GENE EXPRESSION PROFILE IN HEPATOCELLULAR CARCINOMA

HCC被认为是一种绝症，目前在发现有效的治疗方法方面进展甚微，导致其衰退。这主要是由于缺乏早期诊断的方法和缺乏与HCC发展相关的表型变化的信息。在HCC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HCC诊断和预后价值的新标志物。对这些基因的分析将有助于进一步了解肝癌的发生，并为hcc定向分子治疗的设计策略提供进一步的见解。现在，我们正在使用SAGE来探索在原代人肝细胞中被HBx或HC-core失调的潜在细胞基因。具体来说，我们计划确定一组潜在的基因，其表达在健康供者的原代肝细胞中是特异性的（即肝细胞与成纤维细胞），并受到HBx或HC-core的异常调节。目的基因的表达变化被用来与hbx阳性或hcv阳性HCC的基因表达谱进行比较。这种方法将使我们能够识别与HBV和hcv介导的肿瘤发生相关的潜在基因。我们还利用NCI人类肿瘤芯片基因微阵列来比较来自中国上海的原发性HCC和转移性HCC的表达谱。这些数据将用于比较来自不同地理区域的不同HBV或HCV状态的HCC的基因表达模式，并确定它们在HCC从原发性肿瘤到转移性病变过程中的变化模式。我们目前正在检查来自美国的HCC样本的基因表达谱。来自美国的肝细胞癌样本目前正在通过由美国国家癌症研究所资助的合作人体组织网络收集。- SAGE，微阵列，肝细胞癌，乙型肝炎病毒，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.