Ovarian cancer is associated with changes in glycosylation in both acute-phase proteins and IgG
Ovarian cancer is associated with changes in glycosylation in both acute-phase proteins and IgG
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DOI：
10.1093/glycob/cwm100
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发表时间：
2007-12-01
期刊：
影响因子：
4.3
通讯作者：
Rudd, Pauline M.
中科院分区：
文献类型：
--
作者：
Saldova, Radka;Royle, Louise;Rudd, Pauline M.
卵巢癌是西方世界女性第四大常见癌症。在一项中试研究中，我们强调了晚期卵巢癌患者血清总糖组的变化，这可能有助于了解疾病的发病机制。这些变化包括核心岩藻糖基化、无半乳糖基双触角聚糖（FA 2）和唾液酸刘易斯x（SLe（x））水平升高。为了进一步研究哪些蛋白质对这些改变有贡献，我们开发了同时分析从2D凝胶（< 1 ng蛋白质）切除的单个点中所含蛋白质糖型的糖基化的技术。患者的急性期蛋白、触珠蛋白、α 1-酸性糖蛋白和α 1-抗胰凝乳蛋白酶含有升高水平的含Sle（x）的糖型亚群。我们还确定，与健康对照相比，患者的IgG重链含有两倍的FA 2水平。血清CA 125是常规使用的唯一生物标志物，并且需要将提高灵敏度和特异性的互补标志物。有一些初步的迹象表明，血清糖组的变化组合可能会改善卵巢癌和良性肿瘤的分离;然而，需要一个更大的研究，使用数据接收器工作特征曲线得出任何确切的结论。
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, alpha 1-acid glycoprotein, and alpha 1-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.