Differential Transcriptome Patterns for Acute Cellular Rejection in Recipients with Recurrent Hepatitis C After Liver Transplantation
Differential Transcriptome Patterns for Acute Cellular Rejection in Recipients with Recurrent Hepatitis C After Liver Transplantation
复制标题
DOI：
10.1002/lt.21883
复制
发表时间：
2009-12-01
影响因子：
4.6
通讯作者：
Mori, Masaki
中科院分区：
文献类型：
--
作者：
Asaoka, Tadafumi;Kato, Tomoaki;Mori, Masaki
肝移植术后急性细胞排斥反应（ACR）和复发性丙型肝炎（RHC）诊断的标准程序仍然是肝脏活检的组织病理学评估。然而，丙型肝炎病毒阳性受体的ACR通常难以诊断，因为其变化与RHC相同且重叠。本研究的目的是确定RHC受体中ACR的潜在靶基因。我们分析了来自21名丙型肝炎病毒阳性受体的22份肝活检样本。基于活检检查的临床病理诊断为ACR为主合并RHC 9例（ACR组），无ACR的RHC 13例（非ACR组）。利用寡核苷酸微阵列，我们比较了两组的转录变化，并选择了2206个在ACR中被显著调节的基因。我们利用Ingenuity Pathway Analysis软件分析了ACR的调控网络，并通过实时定量聚合酶链反应证实了caspase 8、凋亡相关半胱氨酸肽酶和骨形态发生蛋白2上调在另一组验证样品中的可重复性，代表了核心网络中的2个基因作为ACR的靶基因。我们的研究结果显示，ACR并发RHC的转录组模式与仅RHC的受体不同，这表明基因表达谱可能有助于丙型肝炎受体ACR的诊断。(c) 2009年。
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. Liver Transpl 15.1738-1749, 2009. (C) 2009 AASLD.