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 α2,6-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.
Highlights
Altered protein glycosylation is a feature of carcinogenesis, profoundly affecting protein structure and cancer cell behaviour
The initial enzyme-linked immunosorbent assay (ELISA) and enzyme-linked lectin assay (ELLA) analysis indicated that Helix pomatia agglutinin (HPA) bound to immunoglobulin A1 (IgA1) from the breast cancer (BCa) samples to a greater extent than to IgA from normal healthy individuals
The glycosylation of IgA1 from women with metastatic and non-metastatic BCa was compared with IgA1 from normal healthy women
Summary
Altered protein glycosylation is a feature of carcinogenesis, profoundly affecting protein structure (and function) and cancer cell behaviour. The lectin Helix pomatia agglutinin (HPA) recognizes aberrant glycosylation in breast cancer (BCa) [1] and is associated with the propensity of cancer cells to metastasize and with poor patient prognosis [2,3,4,5,6,7]. Studies with serum from BCa patients have identified immunoglobulin A1 (IgA1), complement protein C3, alpha-2-macroglobulin, cadherin V and polyimmunoglobulin receptor ( pIgR) as HPA binding proteins [16,17]. Previous work carried out by our group has identified IgA1 as a significant HPA binding protein in BCa metastases to the liver [18]
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