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不同严重程度哮喘患者血清外泌体中微RNA-21的表达水平及其诊断价值
王湘云1△,陈乾2△,孙亚红3,白冲1,商艳1,3*
0
(1. 海军军医大学(第二军医大学)长海医院呼吸及危重症医学科, 上海 200433;
2. 海军军医大学(第二军医大学)基础医学院组织胚胎学教研室, 上海 200433;
3. 浙江省海宁市人民医院呼吸科, 海宁 314400
共同第一作者
*通信作者)
摘要:
目的 研究血清外泌体中微RNA-21(miR-21)表达水平及其对哮喘严重程度的诊断效能。方法 以82例未经治疗的哮喘患者和80名健康人作为研究对象。将哮喘患者根据病情严重程度分为4组:间歇状态20例、轻度持续22例、中度持续22例、重度持续18例。用qPCR检测各组血清外泌体中miR-21的表达水平,并进行比较。用Spearman相关分析研究血清外泌体中miR-21表达水平与哮喘严重程度的相关性。通过受试者工作特征(ROC)曲线评价外泌体中miR-21表达水平对哮喘严重程度的诊断效能。结果 间歇状态、轻度持续、中度持续和重度持续的哮喘患者血清外泌体中miR-21表达水平均高于健康对照组,差异均有统计学意义(P均<0.01),且哮喘患者各组间miR-21表达水平差异也有统计学意义(P均<0.01)。Spearman相关分析结果显示,血清外泌体中miR-21的相对表达量与哮喘严重程度呈正相关(r=0.974,P=0.016 7)。血清外泌体中miR-21对间歇状态、轻度持续、中度持续、重度持续哮喘患者诊断效能的ROC曲线下面积分别为0.657、0.769、0.847、0.916(P均<0.01)。结论 血清外泌体中miR-21表达水平对治疗前哮喘严重程度有较高的诊断效能,有望成为判断哮喘严重程度的一种无创性诊断标志物。
关键词:  外泌体  哮喘  微RNA-21  诊断标志物  血清
DOI:10.16781/j.0258-879x.2018.07.0740
投稿时间:2018-06-06修订日期:2018-07-18
基金项目:国家自然科学基金(81570020),浦东新区科技发展基金(PKJ2016-Y49),浙江省公益技术应用研究计划项目(2016C33216),教育部留学回国人员科研启动基金.
Expression of microRNA-21 in serum exosomes of patients with different severities of asthma and its diagnostic value
WANG Xiang-yun1△,CHEN Qian2△,SUN Ya-hong3,BAI Chong1,SHANG Yan1,3*
(1. Department of Respiratory and Critical Care Medicine, Changhai Hospital, Navy Medical University(Second Military Medical University), Shanghai 200433, China;
2. Department of Histology and Embryology, College of Basic Medical Sciences, Navy Medical University(Second Military Medical University), Shanghai 200433, China;
3. Department of Respiratory Medicine, People's Hospital of Haining, Haining 314400, Zhejiang, China
Co-first authors.
* Corresponding author)
Abstract:
Objective To determine the expression level of microRNA-21 (miR-21) in serum exosomes of patients with different severities of asthma, and to explore the diagnostic value. Methods A total of 82 patients with asthma who did not received any treatment and 80 healthy control volunteers were enrolled in this study. The asthma cases were divided into four groups according to the severity of asthma, including intermittent group (n=20), mild sustained group (n=22), moderate sustained group (n=22), and severe sustained group (n=18). Expression levels of miR-21 were determined using qPCR and the differences were compared among the five groups. Spearman correlation analysis was used to analyze the correlation between miR-21 expression level and severity of asthma. The receiver operating characteristic (ROC) curve was used to evaluate the diagnosis performance of miR-21 expression level in serum exosomes for different severities of asthma. Results The expression levels of miR-21 were significantly higher in the intermittent, mild sustained, moderate sustained and severe sustained groups than that in the healthy control group (all P<0.01). The difference of miR-21 expression level was statistically significant between the intermittent, mild sustained, moderate sustained and severe sustained groups (all P<0.01). Spearman correlation analysis showed that the relative expression level of miR-21 in serum exosomes was positively correlated with the severity of asthma (r=0.974, P=0.016 7). The areas under ROC curve of exosome miR-21 for diagnosing intermittent, mild sustained, moderate sustained and severe sustained asthma were 0.657, 0.769, 0.847 and 0.916, respectively (all P<0.01). Conclusion The expression level of miR-21 in serum exosomes is effective in diagnosing different severities of asthma, and miR-21 in serum exosomes may be a new non-invasive biomarkers.
Key words:  exosomes  asthma  microRNA-21  diagnostic biomarker  serum