title: MicroRNA signature at the time of clinical HCV recurrence associates with aggressive fibrosis progression post-liver transplantation.
abstract: Diagnosis and prediction of the severity of hepatitis C virus recurrence (HCVrec) 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 HCVrec 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 HCVrec 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 HCVrec during long-term follow-up.
authors: Transplant Division, Department of Surgery, University of Virginia, Charlottesville, VA, USA.
authors: R C
authors: RC
authors: Gehrau
authors: V R
authors: VR
authors: Mas
authors: F G
authors: FG
authors: Villamil
authors: C I
authors: CI
authors: Dumur
authors: N K
authors: NK
authors: Mehta
authors: J L
authors: JL
authors: Suh
authors: D G
authors: DG
authors: Maluf
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D006084:Graft Rejection; D006085:Graft Survival; D016174:Hepacivirus / Q000472:pathogenicity; D006526:Hepatitis C / Q000150:complications / Q000601:surgery* / Q000821:virology; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications / Q000175:diagnosis* / Q000209:etiology / Q000601:surgery* / Q000821:virology; D016031:Liver Transplantation / Q000009:adverse effects*; D008137:Longitudinal Studies; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011183:Postoperative Complications; D011379:Prognosis; D011446:Prospective Studies; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012008:Recurrence; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D035683:MicroRNAs; D012333:RNA, Messenger