Lomax-Browne Hannah J, Robertson Claire, Antonopoulos Aristotelis, Leathem Anthony J C, Haslam Stuart M, Dell Anne, Dwek Miriam V
School of Life Sciences, University of Westminster, 115 New Cavendish Street, London W1W 6UW, UK.
Department of Life Sciences, Imperial College London, South Kensington Campus, London SW7 2AZ, UK.
Interface Focus. 2019 Apr 6;9(2):20180079. doi: 10.1098/rsfs.2018.0079. Epub 2019 Feb 15.
The lectin 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 linked glycans on IgA1 from BCa patients ( < 0.0001: non-core fucosylated; = 0.0345: core fucosylated) and increased asialo-Thomsen-Friedenreich antigen (TF) and disialo-TF antigens in the linked glycan preparations from IgA1 of cancer patients compared with healthy control individuals. An increase in binding was observed, suggestive of increased 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 ( 13.359; = 114; = 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.
凝集素（HPA）可识别实体癌中糖基化的改变，在肿瘤组织和血清中鉴定HPA结合伴侣是一个重要目标。在众多HPA结合蛋白中，据报道IgA1在肝转移中最为丰富。在本研究中，使用乳腺癌（BCa）患者的血清样本评估了IgA1的糖基化，并评估了IgA1糖基化作为生物标志物的效用。详细的质谱结构分析表明，BCa患者IgA1上的二唾液酸-双天线连接聚糖增加（<0.0001：非核心岩藻糖基化；=0.0345：核心岩藻糖基化），与健康对照个体相比，癌症患者IgA1连接聚糖制剂中的去唾液酸-汤姆森-弗里德赖希抗原（TF）和二唾液酸-TF抗原增加。观察到结合增加，提示BCa中IgA1上2,6-连接唾液酸增加。逻辑回归分析显示，HPA与IgA1的结合以及肿瘤大小是远处转移的重要独立预测因子（=13.359；=114；=0.020），阳性和阴性预测值分别为65.7%和64.6%。肿瘤组织样本的免疫组织化学分析显示，BCa组织中可检测到IgA1。本报告对BCa患者血清IgA1糖基化进行了详细分析，并说明了IgA1糖基化作为BCa预后生物标志物的潜在效用。
