Primary Breast Cancer Tumours Contain High Amounts of IgA1 Immunoglobulin: An Immunohistochemical Analysis of a Possible Carrier of the Tumour-Associated Tn Antigen

Welinder, Charlotte; Baldetorp, Bo; Blixt, Ola; Grabau, Dorthe; Jansson, Bo

doi:10.1371/journal.pone.0061749

Cited by 30 publications

(30 citation statements)

References 31 publications

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“…FFPE primary BCa specimens were probed with sheep polyclonal anti-IgA1 and, in common with the recent report by Welinder et al [41], all the samples showed reactivity with the antibody, confirming the presence of IgA1 in these tissues (figure 1). Protein preparations from the same tumour tissues were separated by SDS-PAGE and western blotted and probed with the same anti-IgA1 antibody, verifying the findings of the immunochemistry (figure 1).…”

Section: Iga1 Breast Tissue Immunochemistry and Protein Separationsupporting

confidence: 83%

Serum IgA1 shows increased levels ofα2,6-linked sialic acid in breast cancer

et al. 2019

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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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Section: Iga1 Breast Tissue Immunochemistry and Protein Separationsupporting

confidence: 83%

Serum IgA1 shows increased levels ofα2,6-linked sialic acid in breast cancer

et al. 2019

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“…To our best knowledge, anomalies of IgA N-glycopeptides have not yet been described in sera of cancer patients, although aberrantly O-glycosylated IgA carrying the Tn antigen was recently described in breast tumor tissue. 24 …”

Section: Discussionmentioning

confidence: 99%

Protein-Specific Differential Glycosylation of Immunoglobulins in Serum of Ovarian Cancer Patients

et al. 2016

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Previous studies indicated that glycans in serum may serve as biomarkers for diagnosis of ovarian cancer; however, it was unclear to which proteins these glycans belong. We hypothesize that protein-specific glycosylation profiles of the glycans may be more informative of ovarian cancer and can provide insight into biological mechanisms underlying glycan aberration in serum of diseased individuals. Serum samples from women diagnosed with epithelial ovarian cancer (EOC, n = 84) and matched healthy controls (n = 84) were obtained from the Gynecologic Oncology Group. Immunoglobulin (IgG, IgA, and IgM) concentrations and glycosylation profiles were quantified using multiple reaction monitoring mass spectrometry. Differential and classification analyses were performed to identify aberrant protein-specific glycopeptides using a training set. All findings were validated in an independent test set. Multiple glycopeptides from immunoglubins IgA, IgG, and IgM were found to be differentially expressed in serum of EOC patients compared with controls. The protein-specific glycosylation profiles showed their potential in the diagnosis of EOC. In particular, IgG-specific glycosylation profiles are the most powerful in discriminating between EOC case and controls. Additional studies of protein- and site-specific glycosylation profiles of immunoglobulins and other proteins will allow further elaboration on the characteristics of biological functionality and causality of the differential glycosylation in ovarian cancer and thus ultimately lead to increased sensitivity and specificity of diagnosis.

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“…In contrast, Tn antigen has little or no expression in normal adult tissues. In many types of cancers, including lung adenocarcinomas , cervical cancer , colorectal carcinomas , gastric carcinomas , and breast carcinomas , the expression of Tn antigen is correlated with metastatic potential and poor prognosis. The role of Tn antigen in the development of cancer remains unclear.…”

Section: Relationship Between Tn Antigen and Tumor Cellsmentioning

confidence: 99%

Tumor‐associated antigens: Tn antigen, sTn antigen, and T antigen

Zhao

Wang

et al. 2016

HLA

159

148

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Glycosylation is one of the major posttranslational modifications of proteins. N-glycosylation (Asn-linked) and O-glycosylation (Ser/Thr-linked) are the two main forms. Abnormal O-glycosylation is frequently observed on the surface of tumor cells, and is associated with an adverse outcome and poor prognosis in patients with cancer. O-glycans (Tn, sTn, and T antigen) can be synthesized in the Golgi apparatus with the aid of several glycosyltransferases (such as T-synthase and ST6GalNAc-I) in a suitable environment. The unique molecular chaperone of T-synthase is Cosmc, which helps T-synthase to fold correctly in the endoplasmic reticulum. Dysregulation of these glycosyltransferases, molecular chaperones, or the environment is involved in the dysregulation of O-glycans. Tn, sTn, and T antigen neo- or over-expression occurs in many types of cancer including gastric, colon, breast, lung, esophageal, prostate, and endometrial cancer. This review discusses the major synthetic pathway of O-glycans and the mechanism by which Tn, sTn, and T antigens promote tumor metastasis.

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Primary Breast Cancer Tumours Contain High Amounts of IgA1 Immunoglobulin: An Immunohistochemical Analysis of a Possible Carrier of the Tumour-Associated Tn Antigen

Cited by 30 publications

References 31 publications

Serum IgA1 shows increased levels ofα2,6-linked sialic acid in breast cancer

Serum IgA1 shows increased levels ofα2,6-linked sialic acid in breast cancer

Protein-Specific Differential Glycosylation of Immunoglobulins in Serum of Ovarian Cancer Patients

Tumor‐associated antigens: Tn antigen, sTn antigen, and T antigen

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