Comunale Mary Ann, Lowman Melissa, Long Ronald E, Krakover Jonathan, Philip Ramila, Seeholzer Steven, Evans Alison A, Hann Hie-Won L, Block Timothy M, Mehta Anand S
Drexel Institute for Biotechnology and Virology Research, Department of Microbiology and Immunology, Drexel University College of Medicine, Doylestown, Pennsylvania 18901, USA.
J Proteome Res. 2006 Feb;5(2):308-15. doi: 10.1021/pr050328x.
Changes in N-linked glycosylation are known to occur during the development of cancer. For example, increased branching of oligosaccharides has been associated with metastasis and has been correlated to tumor progression in human cancers of the breast, colon and melanomas. Increases in core fucosylation have also been associated with the development of hepatocellular carcinoma (HCC). Chronic infection with the hepatitis B virus is associated with more than 55% of all cases of hepatocellular carcinoma. We show here that increased levels of core fucosylation can be observed via glycan analysis of total serum and are associated with the development of HCC. In a blinded study, the serum glycoproteins derived from people diagnosed with HBV induced liver cancer were found to possess a dramatically higher level of fucosylation. This change occurs on both immunoglobulin molecules and on other serum glycoproteins. Targeted glycoproteomic analysis was used to identify those glycoproteins that are hyperfucosylated in cancer. In total, 19 proteins were found to be hyperfucosylated in cancer. The potential of these proteins as biomarkers of cancer is discussed.
已知在癌症发展过程中会发生N-糖基化变化。例如，寡糖分支增加与转移有关，并且与人类乳腺癌、结肠癌和黑色素瘤的肿瘤进展相关。核心岩藻糖基化增加也与肝细胞癌（HCC）的发展有关。超过55%的肝细胞癌病例与乙型肝炎病毒慢性感染有关。我们在此表明，通过对全血清进行聚糖分析可以观察到核心岩藻糖基化水平升高，并且这与肝细胞癌的发展有关。在一项盲法研究中，发现来自被诊断为乙肝诱导性肝癌患者的血清糖蛋白具有显著更高水平的岩藻糖基化。这种变化发生在免疫球蛋白分子和其他血清糖蛋白上。靶向糖蛋白质组分析用于鉴定癌症中高岩藻糖基化的糖蛋白。总共发现有19种蛋白质在癌症中高岩藻糖基化。还讨论了这些蛋白质作为癌症生物标志物的潜力。
