Identification and Development of Fucosylated Glycoproteins as Biomarkers of Primary Hepatocellular Carcinoma

Changes in N-linked glycosylation are known to occur during the development of cancer. For example, we have previously reported changes in N-linked glycosylation that occur with the development of hepatocellular carcinoma (HCC) and, through the use of glycoproteomics, identified many of those proteins containing altered glycan structures. To advance these studies and further explore the glycoproteome, we performed N-linked glycan analysis from serum samples depleted of the major acute phase proteins, followed by targeted lectin extraction of those proteins containing changes in glycosylation. Using this method, changes in glycosylation, specifically increased amounts of core and outer arm fucosylation, were observed in the depleted samples. The identities of those proteins containing core and outer arm fucose were identified in the serum of patients with HCC. The usefulness of some of these proteins in the diagnosis of HCC was determined through the analysis of over 300 patient samples using a high-throughput plate based approach. Greatest performance was achieved with fucosylated hemopexin, which had an AUROC of 0.9515 with an optimal sensitivity of 92% and a specificity of 92%.