Breast Cancer Research Group, EGA Institute for Women's Health, University College London, London WC1E 6BT, UK.
Glycobiology. 2011 Aug;21(8):1060-70. doi: 10.1093/glycob/cwr045. Epub 2011 Apr 19.
Altered protein glycosylation compared with the disease-free state is a universal feature of cancer cells. It has long been established that distinct glycan structures are associated with specific forms of cancer, but far less is known about the complete array of glycans associated with certain tumors. The cancer glycome has great potential as a source of biomarkers, but progress in this field has been hindered by a lack of available techniques for the elucidation of disease-associated glycosylation. In the present study, lectin microarrays consisting of 45 lectins with different binding preferences covering N- and O-linked glycans were coupled with evanescent-field activated fluorescent detection in the glycomic analysis of primary breast tumors and the serum and urine of patients with metastatic breast cancer. A single 50 µm section of a primary breast tumor or <1 µL of breast cancer patient serum or urine was sufficient to detect glycosylation alterations associated with metastatic breast cancer, as inferred from lectin-binding patterns. The high-throughput, sensitive and relatively simple nature of the simultaneous analysis of N- and O-linked glycosylation following minimal sample preparation and without the need for protein deglycosylation makes the lectin microarray analysis described a valuable tool for discovery phase glycomic profiling.
与无疾病状态相比，蛋白质糖基化的改变是癌细胞的普遍特征。长期以来，人们已经确定了不同的聚糖结构与特定形式的癌症有关，但对于与某些肿瘤相关的完整聚糖阵列知之甚少。癌症糖组学具有作为生物标志物来源的巨大潜力，但由于缺乏用于阐明与疾病相关的糖基化的可用技术，该领域的进展一直受到阻碍。在本研究中，使用包含 45 种具有不同结合偏好的凝集素的凝集素微阵列，结合瞬逝场激活荧光检测，对原发性乳腺癌以及转移性乳腺癌患者的血清和尿液进行了糖组学分析。从凝集素结合模式推断，只需一个原发性乳腺癌的 50 µm 切片或 <1 µL 的乳腺癌患者血清或尿液，就足以检测与转移性乳腺癌相关的糖基化改变。由于需要最小的样品制备，并且不需要蛋白质糖基化，因此同时分析 N-和 O-连接的糖基化的高通量、灵敏和相对简单的性质使得所描述的凝集素微阵列分析成为发现阶段糖组学分析的有价值的工具。
