Circulating microRNAs as biomarkers in patients with allergic rhinitis and asthma

Circulating microRNAs as biomarkers in patients with allergic rhinitis and asthma
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DOI:
10.1016/j.jaci.2016.01.029
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发表时间:
2016-05-01
影响因子:
14.2
通讯作者:
Ishmael, Faoud T.
Ishmael, Faoud T.
中科院分区:
医学1区
文献类型:
--
作者:
Panganiban, Ronaldo P.;Wang, Yanli;Ishmael, Faoud T.

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背景:微小RNA(microRNAs,miRNAs)是一种重要的调控分子,可能参与多种疾病的发病机制。循环中的miRNAs可能是诊断和表征哮喘和变应性鼻炎(AR)的非侵袭性生物标志物。目的:探讨miRNAs在哮喘患者、非哮喘AR患者和非变应性非哮喘受试者血液中的差异表达。此外,我们试图建立是否可以使用miRNAs来表征或分型哮喘patients.Methods:血浆miRNAs的表达进行了测定,采用实时定量PCR在35例哮喘患者,25例非哮喘患者AR,和19个非过敏性非哮喘受试者。通过使用Kruskal-Wallis单因素ANOVA和Bonferroni P值调整来鉴定差异表达的miRNA,以校正多重比较。一个随机森林分类算法结合留一法交叉验证的方法来评估的预测能力的轮廓miRNAs.Results:我们确定了30个健康,过敏,哮喘受试者之间的差异表达的miRNA。这些miRNAs适合于5种不同的表达模式组。在哮喘患者中,miRNA表达谱鉴定出2种亚型,其不同之处在于外周血嗜酸性粒细胞水平的高低。循环中的miR-125 b、miR-16、miR-299- 5 p、miR-126、miR-206和miR-133 b水平最能预测过敏和哮喘状态。结论:循环中的miRNA亚群在AR和哮喘患者中独特表达,并有可能用作诊断和表征这些疾病的非侵入性生物标志物。
Background: MicroRNAs (miRNAs) are emerging as important regulatory molecules that might be involved in the pathogenesis of various diseases. Circulating miRNAs might be noninvasive biomarkers to diagnose and characterize asthma and allergic rhinitis (AR).Objective: We sought to determine whether miRNAs are differentially expressed in the blood of asthmatic patients compared with those in the blood of nonasthmatic patients with AR and nonallergic nonasthmatic subjects. Furthermore, we sought to establish whether miRNAs could be used to characterize or subtype asthmatic patients.Methods: Expression of plasma miRNAs was measured by using real-time quantitative PCR in 35 asthmatic patients, 25 nonasthmatic patients with AR, and 19 nonallergic nonasthmatic subjects. Differentially expressed miRNAs were identified by using Kruskal-Wallis 1-way ANOVA with Bonferroni P value adjustment to correct for multiple comparisons. A random forest classification algorithm combined with a leave-one-out cross-validation approach was implemented to assess the predictive capacities of the profiled miRNAs.Results: We identified 30 miRNAs that were differentially expressed among healthy, allergic, and asthmatic subjects. These miRNAs fit into 5 different expression pattern groups. Among asthmatic patients, miRNA expression profiles identified 2 subtypes that differed by high or low peripheral eosinophil levels. Circulating miR-125b, miR-16, miR-299-5p, miR-126, miR-206, and miR-133b levels were most predictive of allergic and asthmatic status.Conclusions: Subsets of circulating miRNAs are uniquely expressed in patients with AR and asthmatic patients and have potential for use as noninvasive biomarkers to diagnose and characterize these diseases.