Circulating microRNAs as noninvasive diagnostic biomarkers of liver disease in children with cystic fibrosis

Simple item page
dc.contributor.authorCook, N.L.
dc.contributor.authorPereira, T.N.
dc.contributor.authorLewindon, P.J.
dc.contributor.authorShepherd, R.W.
dc.contributor.authorRamm, G.A.
dc.date.issued2015
dc.description.abstractObjectives: 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. Methods: 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. Results: miR-122 was significantly elevated in patients with CFLD versus patients with CFnoLD and controls (P < 0.0001). miR-25 (P = 0.0011) and miR-21 (P = 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, P = 0.002) and miR-25 (AUC 0.65, P = 0.026). Logistic regression combining 3 miRNAs (-122, -25, -21) was greatly predictive of detecting CFLD (AUC 0.78, P < 0.0001). A combination of 6 miRNAs (-122, -21, -25, -210, -148a, -19a) distinguished F0 from F3–F4 fibrosis (AUC 0.73, P = 0.04), and miR-210 combined with miR-22 distinguished F0 fibrosis from any fibrosis, that is, F1–F4 (AUC 0.72, P = 0.02). Conclusions: 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.
dc.description.statementofresponsibilityNaomi L. Cook, Tamara N. Pereira, Peter J. Lewindon, Ross W. Shepherd, and Grant A. Ramm
dc.identifier.citationJournal of Pediatric Gastroenterology and Nutrition, 2015; 60(2):247-254
dc.identifier.doi10.1097/MPG.0000000000000600
dc.identifier.issn0277-2116
dc.identifier.issn1536-4801
dc.identifier.orcidCook, N.L. [0000-0002-1830-2432]
dc.identifier.urihttp://hdl.handle.net/2440/117945
dc.language.isoen
dc.publisherLippincott, Williams & Wilkins
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1048740
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1061332
dc.rights© 2015 by ESPGHAN and NASPGHAN
dc.source.urihttps://doi.org/10.1097/mpg.0000000000000600
dc.subjectCystic fibrosis liver disease; hepatic fibrosis; pediatrics; reference genes; RT-qPCR; serum miRNA
dc.titleCirculating microRNAs as noninvasive diagnostic biomarkers of liver disease in children with cystic fibrosis
dc.typeJournal article
pubs.publication-statusPublished

Files

Collections

Medicine publications