Novel markers for HCV-related HCC

但前提是。 在美国和欧洲，丙型肝炎病毒相关性肝细胞癌的发病率正在上升 而且很可能在未来10到20年内翻一番或翻两番。肝细胞癌的总体存活率很低，因为 大多数患者是在肿瘤处于晚期时被诊断出来的。我们小组已经开始了一项努力 整合基因组学、转录组学和蛋白质组学用于肝细胞癌的研究。我们还利用了一个 用蛋白质组学方法确定是否可以在血清中检测到不同的自身抗体谱系 并确定了一组不同的肿瘤抗原，它们在治疗过程中诱导体液反应 肝细胞癌的发展。我们的DNA/RNAIProtein1抗原集成方法为 在肝细胞癌发展中潜在重要的基因，以及识别新标记物的可能性 用于肝细胞癌的早期诊断。我们的方法也为本病的病因之间的联系提供了证据 潜在的肝病和肝细胞癌的发展模式。我们建议将基因组学和蛋白质学结合起来 丙型肝炎病毒相关肝细胞癌和丙型肝炎病毒差异表达基因和蛋白的鉴定方法 前驱病变。基因组和基于蛋白质组的分析的结合独特地允许描绘 转录和转录后调控导致的表达模式的全球变化，后 翻译修饰和蛋白质在细胞间的转移。它将允许识别 与肝细胞癌的发生发展相关的缺失表达的变化，其中一些可能与 肿瘤的外观。检测和验证这些潜在的标记需要高亲和力的探针 用于它们的检测和定量。为此，我们建议获得相应的抗体并 开发基于抗体的微阵列，以确定它们在血清中的水平以及它们对诊断肝细胞癌的效用。这个 使用微阵列实现这一效果提供了高通量、高灵敏度和低血清容量 需求，因此是非常有利的。我们将建立敏感性和特异性的 单独和组合的蛋白质生物标志物。肿瘤抗原板的鉴定 体液反应在癌症筛查和诊断中也可能有用。我们建议将流通领域 肿瘤抗原的抗体，这将使我们能够开发一种针对肝癌的血液测试。

PROVIDED. The incidence of HCV-associated hepatocellular carcinoma (HCC) is rising in the United States and Europe and is likely to double or triple over the next 10 to 20 years. The overall survival rate of HCC is poor because most patients are diagnosed when the tumor is in an advanced stage. Our group has embarked on an effort to integrate genomics, transcriptomics and proteomics for the profiling of HCC. We have also utilized a proteomic approach to determine whether a distinct repertoire of autoantibodies can be detected in the sera of HCC patients and identified a diverse set of tumor antigens that induce a humoral response during the development of HCC. Our integrated DNA/RNAIProteinlAntigen approach has provided new insights into genes that are potentially important in HCC development, as well as a potential for identifying new markers for early HCC diagnosis. Our approach also provided evidence for an association between the etiology of the underlying liver disease and patterns of HCC development. We propose to integrate genomic and proteomic approaches to identify genes and proteins that are expressed distinctively between HCV-related HCCs and precursor lesions. The combination of genomic and proteomic based profiling uniquely allows delineation of global changes in expression patterns resulting from transcriptional and post-transcriptional control, post- translational modifications and shifts in proteins between cellular compartments. It will allow the identification of changes in gone expression associated with the development of HCC, some of which may correlate with the appearance of the tumor. Testing and validation of these potential markers require high affinity probes for their detection and quantitation. For this purpose, we propose to acquire corresponding antibodies and to develop antibody-based microarrays to determine their level in sera and their utility for diagnosing HCC. The use of microarrays to this effect provides a high throughput high sensitivity and low serum volume requirement and therefore is highly advantageous. We will establish the sensitivity and specificity of the individual and combination of protein biomarkers. The identification of panels of tumor antigens that elicit a humoral response may also have utility in cancer screening and diagnosis. We propose to identify circulating antibodies to tumor antigens that will enable us to develop a blood test for HCC.