Unknown,Transcriptomics,Genomics,Proteomics

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Transcriptome patterns for Acute Cellular Rejection in Recipients with Recurrent Hepatitis C after Liver Transplantation

ABSTRACT: The histological evaluation of liver via biopsy remains as the standard for the diagnosis of both acute cellular rejection (ACR) and recurrent hepatitis C (RHC) after liver transplantation. Nevertheless, it is often difficult to diagnose ACR in HCV-positive recipients because of common co-existing and overlapping morphological changes with RHC. The aim of the study was to identify potential target genes for ACR in recipients with RHC. We analyzed 22 liver biopsy samples obtained from 21 HCV-positive recipients. The clinicopathological diagnoses for the biopsies were ACR-predominant with superimposed RHC in 9 samples (ACR group) and RHC with no ACR (non-ACR group) in the remaining. We compared the transcriptional alterations between the two groups with oligonucleotide microarray and selected 2206 genes which were significantly modulated in ACR. Subsequently we analyzed the regulatory networks in ACR using Ingenuity Pathway Analysis, and focused on 5 genes (IFNAR1, IL-12RB2, NFATC3, BMP2, and CASP8) from the core network as the target genes for ACR. In conclusion, our results demonstrated that novel transcriptome patterns of ACR and concurrent RHC were present and distinct from recipients with only RHC, suggesting that gene expression profiling may have a role in the diagnosis of ACR in recipients with hepatitis C. Keywords: Gene identification in ACR with recurrent HCV infection Of 22 liver biopsy samples, 9 represented the clinicopathological diagnoses for ACR-predominant with superimposed RHC (ACR group) and 13 represented the clinicopathological diagnoses for RHC with no ACR (non-ACR group) .

ORGANISM(S): Homo sapiens

SUBMITTER: Tadafumi Asaoka

PROVIDER: E-GEOD-13440 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Differential transcriptome patterns for acute cellular rejection in recipients with recurrent hepatitis C after liver transplantation.

Asaoka Tadafumi T Kato Tomoaki T Marubashi Shigeru S Dono Keizo K Hama Naoki N Takahashi Hidenori H Kobayashi Shogo S Takeda Yutaka Y Takemasa Ichiro I Nagano Hiroaki H Yoshida Hideo H Ruiz Phillip P Tzakis Andreas G AG Matsubara Kenichi K Monden Morito M Doki Yuichiro Y Mori Masaki M

Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society 20091201 12

Histopathological evaluation of the liver via biopsy remains the standard procedure for the diagnosis of both acute cellular rejection (ACR) and recurrent hepatitis C (RHC) after liver transplantation. Nevertheless, it is often difficult to diagnose ACR in hepatitis C virus-positive recipients because of changes in common and overlapping with RHC. The aim of this study was to identify potential target genes for ACR in recipients with RHC. We analyzed 22 liver biopsy samples obtained from 21 hepa ...[more]

PMID: 19938108

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Project description:Background & Aims. The current staging system for colorectal cancer (CRC) based on TNM classification allows prediction of potential recurrence. However, it does not necessarily make reliable personalized prediction of prognosis. In this paper we describe combination of clinicopathological data and gene signature of dissected tumor specimen with stage II and III CRC patients would improve the situation.. Methods. A total of 1978 CRC were collected over 5 years, and then 371 stage II and 322 stage III of them with more than 45.9 months records were subjected to clinicopathological feature analyses. Out of this collection, 129 stage II and III CRC cases were selected for analyses of gene expression profiles with resected specimen. The gene signatures were analyzed by repeated random divisions of the samples into training and test sets to extract discriminator genes. After testing the applicability of this discriminator set, it was subjected to validation using a newly obtained set of 69 samples. Results. The pathological factors in solo or in combinations could not make personalized recurrence prediction, except for partial success with stage II patients. The gene signature, on the other hand, was capable of producing a set of discriminator genes, though the accuracy was yet to be improved. We observed that the best result was obtained when discriminators were selected from stage II CRC samples and used for prognosis of stage II CRC. When stage III cases were included in the process of discriminator extraction or in the process to validate samples, the results were poorer. Finally, we examined 31 independent stage II samples with a set of 30 such discriminators and were able to obtain results with 78 % accuracy, 90 % negative predictive value (NPV), and 55% positive predictive value (PPV). Conclusions. Independent clinicopathological variables were not able to predict prognosis of individual patient, unless the factors are combined. On the other hand, gene signatures allowed accurate prediction of prognosis for individuals, especially with stage II CRC, suggesting its potential use for selection of best treatment option for individual patients. The accuracy of discriminator prediction will be further improved when we take the evolution of CRC into consideration. Of 198 samples, 129 represented the discovery phase and 69 represented the validation phase.

Project description:Recurrent hepatitis C virus (rHCV) is universal post-liver transplantation (LT), with accelerated fibrosis rates compared to non-transplanted patients. rHCV is associated with increased mortality and morbidity post-transplant and is a leading indication for re-transplantation. We hypothesized that miRNA expression profiles from liver grafts can distinguish severity of HCV recurrence and differentiate this from acute cellular rejection (ACR). Methods Using microarrays, we characterized global microRNA (miRNA) expression from patients with slow HCV fibrosis progression (F<2 Ishak), fast HCV fibrosis progression (FM-bM-^IM-%2 Ishak), ACR and non-HCV transplanted patients. Selected miRNA were analysed by quantitative PCR (qPCR) using both liver tissue and serum samples. Results We demonstrated changes in miRNA expression in patients with slow HCV fibrosis progression that were anti-fibrogenic, anti-angiogenic and anti-inflammatory in comparison to patients with fast HCV fibrosis progression. miRNA-146a, miRNA-19a, miRNA- 20a and miRNA-let-7e expression were increased in the slow HCV fibrosis progression group. In addition, comparison of patients with fast HCV progression against patients with ACR identified pro-fibrogenic pathways. qPCR analysis on liver tissue and serum confirmed the up-regulation of miRNAs in the slow HCV fibrosis progression group. Conclusion We demonstrate specific miRNA expression signatures that distinguish rate of progression of HCV recurrence and ACR post M-bM-^@M-^Sliver transplantation. Pathway analysis indicates that specific miRNA may play a regulatory role in these processes. The miRNAs identified may act as potential biomarkers for HCV recurrence post-LT and help distinguish between ACR and recurrent HCV. We compared 29 patients in total; 11 patients with slow HCV fibrosis progression, 9 patients with fast HCV fibrosis progression, 5 patients with acute cellular rejection and 4 HCV negative patients with normal liver histology that acted as controls. RNA was extracted from archived histology samples of the RG and NRG and miRNA expression was analysed using the affymetrix Genechip miRNA 2.0 assays.

Dataset Information

Transcriptome patterns for Acute Cellular Rejection in Recipients with Recurrent Hepatitis C after Liver Transplantation

Publications

Differential transcriptome patterns for acute cellular rejection in recipients with recurrent hepatitis C after liver transplantation.

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