The α-
fetoprotein fraction L3 (AFP-L3), which is synthesized by malignant cells and incorporates a fucosylated
oligosaccharide, has been investigated as a diagnostic and prognostic marker for
hepatocellular carcinoma (HCC). Quantification of AFP-L3 by conventional
enzyme-linked
immunosorbent assay (ELISA) has not always produced reliable results for serum samples with low AFP, and thus we evaluated the clinical utility of quantifying AFP-L3 using a new and highly sensitive
glycan microarray assay. Sera from 9 patients with
chronic hepatitis B and 32 patients with hepatitis B virus (HBV)-related HCC were tested for AFP-L3 level using the
glycan microarray. Additionally, we compared receiver operator characteristic curves for the ELISA and
glycan microarray methods for determination of the AFP-L3: AFP-L1 ratio in patient samples. This ratio was calculated for 8 HCC patients who underwent transarterial embolization
therapy pre- or post-treatment with AFP-L3.
Glycan microarrays showed that the AFP-L3 ratio of HBV-related HCC patients was significantly higher than that measured for
chronic hepatitis B patients. Overall parameters for estimating AFP-L3% in HCC samples were as follows: sensitivity, 53.13%; specificity, 88.89%; and area under the curve, 0.75. The elevated AFP-L3% in the 8 patients with HBV-related HCC was strongly associated with HCC progression. Following one month of transarterial embolization
therapy, the relative mean AFP-L3% decreased significantly. In addition, we compared Fut8 gene expression between paired
tumor and non-
tumor tissues from 24 patients with HBV-related HCC. The Fut8
mRNA expression was significantly increased in tumorous tissues in these patients than that in non-
tumor tissue controls. Higher expression of Fut8
mRNA in tumorous tissues in these patients was associated with poor differentiation than well and moderate differentiation. Our results describe a new
glycan microarray for the sensitive and rapid quantification of fucosylated AFP; this method is potentially applicable to screening changes in AFP-L3 level for assessment of HCC progression.