GENE EXPRESSION PROFILE IN HEPATOCELLULAR CARCINOMA

肝癌被认为是一种晚期疾病，目前在发现导致其衰退的有效治疗方法方面进展甚微。这在很大程度上是由于缺乏早期诊断的方法，以及缺乏与肝细胞癌发展相关的表型变化的信息。肝细胞癌发生过程中基因表达的变化在很大程度上是未知的。识别基因表达谱的努力将有助于建立具有潜在诊断和预后价值的新的标记。对这些基因的分析将进一步了解肝癌的发生机制，并为设计肝癌导向的分子治疗策略提供进一步的见解。现在，我们正在使用SAGE来探索在原代人类肝细胞中受HBx或HC-core调控的潜在细胞基因。具体地说，我们计划确定一组潜在的基因，它们在来自健康捐赠者的原代肝细胞中表达是特异的(即，肝细胞与成纤维细胞)，并受到HBx或HC-core的异常调节。所揭示的感兴趣基因的表达变化被用于与HBx阳性或丙型肝炎阳性肝细胞癌的基因表达谱进行比较。这一方法将使我们能够识别与乙肝病毒和丙型肝炎病毒介导的肿瘤发生相关的潜在基因。我们还利用美国国立卫生研究院人类癌芯片基因芯片比较了来自上海的原发性肝癌和转移性肝癌的表达谱，中国。这些数据将被用来比较不同地理区域不同乙肝病毒或丙型肝炎病毒状态的肝细胞癌的基因表达模式，并确定它们在从原发肿瘤向转移灶发展过程中的变化模式。我们目前正在检查来自美国的肝细胞癌样本的基因表达谱。来自美国的肝癌样本目前正通过合作的人体组织网络收集，该网络由国家癌症研究所资助。-SAGE，微阵列，肝细胞癌，乙肝病毒，丙型肝炎病毒，-人体组织，液体，细胞等

HCC is considered to be a terminally-ill disease and currently there is little progress toward the discovery of efficient therapies leading to its recession. This is largely due to the lack of a method for an earlier diagnosis and the lack of information on the phenotypic changes associated with the development of HCC. Changes in gene expression during the genesis of HCC are largely unknown. Efforts to identify gene expression profiles will contribute to the establishment of novel markers with potential diagnostic and prognostic value for HCC. Analysis of these genes would provide further understanding of the genesis of liver cancer and provide further insights into designing strategies for HCC-directed molecular therapy. Now we are using SAGE to explore the potential cellular genes that are disregulated in primary human hepatocytes by HBx or HC-core. Specifically, we plan to identify a potential group of genes whose expressions are specifically (i.e., hepatocytes vs. fibroblasts) and abnormally regulated by HBx or HC-core in primary hepatocytes derived from healthy donors. The revealed expression changes in the genes of interest are used to compare with the gene expression profile from HBx-positive or HCV-positive HCC. This approach would allow us to identify potential genes that are related to HBV and HCV-mediated oncogenesis. We are also utilizing the NCI Human OncoChip Genes microarray to compare the expression profiles in primary HCC and metastatic HCC from Shanghai, China. These data will be used to compare the gene expression patterns of HCC from different geographic areas that differ in the status of HBV or HCV, and to identify their change patterns during the progression from primary tumors to metastatic lesions of HCC. We are currently examining gene expression profiles of HCC samples from the US. The HCC samples from the US are currently being collected through the cooperative Human Tissue Network, funded by the National Cancer Institute. - SAGE, microarray, hepatocellular carcinoma, hepatitis B virus, hepatitis C virus, - Human Tissues, Fluids, Cells, etc.