Pérez-Carreón Julio Isael, López-García Cristina, Fattel-Fazenda Samia, Arce-Popoca Evelia, Alemán-Lazarini Leticia, Hernández-García Sergio, Le Berre Véronique, Sokol Sergueï, Francois Jean Marie, Villa-Treviño Saúl
Departamento de Biología Celular, Centro de Investigación y de Estudios Avanzados del IPN, Mexico, DF, Mexico.
Neoplasia. 2006 May;8(5):373-83. doi: 10.1593/neo.05841.
In this study, we investigated the time course gene expression profile of preneoplastic nodules and hepatocellular carcinomas (HCC) to define the genes implicated in cancer progression in a resistant hepatocyte model. Tissues that included early nodules (1 month, ENT-1), persistent nodules (5 months, ENT-5), dissected HCC (12 months), and normal livers (NL) from adult rats were analyzed by cDNA arrays including 1185 rat genes. Differential genes were derived in each type of sample (n = 3) by statistical analysis. The relationship between samples was described in a Venn diagram for 290 genes. From these, 72 genes were shared between tissues with nodules and HCC. In addition, 35 genes with statistical significance only in HCC and with extreme ratios were identified. Differential expression of 11 genes was confirmed by comparative reverse transcription-polymerase chain reaction, whereas that of 2 genes was confirmed by immunohistochemistry. Members involved in cytochrome P450 and second-phase metabolism were downregulated, whereas genes involved in glutathione metabolism were upregulated, implicating a possible role of glutathione and oxidative regulation. We provide a gene expression profile related to the progression of nodules into HCC, which contributes to the understanding of liver cancer development and offers the prospect for chemoprevention strategies or early treatment of HCC.
在本研究中，我们调查了癌前结节和肝细胞癌（HCC）的时间进程基因表达谱，以确定在抗性肝细胞模型中与癌症进展相关的基因。对来自成年大鼠的组织进行了分析，这些组织包括早期结节（1个月，ENT-1）、持续性结节（5个月，ENT-5）、解剖的HCC（12个月）和正常肝脏（NL），使用包含1185个大鼠基因的cDNA阵列进行分析。通过统计分析在每种类型的样本（n = 3）中得出差异基因。在维恩图中描述了290个基因的样本间关系。其中，72个基因在有结节的组织和HCC之间共享。此外，还鉴定出35个仅在HCC中有统计学意义且具有极端比值的基因。通过比较逆转录-聚合酶链反应证实了11个基因的差异表达，而通过免疫组织化学证实了2个基因的差异表达。参与细胞色素P450和第二阶段代谢的成员下调，而参与谷胱甘肽代谢的基因上调，这暗示了谷胱甘肽和氧化调节的可能作用。我们提供了与结节进展为HCC相关的基因表达谱，这有助于理解肝癌的发展，并为化学预防策略或HCC的早期治疗提供了前景。
