儿童手足口病患者EV-71和Cox-A16感染与血清miRNA谱特征的相关性研究OA
Study on the Correlation of EV-71 and Cox-A16 Infections with Serum miRNA Profiles in Pediatric Hand-Foot-and-Mouth Disease
目的 分析儿童手足口病(HFMD)患者肠道病毒71型(EV-71)或柯萨奇病毒A组16型(Cox-A16)感染的血清微小核糖核酸(miRNA)谱,并探讨其临床意义.方法 采用简单随机抽样法,选取2023年11月～2024年8月在重庆医科大学附属大足医院儿科确诊的儿童HFMD患者.发现集包含EV-71或Cox-A16单一感染患儿各8例,采用miRNA微阵列筛选差异表达miRNA,并进行生物信息学分析;验证集包含Cox-A16组、EV-71组以及健康对照组各105例,采用实时荧光定量聚合酶链反应法检测血清miRNA水平.使用受试者操作特征(ROC)曲线开发基于miRNA的诊断模型.结果 通过发现集筛选,识别5个差异表达miRNA(miR-21、miR-143、miR-494、miR-146a、miR-221),基因本体论和京都基因和基因组百科全书通路富集证实了这些差异表达miRNA与多种免疫相关通路有关.在验证集中,EV-71组和Cox-A16组患儿血清miR-21、miR-143、miR-494、miR-146a、miR-221水平均显著高于健康对照组,差异具有统计学意义(H=7.714～100.551,均P<0.05),且EV-71组血清miR-21、miR-494、miR-143、miR-146a水平高于Cox-A16组(Z=-37.215～-9.443,均P<0.05).调整年龄等临床变量后,miR-21、miR-494、miR-143、miR-221、miR-146a水平升高仍然与HFMD发病显著相关(HR=1.104～1.400,均P<0.05).5种miRNA具有诊断HFMD的能力,ROC曲线下面积(AUC)为0.584～0.874.miR-21、miR-494、miR-146a的组合具有区分诊断EV-71或Cox-A16单一病毒亚型感染的能力,AUC为0.874.结论 儿童HFMD患者存在特异性血清miRNA谱,其中3种miRNA组合模型具有区分EV-71或Cox-A16单一亚型感染的能力.
Objective To characterize the serum microRNA(miRNA)profile in pediatric hand-foot-and-mouth disease(HFMD)caused by Enterovirus 71(EV-71)or Coxsackievirus group A type 16(Cox-A16),and to analyze its clinical significance.Meth-ods Using a simple random sampling method,pediatric HFMD patients diagnosed at the Department of Pediatrics of Dazu Hos-pital Affiliated to Chongqing Medical University from November 2023 to August 2024 were enrolled.The discovery set included 8 children with EV-71 infection,and 8 with Cox-A16 infection.miRNA microarray was performed to screen for differentially expressed miRNAs.And the candidate miRNAs were analyzed by bioinformatics analysis.The validation set included Cox-A16 group,EV-71 group and healthy control group with 105 cases in each group.Serum miRNA levels were detected using real-time fluorescence quantitative polymerase chain reaction.Receiver operating characteristic(ROC)curves were used to develop a miR-NA-based diagnostic model.Results In the discovery set,five differentially expressed miRNAs(miR-21,miR-143,miR-494,miR-146a,and miR-221)were identified.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment anal-ysis confirmed that these differentially expressed miRNAs were involved in multiple immune-related pathways.In the validation set,serum levels of miR-21,miR-143,miR-494,miR-146a,and miR-221 were significantly higher in both EV-71 and Cox-A16 groups than in healthy controls(H=7.714～100.551,all P<0.05),and serum levels of miR-21,miR-494,miR-143,and miR-146a were significantly higher in the EV-71 group than the Cox-A16 group(Z=-37.215 to-9.443,all P<0.05).After adjusting for clinical variables including age,elevated levels of miR-21,miR-494,miR-143,miR-221,and miR-1466 remained significant-ly associated with the onset of HFMD(HR=1.104～1.400,all P<0.05).The five-miRNA panel showed diagnostic capability for HFMD with an area under ROC curve(AUC)values ranging from 0.584 to 0.874.Moreover,the combination of miR-21,miR-494,and miR-146a demonstrated the ability to differentiate between EV-71 and Cox-A16 single-virus subtype infections,with AUC 0.874.Conclusions Pediatric HFMD has a specific serum miRNA profile,and the three-miRNA panel(miR-21,miR-494,and miR-146a)shows potential for distinguishing EV-71 from Cox-A16 infections.
周延;雷芳;杨阳;陈岑;王廷婷
重庆医科大学附属大足医院儿科,重庆 402360重庆医科大学附属大足医院儿科,重庆 402360重庆医科大学附属大足医院儿科,重庆 402360重庆医科大学附属大足医院儿科,重庆 402360重庆医科大学附属大足医院儿科,重庆 402360
医药卫生
手足口病肠道病毒71型柯萨奇病毒A组16型儿童患者微小核糖核酸
hand-foot-mouth diseaseenterovirus 71Coxsackievirus group A type 16pediatric patientsmicroRNA
《现代检验医学杂志》 2026 (5)
20-25,6
重庆市科技发展项目(DZKJ2022JSYJ-KWXM1031).
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