title: Serum microRNA expression profile distinguishes enterovirus 71 and coxsackievirus 16 infections in patients with hand-foot-and-mouth disease.
abstract: Altered circulating microRNA (miRNA) profiles have been noted in patients with microbial infections. We compared host serum miRNA levels in patients with hand-foot-and-mouth disease (HFMD) caused by enterovirus 71 (EV71) and coxsackievirus 16 (CVA16) as well as in other microbial infections and in healthy individuals. Among 664 different miRNAs analyzed using a miRNA array, 102 were up-regulated and 26 were down-regulated in sera of patients with enteroviral infections. Expression levels of ten candidate miRNAs were further evaluated by quantitative real-time PCR assays. A receiver operating characteristic (ROC) curve analysis revealed that six miRNAs (miR-148a, miR-143, miR-324-3p, miR-628-3p, miR-140-5p, and miR-362-3p) were able to discriminate patients with enterovirus infections from healthy controls with area under curve (AUC) values ranged from 0.828 to 0.934. The combined six miRNA using multiple logistic regression analysis provided not only a sensitivity of 97.1% and a specificity of 92.7% but also a unique profile that differentiated enterovirial infections from other microbial infections. Expression levels of five miRNAs (miR-148a, miR-143, miR-324-3p, miR-545, and miR-140-5p) were significantly increased in patients with CVA16 versus those with EV71 (p<0.05). Combination of miR-545, miR-324-3p, and miR-143 possessed a moderate ability to discrimination between CVA16 and EV71 with an AUC value of 0.761. These data indicate that sera from patients with different subtypes of enteroviral infection express unique miRNA profiles. Serum miRNA expression profiles may provide supplemental biomarkers for diagnosing and subtyping enteroviral HFMD infections.
authors.affiliation: Institute of Pathogen Microbiology, Jiangsu Provincial Center for Disease Prevention and Control, Nanjing, China.
authors.forename: Lunbiao
authors.initials: L
authors.lastname: Cui
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Qi
authors.forename: Haijing
authors.initials: H
authors.lastname: Li
authors.forename: Yiyue
authors.initials: Y
authors.lastname: Ge
authors.forename: Kangchen
authors.initials: K
authors.lastname: Zhao
authors.forename: Xian
authors.initials: X
authors.lastname: Qi
authors.forename: Xiling
authors.initials: X
authors.lastname: Guo
authors.forename: Zhiyang
authors.initials: Z
authors.lastname: Shi
authors.forename: Minghao
authors.initials: M
authors.lastname: Zhou
authors.forename: Baoli
authors.initials: B
authors.lastname: Zhu
authors.forename: Yan
authors.initials: Y
authors.lastname: Guo
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Charles W
authors.initials: CW
authors.lastname: Stratton
authors.forename: Yi-Wei
authors.initials: YW
authors.lastname: Tang
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
mesh_terms: D003384:Coxsackievirus Infections / Q000175:diagnosis*; D003937:Diagnosis, Differential; D029821:Enterovirus A, Human; D004769:Enterovirus Infections / Q000175:diagnosis*; D005786:Gene Expression Regulation; D006232:Hand, Foot and Mouth Disease / Q000175:diagnosis / Q000235:genetics / Q000382:microbiology*; D006801:Humans; D035683:MicroRNAs / Q000097:blood*; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D012372:ROC Curve; D012680:Sensitivity and Specificity
chemical_list: D035683:MicroRNAs
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