Background/aims: Our previous results showed that the percentage of fucosylated species of alpha-fetoprotein (AFP) in total AFP, fucosylation index, was a very useful diagnostic tool to distinguish AFP due to hepatocellular carcinoma from AFP due to non-neoplastic liver diseases. On the other hand, alpha1-6 fucosyl-transferase (alphaFT) catalyzes the addition of fucose from GDP-fucose through an alpha1-6 linkage to the reducing end of N-acetylglucosamine residue of N-linked oligosaccharides of glycoproteins. However, the biological and clinical significance of alphaFT in patients with hepatocellular carcinoma is not fully understood. In the present study, we measured alphaFT activity to elucidate the enzymatic background of fucosylated species of AFP in hepatocellular carcinoma.
Methods: Plasma samples from 84 cases of hepatocellular carcinoma, 40 of liver cirrhosis, 40 of chronic hepatitis and 30 of normal controls, and 26 paired samples of hepatocellular carcinoma and surrounding noncancerous tissues were enrolled in the present study. AlphaFT activity was measured by high performance liquid chromatography with a synthesized fluorescence-labeled glycopeptide with an asialoagalactobiantennary sugar chain as a substrate in the presence of GDP-fucose.
Results: Plasma alphaFT activities (mean+/-SD, pmol/ml/h) in patients with hepatocellular carcinoma, liver cirrhosis, chronic hepatitis and normal controls were 435+/-271, 490+/-290, 590+/-209 and 380+/-133, respectively. AlphaFT levels in hepatocellular carcinoma and chronic liver diseases were increased compared with that in normal controls. A statistically significant positive correlation was observed between plasma alphaFT activity and fucosylation index of AFP (r=0.34, p= 0.0032) in 60 patients with hepatocellular carcinoma, in which increments of serum AFP were observed. When the tentative cutoff value of fucosylation index was set at 18%, which corresponded to the cutoff value to discriminate between hepatocellular carcinoma and non-neoplastic liver diseases in our previous study, the plasma alphaFT activity in hepatocellular carcinoma patients whose fucosylation index was more than 18% (n=32, 523+/-324 pmol/ml/h) was higher than that in hepatocellular carcinoma patients whose fucosylation index was equal to or less than 18% (n=28, 383+/-229) (p=0.055). An increment of the plasma levels of alphaFT occurred in accordance with an advancement of hepatocellular carcinoma stages. Tissue aFT activity in hepatocellular carcinoma (175+/-178 pmol/mg/h) was higher than those in surrounding noncancerous liver (144+/-134) and in normal liver (79+/-19). The mean alphaFT activities in well-, moderately- and poorly-differentiated hepatocellular carcinoma were 38+/-0.7, 177+/-182 and 219+/-189, respectively, and they tended to increase with dedifferentiation in hepatocellular carcinoma tissues.
Conclusions: The present study indicates that alphaFT is responsible for the formation of the fucosylated species of AFP in hepatocellular carcinoma and suggests that the measurement of alphaFT provides a possible aid in the evaluation of the degree of advancement in patients with hepatocellular carcinoma.