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川崎病患儿外周血miRNA谱的鉴定及miR-355和miR-2911表达的临床意义

Identification of miRNA profile in the peripheral blood and clinical significance of miR-355 and miR-2911 expression in children with Kawasaki disease.

作者信息

Li Xia, Sun Ying, Cai Yanyan, Zhang Xia, Zhang Xiaojing

机构信息

Department of Pediatrics, Jinan Maternity and Child Care Hospital Affiliated to Shandong First Medical University Jinan, Shandong, China.

出版信息

Am J Transl Res. 2022 Nov 15;14(11):7820-7830. eCollection 2022.

Abstract

OBJECTIVE

To identify the abnormal expression profile of miRNA in peripheral blood of children with Kawasaki disease (KD) and explore its diagnostic value for Kawasaki disease.

METHODS

From January 2020 to June 2021, 62 children with KD (KD group) and 158 children with febrile disease (Con group) were selected as subjects. Peripheral blood was collected before treatment, and differentially expressed miRNAs in peripheral blood were identified by next generation sequencing, and the identified targets were verified by RT-PCR. The diagnostic value of miRNAs in KD was analyzed by ROC curves and linear SVM model.

RESULTS

Compared to Con group, a total of 163 differentially expressed miRNAs were detected in peripheral blood of children in the KD group, including 126 up-regulated miRNAs and 37 down-regulated miRNAs. Hierarchical clustering showed that miRNA profiles of children in the KD group and Con group were significantly different, among which 3 miRNAs wereup-regulated and 3 miRNAs were down-regulated (P<0.05). The results of miRanda and TargetScanS software showed that a total of 17159 target genes were predicted. GO function and KEGG signal pathway enrichment analysis showed that target genes were involved in a wide range of biological functions; ROC curve results showed that the sensitivity of miR-355 and miR-2911 in diagnosing KD were 73.8% and 71.2%, the specificity was 72.4% and 73.9%, and the AUC was 0.793 and 0.757, respectively. The AUC for combined detection of miR-355 and miR-2911 was increased to 0.806. A linear SVM model further verified the diagnostic value of joint detection of miR-355 and miR-2911.

CONCLUSION

Expression levels of miR-355 and miR-2911 were significantly up-regulated in peripheral blood of children with Kawasaki disease. miR-355 and miR-2911 could serve as biomarkers for diagnosis of Kawasaki disease.

摘要

目的

鉴定川崎病(KD)患儿外周血中miRNA的异常表达谱,并探讨其对川崎病的诊断价值。

方法

选取2020年1月至2021年6月期间62例KD患儿(KD组)和158例发热性疾病患儿(对照组)作为研究对象。治疗前采集外周血,通过下一代测序鉴定外周血中差异表达的miRNA,并通过RT-PCR验证鉴定出的靶点。采用ROC曲线和线性支持向量机模型分析miRNA对KD的诊断价值。

结果

与对照组相比,KD组患儿外周血中共检测到163个差异表达的miRNA,其中126个miRNA上调,37个miRNA下调。层次聚类显示,KD组和对照组患儿的miRNA谱存在显著差异,其中3个miRNA上调,3个miRNA下调(P<0.05)。miRanda和TargetScanS软件结果显示,共预测到17159个靶基因。GO功能和KEGG信号通路富集分析表明,靶基因参与广泛的生物学功能;ROC曲线结果显示,miR-355和miR-2911诊断KD的敏感性分别为73.8%和7l.2%,特异性分别为72.4%和73.9%,AUC分别为0.793和0.757。miR-355和miR-2911联合检测的AUC提高到0.806。线性支持向量机模型进一步验证了miR-355和miR-2911联合检测的诊断价值。

结论

川崎病患儿外周血中miR-355和miR-2911表达水平显著上调。miR-355和miR-2911可作为川崎病诊断的生物标志物。

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