Abstract
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.
Highlights
Hepatocellular carcinoma (HCC) is the sixth most common malignancy and the third most common cause of cancer-related death worldwide [1], and a large proportion of cases are diagnosed as advanced-stage HCC [2]
We first investigated the clinical utility of a-fetoprotein fraction L3 (AFP-L3) via a newly developed and highly sensitive method using serum samples from patients with chronic hepatitis B (CHB) and HCC
It is well known that AFP-L3 concentration correlates well with AFP; AFP-L3% is not correlated with AFP [25,26]
Summary
Hepatocellular carcinoma (HCC) is the sixth most common malignancy and the third most common cause of cancer-related death worldwide [1], and a large proportion of cases are diagnosed as advanced-stage HCC [2]. Recent advances in dynamic imaging techniques, including computed tomography and magnetic resonance imaging, have facilitated the detection of small and early-stage HCC [7,8,9], the relative high cost and risks associated with these techniques limit their use. Because patients with advanced HCC generally have a poor prognosis, detection of early-stage HCC is the best strategy to improve outcomes [10,11]. In this regard, there is urgent need to identify more sensitive and reliable serum biomarkers for detection of HCC
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