不同因素诱发的树齮肝癌组织的基因表达差异

Differentially Expressed Genes in Hepatocellular Carcinoma of Tree Shrew Induced by Different Factors

背景与目的:以往用基因芯片技术筛选肝癌相关基因的研究一般以癌旁组织作为对照与肝癌组织比较,但肝癌的癌旁组织常含有肝炎、肝硬化、增生结节等病变。为了探讨肝癌发生的分子机制及有关的基因改变,本研究用树齮动物模型对病因不完全相同的两组动物的肝癌和其自身的癌发生前活检肝组织进行基因表达水平的比较。方法:实验树齮分两组,黄曲霉素B1(aflatoxinB1,AFB1)组单纯喂AFB1,HBV+AFB1组先感染人乙型肝炎病毒(hepatitisBvirus,HBV),然后喂AFB1。实验期间定期抽血检查HBV感染标志,并剖腹取肝组织活检。动物出现肝癌后,两组各取2例肝癌组织及其冷冻保存的癌发生前活检肝组织,用cDNA微阵列技术检测、比较各例肝癌组织和其相应癌发生前活检肝组织的基因表达水平,分析不同病因的两组肝癌组织的差异表达基因的异同。结果:肝癌发生率在AFB1组和HBV+AFB1组分别为73.3%和77.8%。两组肝癌组织都有较大量的基因发生表达水平的改变,但在AFB1组以上调改变为主,在HBV+AFB1组以下调改变为主。在受测的588个(16个功能组)已知与人类肿瘤有关的基因中,两组有相同改变的基因共11个,它们主要分布在3个功能基因组,即凋亡相关蛋白组,DNA合成、修复和重组蛋白组以及生长因子、细胞因子和趋化因子组。结论:HBV对单纯AFB1引起的?

BACKGROUND &OBJECTIVE: Previous studies on differentially expressed genes in hepatocellular carcinoma (HCC) used to perform with para cancerous tissues as normal control. However, the para cancerous tissue of HCC is actually abnormal because they frequently contain hepatitis, cirrhosis, hyperplastic nodules or foci, etc. In order to explore the molecular mechanism and the responsible genes for hepatocarcinogenesis, through applying the HCC model of tree shrew (Tupaia belangeri chinensis), this study was designed to compare gene expression levels between HCC induced by different factors and their corresponding biopsies taken before HCC formation. METHODS: Tree shrews were divided into two groups. Group AFB1 was fed with aflatoxin B1 (AFB1). Group AFB1+HBV was infected firstly with human hepatitis B virus (HBV) and then fed with AFB1 as group AFB1. Serum tests for HBV markers and liver biopsies were performed periodically during the experiment. After appearance of HCC, 2 HCC samples from each group and their corresponding 30th week biopsies were tested respectively by cDNA microarray assay. The gene expression levels were compared between each HCC and the corresponding biopsies, and the differentially expressed genes from the two groups of HCC induced by different factors were analyzed. RESULTS: The incidence rates of HCC in group AFB1 and group AFB1+HBV were 73.3%and 77.8%, respectively. A considerable number of genes in both groups showed changes in their expression levels, which were mainly up regulated in group AFB1 but down regulated in group AFB1+HBV. On the other hand, among the 588 checked genes (16 functional classifications) that were known related to human cancer, 11 genes were similarly expressed in all of the 4 HCC from the two animal groups. Most of these 11 genes belonged functionally to 3 types, namely 'apoptosis associated protein','DNA synthesis,repair and recombination proteins', and 'growth factors, cytokines and chemokines'. CONCLUSION:(1)HBV can affect AFB1 induced gene expression in certain extent. (2)The gene expression profiles of HCC induced by different factors are different. (3)The common differentially expressed genes in these two HCC groups are worthwhile for further study as the possibly responsible genes for hepatocarcinogenesis.