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川崎病的血小板 microRNA 谱:新型诊断生物标志物的鉴定。

The Platelet microRNA Profile of Kawasaki Disease: Identification of Novel Diagnostic Biomarkers.

机构信息

Department of Cardiology, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai 200062, China.

Shanghai Qianbei Clinical Laboratory Co., Ltd., Shanghai 201612, China.

出版信息

Biomed Res Int. 2020 Jul 17;2020:9061568. doi: 10.1155/2020/9061568. eCollection 2020.

Abstract

Challenging diagnosis and unknown etiology of Kawasaki disease (KD) increase the coronary artery lesions incidence. microRNAs (miRNAs) are the most promising biomarkers because of their stability in peripheral blood and noninvasive measurement procedure, whose potential utility have been proved in cancers. To explore the utility of differentially expressed (DE) miRNAs as early diagnostic markers, 44 patients (25 incomplete KD and 19 complete KD) and 31 febrile controls were recruited for small RNA sequencing. From all the 1922 expressed miRNA, 210 DE miRNAs were found between KD and febrile control groups. Though platelet miRNA profiles of complete KD incomplete KD were much similar through cluster analysis, the DE miRNAs were not identical. Eight DE miRNAs were validated by real-time quantitative PCR (qRT-PCR) in complete or incomplete KD groups using a normalizer, miR-126-3p, which was identified by geNorm and NormFinder tools. The expression level of miRNAs continuous changed over time was observed and the function analysis showed the potential role of miRNAs as therapeutic biomarkers. Additionally, the prediction model for KD showed a sensitivity of 78.8% and a specificity of 71.4%, respectively. This study used small RNA sequencing to identify miRNA biomarkers KD diagnosis based on a large sample size. Our findings shine a light on the understanding of molecular pathogenesis of KD and may improve the accuracy of KD diagnosis and prognosis in clinical.

摘要

川崎病(KD)的诊断具有挑战性,病因不明,这增加了冠状动脉损伤的发生率。微小 RNA(miRNA)是最有前途的生物标志物,因为它们在外周血中稳定且具有非侵入性的测量程序,其潜在的应用已经在癌症中得到了证实。为了探索差异表达(DE)miRNA 作为早期诊断标志物的效用,招募了 44 名患者(25 名不完全 KD 和 19 名完全 KD)和 31 名发热对照组进行小 RNA 测序。在所有表达的 1922 个 miRNA 中,KD 和发热对照组之间发现了 210 个 DE miRNA。尽管通过聚类分析发现完全 KD 和不完全 KD 的血小板 miRNA 图谱非常相似,但 DE miRNA 并不相同。使用归一化因子 miR-126-3p 通过实时定量 PCR(qRT-PCR)在完全或不完全 KD 组中验证了 8 个 DE miRNA,该归一化因子是通过 geNorm 和 NormFinder 工具确定的。观察到 miRNA 表达水平随时间连续变化,功能分析表明 miRNA 作为治疗生物标志物的潜在作用。此外,KD 的预测模型的灵敏度分别为 78.8%和特异性为 71.4%。本研究使用小 RNA 测序,基于大样本量,确定了 miRNA 标志物用于 KD 诊断。我们的研究结果阐明了对 KD 分子发病机制的理解,并可能提高临床 KD 诊断和预后的准确性。

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