Predicting HCC through Glycomics

通过糖组学预测 HCC

• 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
• 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

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）：原始授权的假设是岩藻糖基化随着肝细胞癌（HCC）的发展而增加，岩藻糖基化糖蛋白将成为HCC的敏感和特异性标志物。这一假设已经得到证实，在我们对1000多个患者样本的分析中，我们已经清楚地表明岩藻糖基化糖蛋白可以单独或与其他标志物组合成为HCC的敏感和特异性标志物。然而，在我们的分析中，我们已经确定，除了核心岩藻糖基化之外，还有许多其他变化与肝脏疾病一起发生。其中一些变化是癌症特异性的，可用于补充我们现有的标志物，而另一些变化可能仅发生在肝脏疾病（炎症）中，并导致假阳性。因此，在目标1中，我们将开发新的和独特的试剂，这将大大改善我们的测定，并继续我们的发现努力，以找到可用于临床管理HCC的生物标志物。在目标2中，我们将利用我们的新凝集素并继续我们的发现努力，以在生物标志物阴性人群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，并导致100%的灵敏度和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，该研究包括超过350例HCC病例，我们预先获得了资格。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成为HC的敏感和特异性标志物。