Predicting HCC through Glycomics

通过糖组学预测 HCC

基本信息

批准号：
8777752
负责人：
Anand S. Mehta
金额：
$ 2.26万
依托单位：
DREXEL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-08-01 至 2015-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8777752
关键词：
AFP gene Address Aleuria aurantia lectin Americas Antibodies Behavior Binding Biological Assay Biological Markers Blinded Cervical Cancer Screening Cirrhosis Clinical Management Complement Detection Development Diagnosis Early Detection Research Network Fucose Glycoproteins Goals Grant Hemopexin Human Individual Inflammation Kininogens Lead Lectin Liver diseases Malignant Neoplasms Malignant neoplasm of liver Measures Methodology Methods Morbidity - disease rate Patients Pattern Performance Polysaccharides Population Primary carcinoma of the liver cells Proteins Qualifying Reagent Recombinants Research Project Grants Sampling Screening for Hepatocellular Cancer Serum Specificity Survival Rate Testing Two-Dimensional Gel Electrophoresis United States Validation Work alpha 1-Antitrypsin alpha-Fetoproteins arm base cohort glycosylation improved malignant breast neoplasm novel success

项目摘要

DESCRIPTION (provided by applicant): The hypothesis of the original grant was that fucosylation increases with the development of hepatocellular carcinoma (HCC) and that fucosylated glycoprotein(s) will make sensitive and specific markers of HCC. This hypothesis has been confirmed and in our analysis of over 1000 patient samples, we have clearly shown that fucosylated glycoproteins can make sensitive and specific markers of HCC, either alone or in combination with other markers. However, in our analysis, we have determined that in addition to core fucosylation there are many other changes that occur with liver disease. Some of these changes are cancer specific and can be used to complement our existing markers, while others can occur with just liver disease (inflammation) and lead to false positives. Thus in aim 1, we will develop novel and unique reagents that will dramatically improve our assays and continue our discovery efforts to find biomarkers that can be used clinically for the management of HCC. In aim 2 we will utilize our new lectins and continue our discovery efforts in an effort to find new biomarkers in biomarker negative populations that can complement our existing markers and lead to 100% sensitivity and 100% specificity. Finally in aim 3, we will test our lead markers in a NCI sponsored study comprising of over 350 cases of HCC and which we pre-qualified for. At the end of this 5 year period we will have validated our biomarkers and definitively proved our hypothesis that fucosylated proteins can make sensitive and specific markers of HC.

描述（由申请人提供）：最初资助的假设是岩藻糖基化随着肝细胞癌（HCC）的发展而增加，并且岩藻糖基化糖蛋白将成为 HCC 的敏感和特异性标记物。这一假设已得到证实，并且在我们对 1000 多个患者样本的分析中，我们清楚地表明岩藻糖基化糖蛋白可以单独或与其他标记物组合形成敏感且特异的 HCC 标记物。然而，在我们的分析中，我们确定除了核心岩藻糖基化之外，肝脏疾病还会发生许多其他变化。其中一些变化是癌症特异性的，可用于补充我们现有的标记物，而另一些变化可能仅因肝病（炎症）而发生并导致假阳性。因此，在目标 1 中，我们将开发新颖且独特的试剂，这些试剂将显着改进我们的检测方法，并继续我们的发现工作，寻找可在临床上用于 HCC 管理的生物标志物。在目标 2 中，我们将利用新的凝集素并继续我们的发现工作，努力在生物标志物阴性群体中找到新的生物标志物，这些生物标志物可以补充我们现有的标志物，并实现 100% 的敏感性和 100% 的特异性。最后，在目标 3 中，我们将在 NCI 赞助的一项研究中测试我们的主要标志物，该研究包括 350 多例 HCC 病例，并且我们已获得资格预审。在这 5 年结束时，我们将验证我们的生物标志物，并明确证明我们的假设，即岩藻糖基化蛋白可以产生敏感且特异的 HC 标志物。