Genomics of liver cells anォ liver cancer cells

采用SAGE （serial analysis of Gene expression）方法分析正常肝脏、慢性丙型肝炎（CH-C）和肝癌（HCC）组织的基因表达谱。共从正常组织中分离出30,982个序列标签，其中8,596个标签来自独特基因。在正常肝脏中高表达的基因是编码血浆蛋白（>占总转录本的21.8%）、细胞质蛋白（>8.6%）、酶（>4.8%）、蛋白酶抑制剂（>1.7%）、补体(>1.1！%)，凝血因子（>0.75%）。迄今为止，约有13.9%的转录本编码的基因未在GenBank中报道。与CH-C和NL文库相比，HCC文库中的标签显示出许多差异表达基因的存在。在CH-C和HCC文库中均发现ifn - γ诱导基因和氧化应激诱导基因的上调，一些未发表的新基因在HCC文库中特异性上调或下调。最初开发了包含1080个基因的DNA微阵列，涵盖了致癌基因、肿瘤抑制基因、细胞凋亡相关基因、细胞周期相关基因等不同类别的基因。基因表达谱的分层聚类分析显示，乙型和丙型肝炎病毒感染是决定聚类的重要因素，而年龄、性别或肝炎组织学无关（p0.05）。在乙型肝炎组织病变中，参与炎症的基因占主导地位，而在丙型肝炎中，抗炎反应基因的表达相对占优势。此外，DNA微阵列数据聚类分析显示，肿瘤标志物甲胎蛋白产生肝癌细胞系在不同类别中具有共同的基因表达谱。肝癌组织的基因表达谱分析显示，部分基因根据肿瘤分化具有特征性的基因表达模式。

Gene expression profile of normal liver, liver tissue from chronic hepatitis C (CH-C) and liver cancer (HCC) were analyzed by SAGE (serial analysis of gene expression) method. Total of 30,982 sequence tags were separated from normal tissue, in which 8,596 tags were derived from unique genes. The genes highly expressed in the normal liver were those encoding plasma proteins (>21.8% of total transcripts), cytoplasmic proteins (>8.6%), enzymes (>4.8%), protease inhibitors (>1.7%), complements (>1.1!%), and coagulation factors (>0.75%). About 13.9% of all transcripts encoded genes not reported in GenBank thus far. Tags from the HCC library exhibited the existence of many differentially expressed genes compared with those from the CH-C and NL libraries. Up-regulation of IFN-gamma inducible genes and oxidative stress-inducible genes were identified in both the CH-C and HCC libraries, and some unpublished new genes were specifically up- or down-regulated in the HCC library.DNA micro array containing 1,080 genes covering various categories of genes including oncogenes, tumor suppressor genes, apoptosis related genes, cell cycle related genes were originally developed. Hierarchical clustering analysis of the gene expression profiles showed that Hepatitis B and C virus infection, but not age, sex, or histology of hepatitis, were significant factors determining clustering (P 0.05). In hepatitis B tissue lesions, genes involved in inflammation were predominant, whereas in hepatitis C, expression of anti-inflammatory response genes was relatively dominant. In addition, clustering analysis of DNA micro array data showed that tumor marker alpha-fetoprotein producing hepatoma cell lines shares common expression profile of genes in various categories. Analysis of gene expression profile of HCC tissues showed that some genes had characteristic gene expression pattern according to tumor differentiation.