Novel Reagents For The Detection Of Low Abundance Cancer Specific Glycoforms

描述（由申请人提供）：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。据估计，到2020年，HCC病例数将继续增加81%（从每年约13,000例的基线开始），主要原因是丙型肝炎（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%。肝细胞癌的早期诊断将有助于改善预后。特异性血清生物标志物蛋白的n -链糖基化变化随着肝癌的发展而发生。该资助的具体目标是开发高亲和力结合凝集素（碳水化合物结合蛋白），识别HCC血清生物标志物上发生的糖基化变化（specific Aim 1），并在基于ELISA的格式中使用这些重组凝集素，以检测其预测肝脏疾病和HCC的敏感性和特异性（specific Aim 2）。

DESCRIPTION (provided by applicant): Hepatocellular carcinoma (HCC) is one of the most common solid malignancies worldwide and the incidence in the United States is increasing. It has been estimated that the number of cases of HCC will continue to increase by 81% (from a baseline of about 13,000 a year) by the year 2020, 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. Early diagnosis of HCC in patients at risk for liver disease will help improve outcome. N-linked glycosylation changes of specific serum biomarker proteins occur with the development of liver cancer. The specific aims of this grant are focused on developing high affinity binding lectins (carbohydrate binding proteins) that recognize the glycsoylation changes that occur on serum biomarkers of HCC (Specific Aim 1) and using these recombinant lectins in an ELISA based format on archived patient serum samples to test their sensitivity and specificity for predicting liver disease and HCC (Specific Aim 2). PUBLIC HEALTH RELEVANCE: The incidence of hepatocellular carcinoma (HCC) is increasing worldwide with a poor prognosis for survival related to the lack of predictive assays for early detection. Sensitive, specific, non-invasive assays that are predictive for diagnosing HCC in patients at risk for liver disease are urgently needed.