Carbohydrate structures of human α-fetoprotein of patients with hepatocellular carcinoma: presence of fucosylated and non-fucosylated triantennary glycans

Abstract

Summary Chemical structures of the sugar chains of various human ax-fetoprotein (AFP) species with different affinity for Concanavalin A (Con A) and Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion. Using reversed-phase and size-fractionation high performance liquid chromatography systems we identified six pyridylamino-sugar chains. The Con A-reactive and LCA-nonreactive species of AFP from patients with hepatocellular carcinoma contained a biantennary sugar chain, and the Con A-reactive and LCA-reactive species had a biantennary one with a fucose residue at the innermost N-acetylglucosamine residue. The Con A-nonreactive and LCA-reactive species contained a biantennary sugar chain both with a bisecting-N-acetylglucosamine residue at the trimannosyl core and with a focuse residue at the innermost N-acetylglucosamine residue. The Con A-nonreactive and LCA-nonreactive species contained a fucosylated triantennary sugar chain as a major component, and two minor components: a triantennary sugar chain and a biantennary sugar chain with a bisecting-N-acetylglucosamine residue at the trimannosyl core. Thus, the fucosylated and non-fucosylated triantennary sugar chains were newly identified in human AFP. Essentially identical results were obtained for AFP from the patient with gallbladder carcinoma which metastasises to the liver. These results indicate that the increment in fucosylation and branching to form new antennae is a characteristic feature of the carbohydrate chains of AFP from patients with neoplastic diseases of the liver.

Isoelectric focusing of alphafetoprotein in patients with hepatocellular carcinoma-frequency of specific banding patterns at non-diagnostic serum levels

“…More attention had been paid to distinguishing between AFP variants based on their lectin-binding characteristics. The biochemical basis for these changes has been described in detail (Yoshima et al, 1980;Yamashita et al, 1983;Krusius and Ruoslahti, 1982;Aoyagi et al, 1993;Tekata, 1990).…”

“…However, by the time a confident diagnosis is arrived at, the tumour may be too large for resection. A more sophisticated approach is to distinguish between the different AFP variants based on their differing carbohydrate moieties (Yoshima et al, 1980;Yamashita et al, 1983;Krusius and Ruoslahti, 1982;Aoyagi et al, 1993;Tekata, 1990). Several groups have reported that AFP originating from HCC and that from chronic liver disease have different lectin-binding capacities (Taketa et al, 1983;Du et al, 1991;Sato et al, 1993).…”

Serum α-Fetoprotein Response as a Surrogate for Clinical Outcome in Patients Receiving Systemic Therapy for Advanced Hepatocellular Carcinoma

“…Normally produced by the fetal yolk sac, liver, and intestine, elevated levels can be associated with HCC in the appropriate clinical setting [11]. Previous studies have documented that the level of AFP at diagnosis may be predictive of patient survival [12][13][14][15].…”

Analysis ofN-glycan in serum glycoproteins fromdb/dbmice and humans with type 2 diabetes

“…Alterations in glycans in cancer cells were shown and linked with cell adhesion, metastasis, and oncogenic transformation, and those in the endothelium of inflammation tissue were shown and linked with leukocyte homing (9). Moreover, the structural changes in the N-glycan of serum proteins are associated with some diseases, e.g., agalactosylation (35) and fucosylation (14) of IgG in rheumatoid arthritis (32) and ␣1,6-fucosylation of ␣-fetoprotein in hepatocellular carcinoma (3,4). Those are suggested to be useful for clinical markers (2).…”