Molecular Signatures of Recurrent Hepatocellular Carcinoma Secondary to Hepatitis C Virus following Liver Transplantation.
Molecular Signatures of Recurrent Hepatocellular Carcinoma Secondary to Hepatitis C Virus following Liver Transplantation.
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DOI：
10.1155/2013/878297
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发表时间：
2013
影响因子：
2.5
通讯作者：
Perkins JD
中科院分区：
文献类型：
--
作者：
Das T;Diamond DL;Yeh M;Hassan S;Bryan JT;Reyes JD;Perkins JD
慢性丙型肝炎病毒（HCV）诱导的肝细胞癌（HCC）是肝移植（LT）的主要指征。在西方国家，肝移植后肝癌复发率估计在15%至20%之间，是死亡的主要原因。目前，没有标准的方法来治疗HCC复发的高风险患者。本研究的目的是调查HCC复发的分子特征，这可能导致未来对基因调控的研究，有助于新的治疗选择。选择了两组患者，一组包括肝移植后≤3年发生HCC复发（HCC-R）的HCV患者，第二组包括未发生HCC复发（HCC-NR）的HCV患者。在福尔马林固定石蜡包埋（FFPE）的肝脏组织中进行了包含超过29，000个已知基因的微阵列分析。基因表达谱分析显示两组间有194个差异表达基因。这些基因属于细胞网络，包括细胞周期G1/S检查点调节因子、RAN信号传导、慢性髓性白血病信号传导、癌症的分子机制、FXR/RXR激活和肝胆汁淤积。通过定量PCR分析，发现了一组与肝癌复发相关的分子标记，并验证了这些基因的表达水平。
Chronic hepatitis C virus (HCV) induced hepatocellular carcinoma (HCC) is a primary indication for liver transplantation (LT). In western countries, the estimated rate of HCC recurrence following LT is between 15% and 20% and is a major cause of mortality. Currently, there is no standard method to treat patients who are at high risk for HCC recurrence. The aim of this study was to investigate the molecular signatures underlying HCC recurrence that may lead to future studies on gene regulation contributing to new therapeutic options. Two groups of patients were selected, one including patients with HCV who developed HCC recurrence (HCC-R) ≤3 years from LT and the second group including patients with HCV who did not have recurrent HCC (HCC-NR). Microarray analysis containing more than 29,000 known genes was performed on formalin-fixed-paraffin-embedded (FFPE) liver tissue from explanted livers. Gene expression profiling revealed 194 differentially regulated genes between the two groups. These genes belonged to cellular networks including cell cycle G1/S checkpoint regulators, RAN signaling, chronic myeloid leukemia signaling, molecular mechanisms of cancer, FXR/RXR activation and hepatic cholestasis. A subset of molecular signatures associated with HCC recurrence was found. The expression levels of these genes were validated by quantitative PCR analysis.