Clinical Advantage of Highly Sensitive On-Chip Immunoassay for Fucosylated Fraction of Alpha-Fetoprotein in Patients with Hepatocellular Carcinoma

Tamura, Yasushi; Igarashi, Masato; Kawai, Hirokazu; Suda, Takafumi; Satomura, Shinji; Aoyagi, Yoshinobu

doi:10.1007/s10620-010-1222-5

Cited by 46 publications

(46 citation statements)

References 20 publications

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“…4). Recent investigations have shown that diagnostic sensitivity of hs-AFP-L3% at a cut-off level of 5 or 7% was 41.5 or 41.1%, respectively, in HCC patients with serum AFP <20 ng/ml (18,22). Therefore, our findings in this study support the specificity of hs-AFP-L3% in patients with serum AFP <20 ng/ml, as previously reported.…”

Section: Discussionsupporting

confidence: 90%

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Highly sensitive lens culinaris agglutinin-reactive α-fetoprotein is useful for early detection of hepatocellular carcinoma in patients with chronic liver disease

Ido

2011

Oncol Rep

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Abstract. The fucosylated fraction of α-fetoprotein (AFP-L3) is a specific marker for hepatocellular carcinoma (HCC). However, conventional AFP-L3% (c-AFP-L3%) has not always been reliable in cases with low serum α-fetoprotein (AFP) levels. In this study, we evaluated the clinical utility of a newly developed assay, highly sensitive AFP-L3% (hs-AFP-L3%). Subjects included 74 patients with benign liver disease (BLD), including chronic hepatitis and cirrhosis, and 94 with HCC. Serum hs-AFP-L3% was significantly higher than c-AFP-L3% in patients with early-stage HCC (solitary or <20 mm in diameter). Additionally, hs-AFP-L3% was significantly increased in patients with well-differentiated HCC. In patients with serum AFP <20 ng/ml, the sensitivities of c-AFP-L3% and hs-AFP-L3% were 12.5 and 44.6%, respectively, at a cut-off value of 5%. In 59 BLD patients with serum AFP <20 ng/ml, the HCC-positive rate in patients with hs-AFP-L3% ≥5% was significantly higher compared to those with hs-AFP-L3% <5% during the follow-up period (median, 35 months; range, 5-48 months). Importantly, none of the BLD patients with both serum AFP <20 ng/ml and hs-AFP-L3% <5% developed HCC. These results indicated that hs-AFP-L3% is useful for early detection of HCC in BLD patients, even for those with serum AFP <20 ng/ml. Furthermore, since hs-AFP-L3% increases before HCC is detectable by various advanced imaging modalities, this assay may help identify BLD patients with a higher risk of HCC. IntroductionHepatocellular carcinoma (HCC) is the sixth most common cancer in the world, and the third most common cause of cancer-related death (1). Although it is more common in Asia and Africa, its incidence in the United States has increased over the past two decades, largely due to the spread of hepatitis C (HCV) infection, which is an underlying risk factor (2). Early detection of HCC increases the potential for curative treatment and improves prognosis. Several methods developed for the diagnosis of HCC, including evaluation of serum markers, ultrasonography (US), computed tomography (CT) and magnetic resonance imaging (MRI), have been tested clinically. α-fetoprotein (AFP) and des-γ carboxy prothrombin (DCP), serum proteins that are elevated in HCC, are the most widely used markers. Although routine screening offers the best chance for early tumor detection, the reported sensitivities and specificities of elevated serum AFP and DCP levels vary significantly (3-8). Furthermore, serum AFP levels increase in only 30-40% of patients with HCC, especially early in the disease process (5). Additionally, an increase in serum AFP is also seen in patients with non-cancerous conditions, including cirrhosis or exacerbation of chronic hepatitis (9). AFP-L3, the lectin lens culinaris agglutinin-bound fraction, is one of the three glycoforms of AFP, and is the major glycoform elevated in the serum of HCC patients. The reported sensitivities of AFP-L3 as a method of detecting HCC range from 75-97% with specificities of 90-92% (10,11). In cases of HCC, however, h...

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Section: Discussionsupporting

confidence: 90%

“…2). Since hs-AFP-L3% is reliable even when serum AFP is <20 ng/ml, it is possible to set the cut-off value for hs-AFP-L3% at 5-7% (18,22,23). We show here that at a cut-off level of 5%, the sensitivity and specificity of hs-AFP-L3% were 44.6 and 71.2%, respectively, in HCC patients with serum AFP <20 ng/ml (Fig.…”

Section: Discussionmentioning

confidence: 62%

Highly sensitive lens culinaris agglutinin-reactive α-fetoprotein is useful for early detection of hepatocellular carcinoma in patients with chronic liver disease

Ido

2011

Oncol Rep

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“…Therefore, AFP-L3 has been recognized as a specific marker for HCC. Furthermore, analysis using this marker could be useful for monitoring treatment responses and disease recurrence and could also be a tool for recognition of HCC earlier than that possible by using imaging modalities (34,(37)(38)(39)(40)(41)(42). In recent years, in addition to AFP, new biomarkers possessing fucosides have been discovered.…”

Section: Discussionmentioning

confidence: 99%

A Novel Core Fucose-specific Lectin from the Mushroom Pholiota squarrosa

Kobayashi

Tateno

Dohra

et al. 2012

Journal of Biological Chemistry

108

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Background: Fuc-␣1-6 oligosaccharide has a variety of biological functions. Results: Purification of a novel Fuc␣ 1-6-specific lectin from the mushroom Pholiota squarrosa. Conclusion: The lectin binds only to core ␣1-6-fucosylated N-glycans and not to the other types of fucosylated oligosaccharides. Significance: The lectin will be a promising tool for analyzing the biological functions of ␣1-6 fucosylation.

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“…However, an early increase in AFP levels correlates with poorer outcome with shorter OS and PFS [74] . Japanese groups proposed the lens culinaris agglutinin reactive AFP (AFP-L3), an isoform of AFP, as a good diagnostic and prognostic biomarker for HCC [75][76][77] . However, scant data is/are available regarding the value of AFP-L3 as predictive of response to antiangiogenic agents in HCC [78] .…”

Section: Poorer Prognosismentioning

confidence: 99%

Evaluation of antiangiogenic efficacy in advanced hepatocellular carcinoma: Biomarkers and functional imaging

Bouattour

Payancé

Wassermann

2015

WJH

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Many years after therapeutic wilderness, sorafenib finally showed a clinical benefit in patients with advanced hepatocellular carcinoma. After the primary general enthusiasm worldwide, some disappointments emerged particularly since no new treatment could exceed or at least match sorafenib in this setting. Without these new drugs, research focused on optimi zing care of patients treated with sorafenib. One challenging research approach deals with identifying prognostic and predictive biomarkers of sorafenib in this population. The task still seems difficult; however appropriate investigations could resolve this dilemma, as observed for some malignancies where other drugs were used.

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Clinical Advantage of Highly Sensitive On-Chip Immunoassay for Fucosylated Fraction of Alpha-Fetoprotein in Patients with Hepatocellular Carcinoma

Abstract: μ-TAS AFP-L3 is more sensitive for discriminating HCC than the conventional LiBASys AFP-L3, particularly in subgroups with lower AFP concentrations and early-stage HCC.

Cited by 46 publications

References 20 publications

Highly sensitive lens culinaris agglutinin-reactive α-fetoprotein is useful for early detection of hepatocellular carcinoma in patients with chronic liver disease

Highly sensitive lens culinaris agglutinin-reactive α-fetoprotein is useful for early detection of hepatocellular carcinoma in patients with chronic liver disease

A Novel Core Fucose-specific Lectin from the Mushroom Pholiota squarrosa

Evaluation of antiangiogenic efficacy in advanced hepatocellular carcinoma: Biomarkers and functional imaging

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