Title | Serum IgA1 shows increased levels of α 2,6-linked sialic acid in breast cancer |
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Authors | Lomax-Browne, Hannah J., Robertson, Claire, Antonopoulos, Aristotelis, Leathem, Anthony J. C., Haslam, Stuart M., Dell, Anne and Dwek, M. |
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Abstract | The lectin Helix pomatia agglutinin (HPA) recognizes altered glycosylation in solid cancers and the identification of HPA binding partners in tumour tissue and serum is an important aim. Among the many HPA binding proteins, IgA1 has been reported to be the most abundant in liver metastases. In this study, the glycosylation of IgA1 was evaluated using serum samples from patients with breast cancer (BCa) and the utility of IgA1 glycosylation as a biomarker was assessed. Detailed mass spectrometric structural analysis showed an increase in disialo-biantennary N- linked glycans on IgA1 from BCa patients ( p < 0.0001: non-core fucosylated; p = 0.0345: core fucosylated) and increased asialo-Thomsen–Friedenreich antigen (TF) and disialo-TF antigens in the O- linked glycan preparations from IgA1 of cancer patients compared with healthy control individuals. An increase in Sambucus nigra binding was observed, suggestive of increased α 2,6-linked sialic acid on IgA1 in BCa. Logistic regression analysis showed HPA binding to IgA1 and tumour size to be significant independent predictors of distant metastases ( χ 2 13.359; n = 114; p = 0.020) with positive and negative predictive values of 65.7% and 64.6%, respectively. Immunohistochemical analysis of tumour tissue samples showed IgA1 to be detectable in BCa tissue. This report provides a detailed analysis of serum IgA1 glycosylation in BCa and illustrates the potential utility of IgA1 glycosylation as a biomarker for BCa prognostication. |
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Keywords | Biotechnology |
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| Biophysics |
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| Biochemistry |
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| Bioengineering |
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| Biomaterials |
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| Biomedical Engineering |
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Article number | 20180079 |
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Journal | Interface Focus |
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Journal citation | 9 (2), p. 20180079 |
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ISSN | 2042-8898 |
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| 2042-8901 |
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Year | 2019 |
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Publisher | The Royal Society |
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Digital Object Identifier (DOI) | https://doi.org/10.1098/rsfs.2018.0079 |
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Publication dates |
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Published online | 15 Feb 2019 |
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Published in print | 06 Apr 2019 |
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Project | BBF008309 and BBK016164 |
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| 51808392 |
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Funder | Biotechnology and Biological Sciences Research Council |
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| University of Westminster curates the DietCompLyf database |
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