title: Specific serum microRNA profile in the molecular diagnosis of Hirschsprung's disease.
abstract: Hirschsprung's disease (HSCR), a congenital gastrointestinal disorder, is one of the most common causes of neonatal bowel obstruction. Without an early screening and diagnosis, some patients develop serious complications, such as toxic megacolon or acute enterocolitis. We sought to identify specific serum microRNAs (miRNAs) that can serve as novel early, non-invasive screening signature and then to test their specificity and sensitivity in diagnosing Hirschsprung's disease. We obtained serum samples from 95 HSCR cases and 104 matched controls. An initial screening of miRNA expression was performed through TaqMan Low Density Array. The candidate miRNAs were validated by individual reverse transcription quantitative real-time PCR arranged in the training and a two-stage validation set. Additional double-blind testing was performed in 23 patients with clinically suspected HSCR to evaluate the diagnostic value and accuracy of the serum miRNA profile in predicting HSCR. Following a multi-stage evaluation approach, five miRNAs were significantly increased in HSCR cases compared with controls. The areas under the receiver operating characteristic (ROC) curve of this five-serum miRNA signature were 0.895, 0.893 and 0.925 in training set and two validation sets, respectively. The accuracy rate of the five-miRNA profile as HSCR signature was 82.6%, which, in the double-blind testing set, was markedly higher than that of contrast enema (70%), the most commonly used test performed to diagnose HSCR. Our results indicate that a five-serum miRNA signature may be linked to HSCR, representing a potential, novel, non-invasive diagnostic approach for early screening of HSCR.
authors: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China; Department of Pediatric Surgery, Nanjing Children's Hospital Affiliated Nanjing Medical University, Nanjing, China.
authors: Weibing
authors: W
authors: Tang
authors: Hongxing
authors: H
authors: Li
authors: Junwei
authors: J
authors: Tang
authors: Wei
authors: W
authors: Wu
authors: Jingjing
authors: J
authors: Qin
authors: Hao
authors: H
authors: Lei
authors: Peng
authors: P
authors: Cai
authors: Weiwei
authors: W
authors: Huo
authors: Bo
authors: B
authors: Li
authors: Virender
authors: V
authors: Rehan
authors: Xiaoqun
authors: X
authors: Xu
authors: Qiming
authors: Q
authors: Geng
authors: Hongwei
authors: H
authors: Zhang
authors: Yankai
authors: Y
authors: Xia
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics*; D016022:Case-Control Studies; D004311:Double-Blind Method; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006627:Hirschsprung Disease / Q000097:blood* / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; D012333:RNA, Messenger
keywords: HSCR; diagnosis; serum miRNA; signature