Serum N-glycan analysis in breast cancer patients - Relation to tumour biology and clinical outcome
Serum N-glycan analysis in breast cancer patients - Relation to tumour biology and clinical outcome
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DOI：
10.1016/j.molonc.2015.08.002
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发表时间：
2016-01-01
影响因子：
6.6
通讯作者：
Yakhini, Zohar
中科院分区：
文献类型：
--
作者：
Haakensen, Vilde D.;Steinfeld, Israel;Yakhini, Zohar
糖基化和相关过程在癌症的发生和发展，包括转移中起重要作用。一些研究表明，N-聚糖作为癌症血清生物标志物具有潜在的诊断价值。我们通过研究104例乳腺癌患者的血清糖组和肿瘤转录组（mRNA和miRNA），探索了特定血清N-聚糖结构丰度作为乳腺肿瘤生物学重要特征的意义。整合这些类型的分子数据使我们能够研究血清聚糖和代表功能途径（如代谢途径或DNA损伤反应）的转录本之间的关系。我们确定血清中的三触角三半乳糖基化三唾液酸化聚糖与参与粘着斑和整合素介导的细胞粘附的肿瘤转录物水平较低相关。这些聚糖结构也与ER阴性肿瘤患者的预后不良有关。高丰度的简单单触角聚糖结构与存活率增加相关，特别是在基底样亚组中。发现循环肿瘤细胞的存在与几种血清糖组结构显著相关，如双触角和三触角、二半乳糖基化和三半乳糖基化、二唾液酸化和三唾液酸化。还检查了肿瘤miRNA表达水平和N-聚糖产生之间的联系。(C)2015年欧洲生物化学学会联合会。Elsevier B. V.出版，保留所有权利。
Glycosylation and related processes play important roles in cancer development and progression, including metastasis. Several studies have shown that N-glycans have potential diagnostic value as cancer serum biomarkers. We have explored the significance of the abundance of particular serum N-glycan structures as important features of breast tumour biology by studying the serum glycome and tumour transcriptome (mRNA and miRNA) of 104 breast cancer patients. Integration of these types of molecular data allows us to study the relationship between serum glycans and transcripts representing functional pathways, such as metabolic pathways or DNA damage response. We identified tri antennary trigalactosylated trisialylated glycans in serum as being associated with lower levels of tumour transcripts involved in focal adhesion and integrin-mediated cell adhesion. These glycan structures were also linked to poor prognosis in patients with ER negative tumours. High abundance of simple monoantennary glycan structures were associated with increased survival, particularly in the basal-like subgroup. The presence of circulating tumour cells was found to be significantly associated with several serum glycome structures like bi and triantennary, di- and trigalactosylated, di- and trisialylated. The link between tumour miRNA expression levels and N-glycan production is also examined. (C) 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.