Comparison of carbohydrate structures of serum α-fetoprotein by sequential glycosidase digestion and lectin affinity electrophoresis

Shimizu, Kayoko; Katoh, Hideo; Yamashita, F; Tanaka, Masatoshi; Tanikawa, Kyuichi; Taketa, Kazuhisa; Satomura, Shinji; Matsuura, Shuji

doi:10.1016/0009-8981(96)06369-3

Cited by 47 publications

(40 citation statements)

References 22 publications

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“…A higher abundance of G7 in HCC AFP suggests that fucosylation of AFP is more pronounced in HCC. In support of this conclusion is the finding that lentil lectin-reactive AFP -a proposed diagnostic marker for HCC and not for benign liver disease -appears to be those AFP glycoforms carrying fucosylated N-glycans (Du et al, 1991;Taketa et al, 1993;Shimizu et al, 1996).…”

Section: Discussionsupporting

confidence: 54%

“…However, the present study is the first to provide direct information of the glycan composition of serum AFP. Previously, it has been considered that AFP carries only a single bi-antennary complex-type N-glycan, varying in the degree of sialylation, galactosylation and fucosylation (Yoshima et al, 1980;Yamashita et al, 1993;Shimizu et al, 1996). We have now demonstrated that AFP can also carry O-linked glycans.…”

Section: Discussionmentioning

confidence: 68%

“…Seven N-linked glycans found in this study were composed of the typical GlcNAc 2 Man 3 GlcNAc 2 N-linked heptasaccharide core, with different degrees of sialylation, fucosylation and galactosylation. The G10 (asialo monogalacto) glycan and G11 (asialo agalacto) glycan are two sugar chains of AFP not previously reported, although the presence of serum AFP isoforms with different degrees of galactosylation has been suggested indirectly by a study using sequential exoglycosi- dase digestion and lectin affinity electrophoresis (Shimizu et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

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Glycan composition of serum alpha-fetoprotein in patients with hepatocellular carcinoma and non-seminomatous germ cell tumour

et al. 1999

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Although estimation of serum alpha-fetoprotein (AFP) is widely used in the diagnosis of hepatocellular carcinoma (HCC) and non-seminomatous germ cell tumours (NSGCT), the clinical usefulness of this test is limited by a low specificity. However, there exist glycoforms of AFP which may be more specific for particular tumours. Previously, detailed analysis has been prevented by the low levels of AFP in human serum. We report here the application of fluorescence labelling, sequential exoglycosidase digestion, high-performance liquid chromatography and matrix-assisted laser desorption ionization in time-of-flight mass spectrometry, to determine the glycan structures of purified serum AFP from patients with HCC and NSGCT. Eleven major glycans were found, of which seven were N -linked, and four were O -linked, to the protein backbone. The structure of the N -linked glycans (all of bi-antennary complex-type with varying degrees of sialylation, fucosylation and galactosylation) were consistent with those previously reported. The O -linked glycans (three mucin O -GalNAc type glycans with variable degrees of sialylation, one O -HexNAc monosaccharide glycan) have not previously been reported. The finding of mucin O -GalNAc type glycans was supported by the prediction of potential O -GalNAc glycosylation sites on the protein backbone by analysis of the AFP structure by molecular modelling. With knowledge of these structures it may be possible to develop more specific assays for the detection of HCC and NSGCT. © 1999 Cancer Research Campaign © 1999 Cancer Research Campaign

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Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 68%

Section: Discussionmentioning

confidence: 99%

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Glycan composition of serum alpha-fetoprotein in patients with hepatocellular carcinoma and non-seminomatous germ cell tumour

et al. 1999

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“…The first quantitative serum assays for AFP were established by Ruoshlati and Seppala 18 . Up to 11 AFP isoforms exist based on variations in the glycan terminal chain 19,20 More recently, isoelectric focusing has been investigated, which fractionates AFP into four variant bands, I-IV. AFP bands III and IV can be specific for HCC and help differentiate from AFP of cirrhosis or pregnancy 21 .…”

Section: Resultsmentioning

confidence: 99%

Estimation of serum Alpha feto-protein (AFP), interlukin-6 and Des-?-carboxyprothrombin (DCP) in case of hepatocellular carcinoma

Haque

Ali

Kumar

et al. 2016

Bangladesh J Med Sci

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Abstract:Background: Hepatocellular carcinoma (HCC) is one the most common primary malignancy of the liver and represents the third leading cause of cancer-related deaths worldwide. Incidence rates are highest in East Asia and Sub-Saharan Africa. A number of evidence suggests a possible role of interleukin-6 (IL-6), α-Fetoprotein (AFP) and Des-γ-carboxyprothrombin (DCP) in the pathogenesis of hepatocellular carcinoma (HCC). The high DCP may be related to increase tumour behaviour, such as the presence of vascular invasion and intrahepatic metastasis of HCC cells. Patients and methods: We studied IL-6, AFP and DCP in patients with HCC or in healthy controls. AFP was measured by chemiluminescent immunoassay; Serum IL-6 and DCP were measured by enzyme linked immunosorbent assay in 30 patients with primary hepatocellular carcinoma and 30 normal subjects. Results: IL-6, AFP and DCP were found high in the serum of patients initially diagnosed with HCC (18±9.8), (315.99±594.62) and (26.15±5.01) respectively compared with healthy subjects (4.29±2.10), (3.13±1.27) and (4.25±1.22). A significant positive correlation was found between mean levels of IL-6 & AFP in HCC (P < 0.05), Combination of IL-6, AFP and DCP improved the sensitivity in diagnosing HCC or predicting future HCC development. Conclusions: IL-6, DCP along with AFP could be considered a promising tumor marker for HCC. DCP is a well recognized tumor marker for the screening and diagnosis of HCC. In particular, the diagnostic value of the test is significantly increased when combined with AFP.

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“…To increase the specificity of AFP, the AFP-L3 glycoform can be used as a measure of cancerous changes in the AFP composite carbohydrate moiety. The most frequently used cut-off value is 10% [1], which gives a positive rate of 0/71 (0.0%), 1/90 (1.1%), 0/13 (0.0%), 0/14 (0.0%), and 18/82 (22.0%) for chronic hepatitis, hepatic cirrhosis, dysplastic nodules, early hepatocellular carcinoma, and advanced hepatocellular carcinoma, respectively. This yields a sensitivity of 18.8% and a specificity of 99.4%.…”

mentioning

confidence: 99%

Alpha-fetoprotein-L3: Useful or Useless for Hepatocellular Carcinoma?

2013

Liver Cancer

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Comparison of carbohydrate structures of serum α-fetoprotein by sequential glycosidase digestion and lectin affinity electrophoresis

Cited by 47 publications

References 22 publications

Glycan composition of serum alpha-fetoprotein in patients with hepatocellular carcinoma and non-seminomatous germ cell tumour

Glycan composition of serum alpha-fetoprotein in patients with hepatocellular carcinoma and non-seminomatous germ cell tumour

Estimation of serum Alpha feto-protein (AFP), interlukin-6 and Des-?-carboxyprothrombin (DCP) in case of hepatocellular carcinoma

Alpha-fetoprotein-L3: Useful or Useless for Hepatocellular Carcinoma?

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