Differential transcriptome patterns for acute cellular rejection in recipients with recurrent hepatitis C after liver transplantation.
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 hepatitis C virus-positive recipients. The clinicopathological diagnosis based on biopsy examination was ACR-predominant with superimposed RHC in 9 samples (ACR group) and RHC without ACR (non-ACR group) in 13. Using oligonucleotide microarrays, we compared the transcriptional changes in the 2 groups and selected 2206 genes that were significantly modulated in ACR. We analyzed the regulatory networks in ACR with Ingenuity Pathway Analysis software, and we confirmed with quantitative real-time polymerase chain reaction the reproducibility of caspase 8, apoptosis-related cysteine peptidase and bone morphogenetic protein 2 up-regulation in another group of validation samples, representing 2 genes from the core network as the target genes for ACR. Our results demonstrated novel transcriptome patterns for ACR with concurrent RHC that were distinct from those of recipients with only RHC, suggesting that gene expression profiling may be useful in the diagnosis of ACR in recipients with hepatitis C.
Asaoka
Tadafumi
T
Department of Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
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
D000208:Acute Disease; D000328:Adult; D000368:Aged; D001706:Biopsy; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics; D053181:Caspase 8 / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D005820:Genetic Testing; D006084:Graft Rejection / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology / Q000821:virology; D006526:Hepatitis C / Q000150:complications / Q000175:diagnosis / Q000235:genetics / Q000601:surgery*; D006801:Humans; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D050778:NFATC Transcription Factors / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D053633:Receptor, Interferon alpha-beta / Q000235:genetics; D053707:Receptors, Interleukin-12 / Q000235:genetics; D012008:Recurrence; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016896:Treatment Outcome
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; C507964:IFNAR1 protein, human; C508439:IL12RB2 protein, human; D050778:NFATC Transcription Factors; C494008:NFATC3 protein, human; D053707:Receptors, Interleukin-12; D053633:Receptor, Interferon alpha-beta; C505530:CASP8 protein, human; D053181:Caspase 8