MicroRNA Signature at the Time of Clinical HCV Recurrence Associates With Aggressive Fibrosis Progression Post‐Liver Transplantation. Issue 3 (11th January 2013)

• Record Type: Journal Article
• Authors: Gehrau, R. C.; Mas, V. R.; Villamil, F. G.; Dumur, C. I.; Mehta, N. K.; Suh, J. L.; Maluf, D. G.
• Is Part Of: American journal of transplantation. Volume 13:Issue 3(2013:Mar.)
• Page Start: 729
• Page End: 737
• Publication Date: 2013-01-11
• Subjects: Transplantation of organs, tissues, etc -- Periodicals; 617.95
• DOI: 10.1111/ajt.12047
• Languages: English
• ISSNs: 1600-6135

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Diagnosis and prediction of the severity of hepatitis C virus recurrence (HCV<italic>rec</italic>) after liver transplantation (LT) remain a challenge. MicroRNAs have been recently recognized as potential disease biomarkers. Archival liver biopsy samples from 43 HCV+ LT recipients were collected at clinical HCV<italic>rec</italic> time and at 3 years post‐LT. Patients were classified as progressors (P = F0/F1) or nonprogressors (NP = F3/F4) according to the severity of fibrosis on the 3‐year biopsy. Training (n = 27) and validation (n = 16) sets were defined. RNA was isolated from all biopsies at clinical HCV<italic>rec</italic> time, labeled and hybridized to miRNA‐arrays. Progressors versus nonprogressors were compared using the two‐sample <italic>t</italic>‐test. A p‐value ≤0.01 was considered significant. The ingenuity pathway analysis tool was used for microRNA and miRNA:mRNA ontology data integration. Nine microRNAs were differentially expressed between groups. A supervised cluster analysis separated samples in two well‐defined groups (progressors vs. nonprogressors). Pathway analysis associated those microRNAs with hepatitis, steatosis, fibrosis, cirrhosis and T cell‐related immune response. Data integration identified 17 genes from a previous genomic study as 9‐microRNAs signature targets. Seven microRNAs were successfully validated in the validation set using QPCR. We have identified a 9‐microRNA signature able to identify early post‐LT patients at high risk of severe HCV<italic>rec</italic> during long‐term follow‐up.</p> </abstract>