Genomics of liver cells anォ liver cancer cells

肝细胞和肝癌细胞的基因组学

• 批准号: 11307010
• 负责人: KOBAYASHI Kenichi
• 金额: $ 19.34万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11307010/
• 关键词: hepatocellularcarcinoma; Genomics; SAGE; DNAmicroarray; geneexpressionprofile; clusteranalysis; SAGE; DNAチップ; 遺伝子発現パターン; 肝臓特異的DNAチップ; DNA microarray

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inducible genes and oxidative stress-inducible genes were identified in both the CH-C and HCC libraries, and some unpublished new genes were specifically up- or down-regulated in the HCC library.DNA micro array containing 1,080 genes covering various categories of genes including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.

应用SAGE（serialanalysisofgene expression）方法分析了正常肝、慢性丙型肝炎（CH-C）肝组织和肝癌（HCC）组织的基因表达谱。从正常组织中共分离出30，982个序列标签，其中8，596个标签来自独特基因。在正常肝脏中高度表达的基因是那些编码血浆蛋白（>21.8%的总转录物）、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%）。约13.9%的转录本编码的基因尚未在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文库和HCC文库中均发现了IFN-γ诱导基因和氧化应激诱导基因的上调表达，并发现了一些未发表的新基因在HCC文库中特异性上调或下调表达。基因表达谱的层次聚类分析显示，B型和C型肝炎病毒感染，而不是年龄，性别或肝炎组织学，是决定聚类的重要因素（P 0.05）。在B型肝炎组织病变中，参与炎症反应的基因占优势，而在丙型肝炎中，抗炎反应基因的表达相对占优势。此外，DNA微阵列数据的聚类分析表明，肿瘤标志物甲胎蛋白产生肝癌细胞系共享不同类别的基因的共同表达谱。肝癌组织基因表达谱分析表明，某些基因具有与肿瘤分化程度相关的特征性基因表达谱。

项目成果

Taro Yamashita: "Comprehensive gene expression profile of a normal human liver"Biochemical and Biophysical Research Communications. (in press).

山下太郎：“正常人类肝脏的综合基因表达谱”生物化学和生物物理研究通讯。

Katsuro Koike: "Survey of hepatitis B virus co-infection in hepatitis C virus infected patients suffering from chronic hepatitis and hepatocellular carcinoma in Japan"Japanese Journal of Cancer Research. 90. 1270-1272 (1999)

小池胜郎：“日本慢性肝炎和肝细胞癌丙型肝炎病毒感染者中乙型肝炎病毒合并感染的调查”日本癌症研究杂志。

Shirota Y et al.: "Identification of differential expressed genes in hepatocellular carcinoma with cDNA microarrays"Hepatology. 33・4. 832-840 (2001)

Shirota Y等：“利用cDNA微阵列鉴定肝细胞癌中的差异表达基因”Hepatology 832-840(2001)。

Shirota Y et al.: "Identification of differential expressed genes in hepatocellular carcinoma with cDNA micoarrys"Hepatology. 33・4. 832-840 (2001)

Shirota Y等：“用cDNA微阵列鉴定肝细胞癌中的差异表达基因”Hepatology 832-840（2001）。

Shirora,Y.,Kaneko,S.,Honda,M.,Kawai,H.F.,Kobayashi,K.: "Identification of differentially expressed genes in hepatocellular carcinoma with cDNA microarrays"Hepatology in print. 33・4. (2001)

Shirora, Y.、Kaneko, S.、Honda, M.、Kawai, H.F.、Kobayashi, K.：“利用 cDNA 微阵列鉴定肝细胞癌中的差异表达基因”，《肝病学》印刷版 (2001)。