptor 7 (CCR7) and natural killer cell protein 7(NKG7) were identified as markers of severe asthma. The highest area under the ROC curve (AUC) was from a new indicator combining CCR7 and NKG7 (AUC = 0.851, adj. p < 0.05). Resting and activated memory CD4 T cells, activated NK cells, and CD8 T cells were found to be significantly higher in the severe asthma group (adj. p < 0.01). CCR7 and NKG7 were significantly correlated with these infiltrated cells that showed differences between the two groups. In addition, CCR7 was found to be significantly positively correlated with eosinophils (r = 0.38, adj. p < 0.05) infiltrated in bronchoalveolar lavage fluid. Conclusion: CCR7 and NKG7 might be used as potential markers for asthma severity, and their expression may be associated with differences in immune cell infiltration in the moderate and severe asthma groups.
DOI: 10.1093/nar/gkx1313
发表时间: 2018-04-06
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单细胞转录组分析揭示哮喘急性发作患者肺部的关键免疫细胞表型
DOI: 10.1016/j.jaci.2020.09.032
发表时间: 2021-03-04
影响因子: 14.2
作者:
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DOI: 10.1007/s12016-018-8712-1
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影响因子: 9.1
作者:
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