MicroRNA signature at the time of clinical HCV recurrence associates with aggressive fibrosis progression post-liver transplantation

R. C. Gehrau, Valeria Mas, F. G. Villamil, C. I. Dumur, N. K. Mehta, J. L. Suh, Daniel Maluf

Research output: Contribution to journalArticle

18 Citations (Scopus)

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. The authors use tissue microarray analyses to determine a 9-microRNA signature able to identify hepatitis C patients at greater risk of severe disease recurrence and worse outcome post-liver transplantation.

Original languageEnglish (US)
Pages (from-to)729-737
Number of pages9
JournalAmerican Journal of Transplantation
Volume13
Issue number3
DOIs
StatePublished - Mar 1 2013

Fingerprint

MicroRNAs
Liver Transplantation
Fibrosis
Recurrence
Hepacivirus
Biopsy
Tissue Array Analysis
Hepatitis C
Hepatitis
Cluster Analysis
Biomarkers
RNA
T-Lymphocytes
Messenger RNA
Liver

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

Cite this

MicroRNA signature at the time of clinical HCV recurrence associates with aggressive fibrosis progression post-liver transplantation. / Gehrau, R. C.; Mas, Valeria; Villamil, F. G.; Dumur, C. I.; Mehta, N. K.; Suh, J. L.; Maluf, Daniel.

In: American Journal of Transplantation, Vol. 13, No. 3, 01.03.2013, p. 729-737.

Research output: Contribution to journalArticle

@article{5d0706f09be942aebd11a4dc33f62202,
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. The authors use tissue microarray analyses to determine a 9-microRNA signature able to identify hepatitis C patients at greater risk of severe disease recurrence and worse outcome post-liver transplantation.",
author = "Gehrau, {R. C.} and Valeria Mas and Villamil, {F. G.} and Dumur, {C. I.} and Mehta, {N. K.} and Suh, {J. L.} and Daniel Maluf",
year = "2013",
month = "3",
day = "1",
doi = "10.1111/ajt.12047",
language = "English (US)",
volume = "13",
pages = "729--737",
journal = "American Journal of Transplantation",
issn = "1600-6135",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - MicroRNA signature at the time of clinical HCV recurrence associates with aggressive fibrosis progression post-liver transplantation

AU - Gehrau, R. C.

AU - Mas, Valeria

AU - Villamil, F. G.

AU - Dumur, C. I.

AU - Mehta, N. K.

AU - Suh, J. L.

AU - Maluf, Daniel

PY - 2013/3/1

Y1 - 2013/3/1

N2 - 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. The authors use tissue microarray analyses to determine a 9-microRNA signature able to identify hepatitis C patients at greater risk of severe disease recurrence and worse outcome post-liver transplantation.

AB - 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. The authors use tissue microarray analyses to determine a 9-microRNA signature able to identify hepatitis C patients at greater risk of severe disease recurrence and worse outcome post-liver transplantation.

UR - http://www.scopus.com/inward/record.url?scp=84874400437&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84874400437&partnerID=8YFLogxK

U2 - 10.1111/ajt.12047

DO - 10.1111/ajt.12047

M3 - Article

VL - 13

SP - 729

EP - 737

JO - American Journal of Transplantation

JF - American Journal of Transplantation

SN - 1600-6135

IS - 3

ER -