title: MicroRNA expression profile in exosome discriminates extremely severe infections from mild infections for hand, foot and mouth disease.
abstract: BACKGROUND
  Changes of miRNAs in exosome have been reported in different disease diagnosis and provided as potential biomarkers. In this study, we compared microRNA profile in exosomes in 5 MHFMD and 5 ESHFMD as well as in 5 healthy children.
  
  
  METHODS
  Different expression of miRNAs in exosomes across all the three groups were screened using miRNA microarray method. Further validated test was conducted through quantitative real-time PCR assays with 54 exosome samples (18 ESHFMD, 18 MHFMD, and 18 healthy control). The judgment accuracy was then estimated by the receiver operating characteristic (ROC) curve analysis; and the specificity and sensitivity were evaluated by the multiple logistic regression analysis.
  
  
  RESULTS
  There were 11 different miRNAs in exosomes of MHFMD and ESHFMD compared to healthy children, of which 4 were up-regulated and 7 were down-regulated. Further validation indicated that the 4 significant differentially expressed candidate miRNAs (miR-671-5p, miR-16-5p, miR-150-3p, and miR-4281) in exosome showed the same changes as in the microarray analysis, and the expression level of three miRNAs (miR-671-5p, miR-16-5p, and miR-150-3p) were significantly different between MHFMD or ESHFMD and the healthy controls. The accuracy of the test results were high with the under curve (AUC) value range from 0.79 to 1.00. They also provided a specificity of 72%-100% and a sensitivity of 78%-100%, which possessed ability to discriminate ESHFMD from MHFMD with the AUC value of 0.76-0.82.
  
  
  CONCLUSIONS
  This study indicated that the exosomal miRNA from patients with different condition of HFMD express unique miRNA profiles. Exosomal miRNA expression profiles may provide supplemental biomarkers for diagnosing and subtyping HFMD infections.
authors.forename: Hong-Ling
authors.initials: HL
authors.lastname: Jia
authors.forename: Chun-Hui
authors.initials: CH
authors.lastname: He
authors.forename: Zhuo-Ya
authors.initials: ZY
authors.lastname: Wang
authors.forename: Yu-Fen
authors.initials: YF
authors.lastname: Xu
authors.forename: Gen-Quan
authors.initials: GQ
authors.lastname: Yin
authors.forename: Li-Jia
authors.initials: LJ
authors.lastname: Mao
authors.affiliation: Guangzhou Women and Children's Medical Center, Guangzhou 510120, Guangdong, China. chwliu@hotmail.com.
authors.forename: Chao-Wu
authors.initials: CW
authors.lastname: Liu
authors.forename: Li
authors.initials: L
authors.lastname: Deng
mesh_terms: D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D003937:Diagnosis, Differential; D055354:Exosomes / Q000235:genetics / Q000378:metabolism*; D063990:Gene Ontology; D006232:Hand, Foot and Mouth Disease / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D058977:Molecular Sequence Annotation; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction; D012720:Severity of Illness Index; D059467:Transcriptome; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D035683:MicroRNAs