Identification of Altered Glycan and Glycoproteins in Viral Induced Liver Cancer

描述（由申请人提供）：最初拨款的假设是，随着肝细胞癌（HCC）的发展，聚焦化会增加，并且聚焦化的糖蛋白将成为HCC的敏感和特异性标记物。这一假设已经得到证实，在我们对1000多例患者样本的分析中，我们已经清楚地表明，集中的糖蛋白可以单独或与其他标记物联合制造敏感和特异性的HCC标记物。然而，在我们的分析中，我们已经确定，除了核心聚焦外，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，可以用来补充我们现有的标志物，而其他变化可能只发生在肝脏疾病（炎症）上，并导致假阳性。因此，在目标1中，我们将开发新颖独特的试剂，这将极大地改善我们的检测方法，并继续我们的发现努力，寻找可用于HCC临床管理的生物标志物。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工作，努力在生物标志物阴性人群中找到新的生物标志物，以补充我们现有的标志物，并实现100%的灵敏度和100%的特异性。最后，在目标3中，我们将在一项NCI赞助的研究中测试我们的先导标志物，该研究包括350多例HCC，我们对其进行了预审。在这5年期间结束时，我们将验证我们的生物标志物，并明确证明我们的假设，即聚焦蛋白可以制造敏感和特异性的HC标志物。

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.