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A targeted glycoproteomic approach identifies cadherin-5 as a novel biomarker of metastatic breast cancer

机译:靶向糖蛋白组学方法将cadherin-5鉴定为转移性乳腺癌的新型生物标志物

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摘要

Aberrant glycosylation has long been recognised as a hallmark of cancer, and is increasingly being exploited in biomarker discovery studies. Helix pomatia agglutinin (HPA) is known to bind aberrant glycans associated with metastatic breast cancer, and was used here to isolate glycoproteins from pooled breast cancer serum samples of (i) patients with recurrent breast cancer and (ii) patients with no sign of recurrence 5. years after diagnosis of their primary tumour. Pregnancy zone protein, the polymeric immunoglobulin receptor and cadherin-5 emerged as potential markers of metastasis following proteomic identification of HPA binding glycoproteins. ELISAs were developed to verify these findings, and to assess protein glycosylation, in individual patient sera. The cadherin-5 ELISA discriminated serum samples of patients with recurrent breast cancer from those with no sign of recurrence, and analysis of cadherin-5 glycosylation by HPA also showed a significant difference between the two sample groups. The targeted glycoproteomic and validatory approach developed here has shown that when taking into account both the protein levels and HPA binding, serum cadherin-5 discriminated patients with recurrent breast cancer from those with no sign of recurrence with 90% specificity.
机译:长期以来,异常糖基化一直被认为是癌症的标志,并且在生物标志物发现研究中越来越多地被利用。螺旋血球凝集素(HPA)已知会结合与转移性乳腺癌相关的异常聚糖,并在此处用于从合并的乳腺癌血清样本中分离糖蛋白,这些血清样本来自(i)复发性乳腺癌患者和(ii)无复发迹象的患者5.诊断出其原发肿瘤后数年。蛋白质组学鉴定HPA结合糖蛋白后,妊娠区蛋白,聚合免疫球蛋白受体和cadherin-5成为转移的潜在标志。开发了ELISA来验证这些发现,并评估单个患者血清中的蛋白质糖基化。 cadherin-5 ELISA可以将复发性乳腺癌患者的血清样品与无复发迹象的患者区别开来,通过HPA对cadherin-5糖基化的分析也显示出两组之间的显着差异。此处开发的靶向糖蛋白组学和验证方法表明,同时考虑蛋白质水平和HPA结合时,血清cadherin-5可以将复发性乳腺癌患者与无复发迹象的患者区别开,具有90%的特异性。

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