Novel Reagents For The Detection Of Low Abundance Cancer Specific Glycoforms

描述(申请人提供)：肝细胞癌是世界上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，主要由于丙型肝炎(丙型肝炎)的流行，肝细胞癌的病例数量将继续增长81%(基线为每年约13,000例)。尽管医疗技术取得了进步，但1981至1998年间的5年存活率仅提高了3%，这可能是因为大多数肝细胞癌患者被诊断为晚期，导致美国总体1年存活率为25%。对有肝病风险的患者及早诊断肝细胞癌将有助于改善预后。随着肝癌的发展，特异性血清生物标志物蛋白的N-连锁糖基化发生变化。这笔赠款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)，识别发生在肝细胞癌血清生物标记物上的糖基化变化(特定目标1)，并在存档的患者血清样本中使用这些重组凝集素，以测试其预测肝病和肝细胞癌的敏感性和特异性(特定目标2)。 与公共卫生相关：世界范围内肝细胞癌的发病率正在增加，由于缺乏早期发现的预测性分析，生存预后很差。迫切需要灵敏的、特异的、非侵入性的检测方法来预测有肝病风险的患者的肝细胞癌。

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.