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: R C Gehrau, V R Mas, F G Villamil, C I Dumur, N K Mehta, J L Suh, D G Maluf
• Journal: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons (Am J Transplant) Vol. 13 Issue 3 Pg. 729-37 (Mar 2013) ISSN: 1600-6143 [Electronic] United States
• PMID: 23312020 (Publication Type: Journal Article)
• Copyright: © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.

Chemical References

• Biomarkers
• MicroRNAs
• RNA, Messenger

Topics

• Adult
• Aged
• Biomarkers (analysis, metabolism)
• Disease Progression
• Female
• Follow-Up Studies
• Gene Expression Profiling
• Graft Rejection
• Graft Survival
• Hepacivirus (pathogenicity)
• Hepatitis C (complications, surgery, virology)
• Humans
• Liver Cirrhosis (complications, diagnosis, etiology, surgery, virology)
• Liver Transplantation (adverse effects)
• Longitudinal Studies
• Male
• MicroRNAs (genetics)
• Middle Aged
• Oligonucleotide Array Sequence Analysis
• Postoperative Complications
• Prognosis
• Prospective Studies
• RNA, Messenger (genetics)
• Real-Time Polymerase Chain Reaction
• Recurrence
• Retrospective Studies
• Reverse Transcriptase Polymerase Chain Reaction
• Risk Factors