Quantitative RT-PCR in cirrhotic nodules reveals gene expression changes associated with liver carcinogenesis
Quantitative RT-PCR in cirrhotic nodules reveals gene expression changes associated with liver carcinogenesis
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DOI：
10.1002/path.1451
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发表时间：
2003-10-01
影响因子：
7.3
通讯作者：
Bedossa, P
中科院分区：
文献类型：
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作者：
Colombat, M;Paradis, V;Bedossa, P
肝硬化被认为是大多数肝细胞癌的前兆。为了深入了解肝癌发生的早期分子机制，本研究使用实时定量逆转录聚合酶链反应（RT-PCR）比较了31个选定基因在正常肝脏、肝硬化结节和肝细胞癌中的表达水平。由于肝硬化是由多克隆和单克隆结节混合组成，因此根据肝硬化结节的克隆状态也比较了基因表达水平。与正常肝脏相比，所研究的31个基因中有8个（NEGF2、ANGPT1、ARF、KRT19、SFN、CLDN4、MMP7和ETV4）在肝硬化结节中的表达显著增加，而只有1个（LYVEI）表达降低。在肝硬化和肝细胞癌中，除了KRT19，所有这些基因的变异趋势都是相同的。根据肝硬化结节的克隆状态比较基因表达变异时，只有LYVEI表达水平有显著差异。LYVE1基因表达水平从多克隆肝硬化结节到单克隆肝硬化结节（多克隆结节0.39 +/- 0.25；单克隆结节0.20 +/- 0.14,p < 0.05）和肝细胞癌（0.07 +/- 0.1）逐渐降低。总之，本研究强调了一个事实，即在肝细胞癌中强烈失调的基因中，一些已经在肝硬化中异常表达。其中一种基因LYVEI表达水平的降低与肝硬化结节的单克隆性有关。版权所有：John Wiley Sons， Ltd。
Cirrhosis is considered to be the precursor of most hepatocellular carcinomas. To gain insight into the early molecular mechanisms of liver carcinogenesis, this study compared, using real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), the expression levels of 31 selected genes in normal livers, cirrhotic nodules, and hepatocellular carcinomas. Since cirrhosis is composed of a mixture of polyclonal and monoclonal nodules, gene expression levels were also compared according to the clonal status of the cirrhotic nodules. The expression of eight of the 31 genes studied was significantly increased (NEGF2, ANGPT1, ARF, KRT19, SFN, CLDN4, MMP7, and ETV4) in cirrhotic nodules compared with normal liver, while only one was decreased (LYVEI). The same trend of variation was observed in cirrhosis and hepatocellular carcinomas for all of these genes except KRT19. When gene expression variation was compared according to the clonal status of cirrhotic nodules, only the LYVEI expression level was significantly different. The LYVE1 gene expression level decreased progressively from polyclonal cirrhotic nodules to monoclonal cirrhotic nodules (polyclonal nodules 0.39 +/- 0.25; monoclonal nodules 0.20 +/- 0.14; p < 0.05) and to hepatocellular carcinoma (0.07 +/- 0.1). In conclusion, this study highlights the fact that among genes strongly dysregulated in hepatocellular carcinoma, some are already abnormally expressed in cirrhosis. The decrease in the expression level of one of these genes, LYVEI, was associated with monoclonality in cirrhotic nodules. Copyright (C) 2003 John Wiley Sons, Ltd.