NIBRT Dublin-Oxford Glycobiology Laboratory, The National Institute for Bioprocessing Research and Training, Conway Institute, University College Dublin, Belfield, Dublin, Ireland.
Departments of Hematopathology.
Ann Oncol. 2011 May;22(5):1113-1119. doi: 10.1093/annonc/mdq570. Epub 2010 Dec 1.
Metastatic breast cancer (MBC) is currently an incurable condition that is primarily treated with palliative measures. Isolation of circulating tumor cells (CTCs) from the peripheral blood of these patients provides a predictive prognostic indicator, independent of the type of therapy, site of occurrence and biological characteristics of the primary disease. It has been well established that glycosylation processing pathways are disturbed in cancer, leading to alterations in the glycan content of glycoproteins.
The bi-, tri- and tetraantennary glycans containing sialyl Lewis x (sLe(x)) epitopes (A2F1G1, A3F1G1, A4F1G1 and A4F2G2) were quantified using normal phase high-performance liquid chromatography in combination with exoglycosidase array digestions in the glycan pools released from sera of 27 patients with advanced breast cancer (16 with CTCs <5/7.5 ml and 11 with CTCs ≥5/7.5 ml) and 13 healthy women.
The levels of all these glycans were significantly higher in patients with CTCs ≥5/7.5 ml compared with patients with CTCs <5/7.5 ml.
As high levels of glycans containing sLe(x) epitopes were associated with CTCs, their measurement may provide a new noninvasive approach for determining prognosis in women with MBC.
转移性乳腺癌(MBC)目前是一种无法治愈的疾病,主要采用姑息性治疗。从这些患者的外周血中分离循环肿瘤细胞(CTC)可提供一种预测预后指标,与治疗类型、发生部位和原发性疾病的生物学特征无关。已经证实,癌症中糖基化途径受到干扰,导致糖蛋白中聚糖含量发生改变。
使用正相高效液相色谱法结合外切糖苷酶阵列消化,对来自 27 名晚期乳腺癌患者(16 名 CTCs<5/7.5ml 和 11 名 CTCs≥5/7.5ml)和 13 名健康女性血清中释放的聚糖池中含唾液酸化路易斯 x(sLe(x))表位的双、三、四天线聚糖(A2F1G1、A3F1G1、A4F1G1 和 A4F2G2)进行定量分析。
CTC≥5/7.5ml 的患者中所有这些聚糖的水平均明显高于 CTC<5/7.5ml 的患者。
由于含有 sLe(x)表位的聚糖水平与 CTCs 相关,因此其测量可能为确定 MBC 女性患者预后提供一种新的非侵入性方法。