Highly enhanced fucosylation of serum glycoproteins in patients with hepatocellular carcinoma

Abstract

Background: We recently reported that the measurement of Lens culinaris agglutinin-reactive species of alpha-fetoprotein (AFP), alpha-1-antitrypsin (AAT) and transferrin (TF) is useful for the diagnosis of hepatocellular carcinoma (HCC) and that the molecular basis for this reactivity is fucosylation at the innermost N-acetylglucosamine residue of a biantennary sugar chain. However, the precise relationship of the fucosylation of AFP, AAT and TF in patients with HCC and liver cirrhosis is not fully understood. The aim of this study is to delineate the relationship of the fucosylation between these three glycoproteins in HCC.

Methods: Three hundred and thirty-four patients with HCC were referred to our university hospital from 1987 to 1997. An increase in serum AFP (> 20 ng/mL) was observed in 233 (69.8%) patients with HCC. From these 233 patients with AFP-producing HCC, 60 serum samples were randomly selected and used in the present study. As a reference, samples from 60 patients with liver cirrhosis, in which 30 had increased AFP, were used. Lens culinaris agglutinin (LCA)-reactive species were determined by crossed immunoaffinoelectrophoresis (CIAE). The contents of the fucosylated biantennary chain of purified AAT and TF samples were determined as pyridylamino derivatives of each oligosaccharide with high-performance liquid chromatography (HPLC).

Results: There was a highly significant correlation between LCA-reactive species by CIAE and pyridyl-amino-fucosylated biantennary sugar chain by HPLC in both AAT and TF. Lens culinaris agglutinin-reactive species of AFP, AAT and TF in HCC were significantly higher than those in liver cirrhosis. A highly statistically significant positive correlation of fucosylated glycans was observed between AAT and TF in both HCC and liver cirrhosis, but not between AFP and AAT or between AFP and TF. Accordingly, the present results indicate that highly enhanced fucosylation of serum glycoproteins was found in HCC compared with liver cirrhosis and that the combination of measurements of fucosylated AFP with AAT or TF were useful for the diagnosis of HCC.