Circulating MicroRNAs as Noninvasive Diagnostic Biomarkers of Liver Disease in Children With Cystic Fibrosis. Issue 2 (February 2015)

• Record Type: Journal Article
• Authors: Cook, Naomi L.; Pereira, Tamara N.; Lewindon, Peter J.; Shepherd, Ross W.; Ramm, Grant A.
• Is Part Of: Journal of pediatric gastroenterology and nutrition. Volume 60:Issue 2(2015)
• Publication Date: 2015-02
• Subjects: Children -- Nutrition -- Periodicals; Pediatric gastroenterology -- Periodicals; Infants -- Nutrition -- Periodicals; Nutrition disorders in children -- Periodicals; Child Nutrition -- Periodicals; Digestive System -- growth & development -- Periodicals; Gastrointestinal Diseases -- Periodicals; Infant Nutrition -- Periodicals; Nutrition Disorders -- Periodicals; Child; 618.923
• DOI: 10.1097/MPG.0000000000000600
• Languages: English
• ISSNs: 0277-2116

Abstract

<abstract> <title>ABSTRACT</title> <sec> <title>Objectives:</title> <p>Cystic fibrosis liver disease (CFLD), resulting from progressive hepatobiliary fibrosis, causes significant morbidity and mortality in up to 20% of children with cystic fibrosis (CF). Both pathogenesis and early detection of CFLD are elusive. Current diagnostic procedures to detect early CFLD and stage fibrosis severity are inadequate. Recent studies highlight a role for microRNAs (miRNAs) in the pathogenesis of many diseases and have suggested that serum miRNAs could be used as diagnostic biomarkers.</p> </sec> <sec> <title>Methods:</title> <p>We profiled circulating serum miRNA levels in patients with CFLD (n = 52), patients with CF without liver disease (CFnoLD, n = 30), and non-CF pediatric controls (n = 20). Extracted RNA was subjected to polymerase chain reaction (PCR) array of 84 miRNAs detectable in human serum. Seven candidate miRNAs identified were validated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), normalizing data to geNorm-determined stable reference genes, miR-19b and miR-93.</p> </sec> <sec> <title>Results:</title> <p>miR-122 was significantly elevated in patients with CFLD versus patients with CFnoLD and controls (<italic>P</italic> < 0.0001). miR-25 (<italic>P</italic> = 0.0011) and miR-21 (<italic>P</italic> = 0.0133) were elevated in patients with CFnoLD versus patients with CFLD and controls. CFLD was discriminated by both miR-122 (area under the curve [AUC] 0.71, <italic>P</italic> = 0.002) and miR-25 (AUC 0.65, <italic>P</italic> = 0.026). Logistic regression combining 3 miRNAs (-122, -25, -21) was greatly predictive of detecting CFLD (AUC 0.78, <italic>P</italic> < 0.0001). A combination of 6 miRNAs (-122, -21, -25, -210, -148a, -19a) distinguished F0 from F3–F4 fibrosis (AUC 0.73, <italic>P</italic> = 0.04), and miR-210 combined with miR-22 distinguished F0 fibrosis from any fibrosis, that is, F1–F4 (AUC 0.72, <italic>P</italic> = 0.02).</p> </sec> <sec> <title>Conclusions:</title> <p>These data provide the first evidence of changes to circulating miRNA levels in CF, suggesting that serum-based miRNA analysis may complement and extend current CFLD screening strategies with potential to predict early hepatic fibrosis.</p> </sec> </abstract>