Autoantibodies to aberrantly glycosylated MUC1 in early stage breast cancer are associated with a better prognosis.
Autoantibodies to aberrantly glycosylated MUC1 in early stage breast cancer are associated with a better prognosis.
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DOI：
10.1186/bcr2841
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发表时间：
2011-03-08
期刊：
影响因子：
--
通讯作者：
Burchell JM
中科院分区：
文献类型：
--
作者：
Blixt O;Bueti D;Burford B;Allen D;Julien S;Hollingsworth M;Gammerman A;Fentiman I;Taylor-Papadimitriou J;Burchell JM
乳腺癌早期诊断的血清生物标志物的检测仍然是一个重要的目标。O-连接聚糖结构的变化发生在所有乳腺癌中，导致抗原性不同的糖蛋白表达。实际上，广泛用于监测乳腺癌（CA 15.3）疾病进展的血清测定检测糖蛋白（MUC 1），但在早期患者中不能检测到抗原水平的升高。然而，由于免疫系统的作用是放大抗原信号，因此抗体可以在抗原之前很久就在血清中被检测到。我们利用O-糖基化的变化来测量早期乳腺癌患者血清中对癌症相关糖型MUC 1的自身抗体应答。我们使用了60聚体MUC 1糖肽的微阵列平台，以确认一定比例的早期乳腺癌患者（54/198）中存在针对MUC 1的癌症相关糖型的自身抗体。选择5份阳性血清，使用芯片糖基化技术和一组基于在特定位点携带特定聚糖的单个MUC 1串联重复序列的糖肽详细定义反应性表位。基于这些结果，合成更大量的确定的MUC 1糖肽的扩展库，打印在微阵列上，并用来自乳腺癌患者（n = 395）、良性乳腺疾病患者（n = 108）和健康对照（n = 99）的大队列的血清进行筛选。所有的血清都是在20世纪70年代和80年代收集的，并且可以对乳腺癌患者进行完整的临床随访。与对照组相比，癌症患者血清中自身抗体的存在和水平显著较高，并且观察到与年龄的高度显著相关性。核心3 MUC 1（GlcNAcβ1- 3GalNAc-MUC 1）和STnMUC 1（NeuAcα2，6 GalNAc-MUC 1）糖型自身抗体亚组的高水平与发生率降低和转移时间延长显著相关。与良性乳腺疾病或健康女性相比，在早期乳腺癌患者中更频繁地发现特异性癌症相关MUC 1糖型的自身抗体，并且其水平更高。强抗体应答与转移率降低和延迟的相关性表明自身抗体可影响疾病进展。
Detection of serum biomarkers for early diagnosis of breast cancer remains an important goal. Changes in the structure of O-linked glycans occur in all breast cancers resulting in the expression of glycoproteins that are antigenically distinct. Indeed, the serum assay widely used for monitoring disease progression in breast cancer (CA15.3), detects a glycoprotein (MUC1), but elevated levels of the antigen cannot be detected in early stage patients. However, since the immune system acts to amplify the antigenic signal, antibodies can be detected in sera long before the antigen. We have exploited the change in O-glycosylation to measure autoantibody responses to cancer-associated glycoforms of MUC1 in sera from early stage breast cancer patients. We used a microarray platform of 60mer MUC1 glycopeptides, to confirm the presence of autoantibodies to cancer associated glycoforms of MUC1 in a proportion of early breast cancer patients (54/198). Five positive sera were selected for detailed definition of the reactive epitopes using on chip glycosylation technology and a panel of glycopeptides based on a single MUC1 tandem repeat carrying specific glycans at specific sites. Based on these results, larger amounts of an extended repertoire of defined MUC1 glycopeptides were synthesised, printed on microarrays, and screened with sera from a large cohort of breast cancer patients (n = 395), patients with benign breast disease (n = 108) and healthy controls (n = 99). All sera were collected in the 1970s and 1980s and complete clinical follow-up of breast cancer patients is available. The presence and level of autoantibodies was significantly higher in the sera from cancer patients compared with the controls, and a highly significant correlation with age was observed. High levels of a subset of autoantibodies to the core3MUC1 (GlcNAcβ1-3GalNAc-MUC1) and STnMUC1 (NeuAcα2,6GalNAc-MUC1) glycoforms were significantly associated with reduced incidence and increased time to metastasis. Autoantibodies to specific cancer associated glycoforms of MUC1 are found more frequently and at higher levels in early stage breast cancer patients than in women with benign breast disease or healthy women. Association of strong antibody response with reduced rate and delay in metastases suggests that autoantibodies can affect disease progression.
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影响因子：
82.9
作者：
LUBIN, R;ZALCMAN, G;SOUSSI, T
通讯作者：
SOUSSI, T
影响因子：
4.3
作者：
Sorensen, AL;Reis, CA;Clausen, H
通讯作者：
Clausen, H
影响因子：
8.4
作者：
Hermsen, B. B. J.;Verheijen, R. H. M.;von Mensdorff-Pouilly, S.
通讯作者：
von Mensdorff-Pouilly, S.
影响因子：
4.1
作者：
Bäckström, M;Link, T;Hansson, GC
通讯作者：
Hansson, GC
影响因子：
11.5
作者：
Sabbatini, Paul J.;Ragupathi, Govind;Livingston, Philip O.
通讯作者：
Livingston, Philip O.