基于miRNA及临床指标的川崎病早期诊断评分体系研究  

The research of scoring system for early diagnosis of Kawasaki Disease based on miRNA and clinical indicator

作　　者：宁倩倩 陈丽琴[1] 宋思瑞 刘佳 李光 贾佳[2] 丁国徽[2] 黄敏[1] NING Qianqian;CHEN Liqin;SONG Sirui;LIU Jia;LI Guang;JIA Jia;DING Guohui;HUANG Min(Department of Cardiology,Children´s Hospital,Shanghai Jiaotong University,Shanghai 200062,China;Shanghai Center for Bioinformation Technology,Shanghai 201203,China)

机构地区：[1]上海交通大学附属儿童医院心内科,上海200062 [2]上海生物信息技术研究中心,上海201203

出　　处：《中国研究型医院》2021年第3期34-39,共6页Chinese Research Hospitals

基　　金：上海申康医院发展中心临床科技创新项目(SHDC12016119);上海市科学技术委员会科研计划项目(17411954300);上海市卫生系统先进适宜技术推广项目(2019SY025);上海市儿童医院临床培育专项(2019YLYZ01)。

摘　　要：目的探讨小儿川崎病(KD)鉴别诊断模型的分子指标,结合实验室指标为临床早期诊断提供参考。方法研究为回顾性病例分析,搜集2018年2月至11月70例确诊为KD的患儿为观察组,同期选择72例因其他原因发热时间≥3 d的患儿为对照组。两组均采用高通量测序筛查差异表达的miRNA,并对其进行实时荧光定量聚合酶链式反应(qPCR)验证。比较两组间差异表达miRNA和年龄、发热天数、红细胞沉降率(ESR)、白细胞计数(WBC)、白蛋白(ALB)、C-反应蛋白(CRP)、D-二聚体(DD)情况,通过Logistic回归分析建立数学模型并评价其效能。采用向后逐步回归分析的方法,将单因素分析中显著的因变量纳入Logistic回归分析中进行优化,保留相对重要的变量,构建早期诊断模型。结果ESR、WBC、ALB、miR-15a-5p以及miR-941通过显著性检验。通过回归方程计算患者模型得分,绘制受试者工作特征(ROC)曲线,曲线下面积(AUC)为0.975(95%CI:0.953~0.998)。选取约登指数最高得分0.417作为截断点,敏感度和特异度分别为93.5%和92.4%。结论miRNA结合常规实验室检测指标建立的KD鉴别诊断模型诊断效能较高,具有进一步大规模、多中心研究验证的临床价值。Objective To explore the molecular biomarkers of the differential diagnosis model of pediatric Kawasaki Disease(KD),combined with laboratory indicators to provide references for early clinical diagnosis.Methods This study was a retrospective case analysis.From February to November 2018,70 children diagnosed with KD were selected as the observation group,and other 72 children with fever≥3 days due to other reasons,during the same period,were selected as the control group.Both groups were processed with high-throughput sequencing to identify differentially expressed miRNAs and verified them with real-time quantitative polymerase chain reaction(qPCR).Compare the differential expression of miRNA and age,fever duration,erythrocyte sedimentation rate(ESR),white blood cell count(WBC),albumin(ALB),C-reactive protein(CRP),and D-dimer(DD)between the two groups,and use logistic regression analysis to establish a mathematical model and evaluate its effectiveness.The backward stepwise regression analysis method was used,the significant dependent variables in the univariate analysis were incorporated into the Logistic regression analysis for optimization,and the relatively important variables were retained to construct an early diagnosis model.Result ESR,WBC,ALB,miR-15a-5p,and miR-941 passed the significance testing.The regression equation calculated the patient model score,and the receiver operating characteristic curve(ROC)was drawn.The area under the curve(AUC)was 0.975(95%CI:0.953-0.998).The highest score of the Yorden index,0.417,was selected as the cutoff point,and the sensitivity and specificity were 93.5%and 92.4%,respectively.Conclusion The KD differential diagnosis model established by miRNA combined with routine laboratory test indicators has high diagnostic efficiency and has clinical value for further large-scale,multi-center research and verification.

关 键 词：黏膜皮肤淋巴结综合征 早期诊断 微RNAS 分子诊断技术 

分 类 号：R725.4[医药卫生—儿科]