Sets of serum exosomal microRNAs as candidate diagnostic biomarkers for Kawasaki disease.
Sets of serum exosomal microRNAs as candidate diagnostic biomarkers for Kawasaki disease.
复制标题
血清外泌体 microRNA 组作为川崎病候选诊断生物标志物
DOI：
10.1038/srep44706
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发表时间：
2017-03-20
影响因子：
4.6
通讯作者：
Zhang G
中科院分区：
文献类型：
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作者：
Jia HL;Liu CW;Zhang L;Xu WJ;Gao XJ;Bai J;Xu YF;Xu MG;Zhang G
虽然川崎病是儿童获得性心脏病的主要原因，但目前还没有可用的诊断生物标记物。我们的目标是利用血清外体microRNAs(MiRNAs)寻找诊断川崎病的候选生物标志物。使用来自生物库的冷冻血清样本、高通量微阵列技术、两阶段实时定量PCR和数据归一化的自参考策略，我们将候选生物标记物的列表缩小到4个miRNAs。我们进一步验证了鉴定的miRNAs(即CT(miR-1246)-CT(miR-4436b-5p)和CT(miR-197-3p)-CT(miR-671-5p))在两家医院的79份样本中的诊断能力。我们发现，这个4-miRNA集可以一次性将KD患者与其他发热患者以及健康人区分开来，假阳性和假阴性率最低。因此，我们首次提出，血清外体miRNAs可作为川崎病的候选诊断生物标记物。此外，我们描述了一种有效的策略来筛选复杂疾病的生物标记物，即使在几乎没有机械知识的情况下也是如此。
Although Kawasaki disease is the main cause of acquired heart disease in children, no diagnostic biomarkers are available. We aimed to identify candidate biomarkers for diagnosing Kawasaki disease using serum exosomal microRNAs (miRNAs). Using frozen serum samples from a biobank, high-throughput microarray technologies, two-stage real-time quantitative PCR, and a self-referencing strategy for data normalization, we narrowed down the list of biomarker candidates to a set of 4 miRNAs. We further validated the diagnostic capabilities of the identified miRNAs (namely, CT(miR-1246)-CT(miR-4436b-5p) and CT(miR-197-3p)-CT(miR-671-5p)) in 79 samples from two hospitals. We found that this 4-miRNA set could distinguish KD patients from other febrile patients as well as from healthy individuals in a single pass, with a minimal rate of false positives and negatives. We thus propose, for the first time, that serum exosomal miRNAs represent candidate diagnostic biomarkers for Kawasaki disease. Additionally, we describe an effective strategy of screening for biomarkers of complex diseases even when little mechanistic knowledge is available.