Liver Cancer and the Role of Protein Hyper-Fucosylation

描述（由申请人提供）：这是一份重新提交的提案，旨在了解与原发性人肝细胞癌（HCC）相关的糖蛋白高度聚焦的性质。与健康人相比，HCC患者的循环中含有丰富的糖蛋白，其n -聚糖核心集中。如果这种修饰与蛋白质功能和/或在疾病中起作用有关，那么为什么这种修饰如此高，我们知之甚少。甚至不确定是否是癌细胞产生了集中的糖型。这种改良的应用程序将系统地确定哪些细胞产生三种“前哨”高度聚焦的糖蛋白，以及聚焦化的功能后果，在与聚焦化和非聚焦化糖型的比较研究中。选择血红素、激肽原和GP73蛋白来代表不同的类别，每一种蛋白都被确定在集中的糖型中与HCC相关。在此过程中，聚焦化在指导肝细胞糖蛋白分选中起作用的重要假设也将得到验证。因此，这项工作的结果旨在回答为什么聚焦化似乎是HCC的共同特征这一基本问题，并有助于开发早期检测和可能的治疗干预措施。公共卫生相关性：通过在诊断为肝癌的人血液中检测到的蛋白质中含有糖、焦糖。了解原因将有助于开发新的诊断方法，并为开发新的治疗方法提供线索。

DESCRIPTION (provided by applicant): This is a re-submission of a proposal to gain an understanding about the nature of the hyper-fucosylation of glycoproteins associated with primary human hepatocellular carcinoma (HCC). Compared to healthy individuals, the circulation of people with HCC contains an abundance of glycoproteins with fucosylation at their N-glycan cores. Little is known about why this modification is so elevated, if it relates to protein function and/or plays a role in disease. There is even uncertainty about whether or not it is the cancer cells that are producing the fucosylated glycoforms. This modified application will systematically determine which cells are producing three "sentinel" hyper-fucosylated glycoproteins, as well as the functional consequences of fucosylation, in comparative studies with fucosylated and unfucosylated glycoforms. The proteins hemopexin, kininogen and GP73, each determined to correlate in the fucosylated glycoform with HCC, are chosen to represent different categories. In doing this, the important hypothesis that fucosylation plays a role in directing the sorting of hepatocytes glycoproteins will also be tested. The results of this work are thus intended to answer the fundamental question as to why fucosylation seems to be a common feature in HCC and help in developing early detection and possibly therapeutic interventions. PUBLIC HEALTH RELEVANCE: By proteins detected in the blood of people with a diagnosis of liver cancer contain the sugar, fucose. Understanding why will help in the development of new diagnostic methods, as well as provide clues for development of new therapies.