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卵巢癌与急性期蛋白和免疫球蛋白G的糖基化变化有关。

Ovarian cancer is associated with changes in glycosylation in both acute-phase proteins and IgG.

作者信息

Saldova Radka, Royle Louise, Radcliffe Catherine M, Abd Hamid Umi M, Evans Rachel, Arnold James N, Banks Rosamonde E, Hutson Richard, Harvey David J, Antrobus Robin, Petrescu Stefana M, Dwek Raymond A, Rudd Pauline M

机构信息

Department of Biochemistry, Oxford Glycobiology Institute, University of Oxford, Oxford, UK.

出版信息

Glycobiology. 2007 Dec;17(12):1344-56. doi: 10.1093/glycob/cwm100. Epub 2007 Sep 20.

Abstract

Ovarian cancer is the fourth most common cancer in women in the Western world. In a pilot scale study, we highlight changes in the total serum glycome of patients with advanced ovarian cancer that might shed insight into disease pathogenesis. These changes include increases in levels of core fucosylated, agalactosyl biantennary glycans (FA2) and sialyl Lewis x (SLe(x)). To investigate further which proteins contribute to these alterations, we developed technology to analyze simultaneously the glycosylation of protein glycoforms contained in single spots excised from a 2D gel (<1 ng protein). The acute-phase proteins, haptoglobin, alpha1-acid glycoprotein, and alpha1-antichymotrypsin from patients contained elevated levels of subsets of glycoforms containing SLe(x). We also established that IgG heavy chains from patients contained twice the level of FA2 compared with healthy controls. Serum CA125 is the only biomarker that is used routinely, and there is a need for complementary markers that will improve both sensitivity and specificity. There was some preliminary indication that combinations of changes in the serum glycome might improve the separation of ovarian cancer and benign tumors; however, a larger study using data receiver operating characteristic curves will be required to draw any firm conclusions.

摘要

卵巢癌是西方世界女性中第四常见的癌症。在一项小规模研究中,我们着重指出了晚期卵巢癌患者血清总糖组的变化,这些变化可能有助于深入了解疾病的发病机制。这些变化包括核心岩藻糖基化、无半乳糖双天线聚糖(FA2)和唾液酸化路易斯x(SLe(x))水平的升高。为了进一步研究哪些蛋白质导致了这些改变,我们开发了一种技术,用于同时分析从二维凝胶上切下的单个斑点(蛋白质含量<1 ng)中蛋白质糖型的糖基化情况。患者的急性期蛋白、触珠蛋白、α1-酸性糖蛋白和α1-抗糜蛋白酶中,含有SLe(x)的糖型亚群水平升高。我们还确定,患者的IgG重链中FA2的水平是健康对照者的两倍。血清CA125是唯一常规使用的生物标志物,因此需要补充性标志物来提高敏感性和特异性。有一些初步迹象表明,血清糖组变化的组合可能会改善卵巢癌与良性肿瘤的鉴别;然而,需要进行一项使用数据接受者操作特征曲线的更大规模研究才能得出任何确凿结论。

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