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MicroRNA Signature at the Time of Clinical HCV Recurrence Associates With Aggressive Fibrosis Progression Post‐Liver Transplantation
Author(s) -
Gehrau R. C.,
Mas V. R.,
Villamil F. G.,
Dumur C. I.,
Mehta N. K.,
Suh J. L.,
Maluf D. G.
Publication year - 2013
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.12047
Subject(s) - medicine , microrna , cirrhosis , liver biopsy , fibrosis , hepatitis c , liver transplantation , hepatitis c virus , steatosis , transplantation , biopsy , fold change , gene signature , oncology , gastroenterology , immunology , virus , gene , gene expression , biology , biochemistry
Diagnosis and prediction of the severity of hepatitis C virus recurrence (HCV rec ) 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 rec 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 rec time, labeled and hybridized to miRNA‐arrays. Progressors versus nonprogressors were compared using the two‐sample t ‐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 rec during long‐term follow‐up.