Automated immunoassay system for AFP–L3% using on-chip electrokinetic reaction and separation by affinity electrophoresis

Kagebayashi, Chiaki; Yamaguchi, Isao; Akinaga, Ayumi; Kitano, Hiromichi; Yokoyama, Kazunori; Satomura, Masahiro; Kurosawa, Tatsuo; Watanabe, Mitsuo; Kawabata, Tomohisa; Chang, William W.; Li, Chen; Bousse, Luc; Wada, Henry G.; Satomura, Shinji

doi:10.1016/j.ab.2009.02.030

Cited by 119 publications

(121 citation statements)

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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

111

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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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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

111

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“…However, the main advantage of LeMBA, we believe, is as a part of an integrated translational biomarker pipeline leading to lectin immunoassays. The lack of glycan structure details is not critical for clinical translation, as exemplified by the alpha-fetoprotein-L3 (AFP-L3) test, which measures the Lens culinaris agglutinin (LCA) binding fraction of serum alpha-fetoprotein (24,25), and has been approved by the U.S. Food and Drug Administration for detection of hepatocellular carcinoma.…”

mentioning

confidence: 99%

Serum Glycoprotein Biomarker Discovery and Qualification Pipeline Reveals Novel Diagnostic Biomarker Candidates for Esophageal Adenocarcinoma

Shah

Cao

Choi

et al. 2015

Molecular & Cellular Proteomics

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We report an integrated pipeline for efficient serum glycoprotein biomarker candidate discovery and qualification that may be used to facilitate cancer diagnosis and management. The discovery phase used semi-automated lectin magnetic bead array (LeMBA)-coupled tandem mass spectrometry with a dedicated data-housing and analysis pipeline; GlycoSelector (http://glycoselector.di. uq.edu.au). The qualification phase used lectin magnetic bead array-multiple reaction monitoring-mass spectrometry incorporating an interactive web-interface, Shiny mixOmics (http://mixomics-projects.di.uq.edu.au/Shiny), for univariate and multivariate statistical analysis. Relative quantitation was performed by referencing to a spiked-in glycoprotein, chicken ovalbumin. We applied this workflow to identify diagnostic biomarkers for esophageal adenocarcinoma (EAC), a life threatening malignancy with poor prognosis in the advanced setting. EAC develops from metaplastic condition Barrett's esophagus (BE). Currently diagnosis and monitoring of at-risk patients is through endoscopy and biopsy, which is expensive and requires hospital admission. Hence there is a clinical need for a noninvasive diagnostic biomarker of EAC. In total 89 patient samples from healthy controls, and patients with BE or EAC were screened in discovery and qualification stages. Of the 246 glycoforms measured in the qualification stage, 40 glycoforms (as measured by lectin affinity) qualified as candidate serum markers. The top candidate for distinguishing healthy from BE patients' group was Narcissus pseudonarcissus lectin (

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“…The new method uses on-chip electrokinetic reaction and separation by affinity electrophoresis (micro-total (14). In patients with an AFP level of ≥20 µg/ml, µ-TAS AFP-L3% correlated well with LiBASys AFP-L3% (15). Furthermore, this system has enabled the accurate measurement of AFP-L3% at very low AFP concentrations.…”

Section: Introductionmentioning

confidence: 99%

“…For the BLD without HCC group, measurements were made at the time of diagnosis of chronic liver disease. Highly sensitive AFP-L3% (hs-AFP-L3%) were measured by a microchip capillary electrophoresis and liquid-phase binding assay on a µ-TASWako i30 auto analyzer (Wako Pure Chemical Industries, Ltd., Osaka, Japan) (15). Conventional AFP-L3% (c-AFP-L3%) was examined using a column chromatography and liquidphase binding assay on a LiBASys auto analyzer (Wako Pure Chemical Industries, Ltd.) (13).…”

Section: Measurement Of Serum Afp and Afp-l3%mentioning

confidence: 99%

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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Automated immunoassay system for AFP–L3% using on-chip electrokinetic reaction and separation by affinity electrophoresis

Cited by 119 publications

References 21 publications

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

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

Serum Glycoprotein Biomarker Discovery and Qualification Pipeline Reveals Novel Diagnostic Biomarker Candidates for Esophageal Adenocarcinoma

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

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