HCC diagnostics defined by fucosylated serum biomarkers

描述（由申请人提供）：本提案的总体目标是开发一种新的肝细胞癌早期检测诊断方法，该方法基于检测患者血清中聚集水平升高的糖蛋白。我们与德雷塞尔大学的同事一起发现，核心聚焦水平的增加与肝癌的发展有关。糖基化模式的变化发生在癌症中，这一观察结果早前也被其他人报道过，然而，目前还没有开发出新的集中糖蛋白作为诊断。在我们早期的研究中，我们发现了一些具有高水平聚焦的糖蛋白，并验证了3个这样的蛋白，以进一步开发诊断。该I期的目标是开发一种凝集素elisa检测方法，并在一小群HCC患者中验证该检测方法。在II期研究中，将对该检测方法的特异性和敏感性进行评估，并与现有的HCC诊断检测方法进行比较，以获得批准新的HCC体外诊断检测方法所需的临床数据。这些目标的实现将允许引入一种高度敏感和特异性的诊断工具，用于HCC的早期检测。考虑到需要对HCC进行早期诊断，以促进早期干预，从而实现治愈，引入一种新的无创、高通量、高灵敏度和特异性的诊断方法是非常重要的，这种诊断方法基于高度聚焦的血清标志物。肝细胞癌（HCC）是世界范围内最常见的实体恶性肿瘤之一，在美国的发病率正在上升。大约三分之二的肝癌是HCC，这是最常见的恶性肿瘤之一。HCC病例数将继续增加，主要是由于丙型肝炎（HCV）流行。尽管医疗技术取得了进步，但1981年至1998年的5年生存率仅提高了3%，这可能是由于大多数HCC患者被诊断为晚期，导致美国的1年总生存率为25%。在HCC患者数量显著增加的背景下，早期发现和治疗对于改善预后至关重要。

DESCRIPTION (provided by applicant): The overall goal of this proposal is to develop a novel early detection diagnostic for hepatocellular carcinoma based on the detection of glycoproteins that have increased levels of fucosylation in the sera of patients. With our colleagues at Drexel University, we have shown that there is an increase in the level of core fucosylation associated with the development of liver cancer. The observation that changes in glycosylation patterns occur with cancer has been reported earlier by others as well, however, currently, no novel fucosylated glycoprotein is being developed as diagnostics. In our earlier studies, we identified a number of glycoproteins with elevated levels of fucosylation and validated 3 such proteins for further diagnostics development. The objectives of this phase I is to develop a Lectin-ELISA assay and validate the assay with a small cohort of patients diagnosed with HCC. In phase II, the specificity and sensitivity of the assay will be evaluated using a large serial and cross sectional patient population and compared with the existing diagnostic assay for HCC to generate clinical data needed for an approval of a new in vitro diagnostic test for HCC. Accomplishments of these aims will permit the introduction of a highly sensitive and specific diagnostic tool for the early detection of HCC. Given the need for early diagnosis for HCC to facilitate early intervention that can lead to a cure, the introduction of a new non-invasive, high through put and highly sensitive and specific diagnostic based on hyperfucosylated serum markers as described here is extremely important. Hepatocellular carcinoma (HCC) is 1 of the most common solid malignancies worldwide and the incidence in the United States is increasing. Approximately 2/3rds of all liver cancers are HCC, 1 of the most common aggressive malignancies. The number of cases of HCC will continue to increase primarily due to the hepatitis C (HCV) epidemic. Despite advances in medical technology, the 5-year survival between 1981 and 1998 improved only 3%, likely due to the fact that the majority of patients with HCC are diagnosed at advanced stages leading to an overall 1-year survival of 25% in the United States. In this setting of a significant increase in the number of patients with HCC, early detection and treatment are vital to improve outcome.