Translational Research Group, University Hospital Zurich, Zurich, Switzerland.
Int J Cancer. 2012 Jan 1;130(1):138-46. doi: 10.1002/ijc.26002. Epub 2011 Apr 25.
Epithelial ovarian cancer has the highest mortality rate among gynecological cancers. Altered glycosylation is associated with oncogenic transformation producing tumor-associated carbohydrate antigens. We investigated the potential of natural occurring antiglycan antibodies in the diagnosis of ovarian cancer by using printed glycan array. Antiglycan antibodies bound to 203 chemically synthesized printed glycans were detected via biotin-streptavidin fluorescence system in serum of women with normal operative findings (healthy controls; n = 24) and nonmucinous borderline or ovarian cancer of various FIGO stages (n = 33). Data were validated measuring blood group associated di-, tri and tetrasaccharide antigens on known ABO blood groups. Antiglycan antibodies demonstrated high reproducibility (r(c) > 0.9). Cluster analysis identified repetitive patterns of specific core carbohydrate structures: 11 N-linked glycans, 3 O-linked glycans and 2 glycosphingolipids. Biomarker detection revealed 24 glycans including P(1) (Galα1-4Galβ1-4GlcNAcβ; p < 0.001) significantly discriminating between (low-) malignant tumors and healthy controls. Comparable sensitivity and specificity with tumor marker CA125 was achieved by a panel of multivariate selected and linear combined antiglycan antibody signals (79.2 and 84.8%, respectively). Our findings demonstrate the potential of glycan arrays in the development of a new generation of biomarkers for ovarian cancer.
上皮性卵巢癌是妇科癌症中死亡率最高的一种。糖基化的改变与致癌转化有关,产生肿瘤相关的碳水化合物抗原。我们通过使用印刷聚糖阵列来研究天然存在的抗糖抗体在卵巢癌诊断中的潜力。通过生物素-链霉亲和素荧光系统,在具有正常手术结果的女性(健康对照组;n = 24)和非粘液性交界性或各种 FIGO 阶段的卵巢癌(n = 33)的血清中检测到与 203 种化学合成印刷聚糖结合的抗糖抗体。通过测量已知 ABO 血型的血型相关二糖、三糖和四糖抗原来验证数据。抗糖抗体表现出高重现性(r(c) > 0.9)。聚类分析确定了特定核心碳水化合物结构的重复模式:11 种 N-连接聚糖、3 种 O-连接聚糖和 2 种糖脂。生物标志物检测显示 24 种聚糖,包括 P(1)(Galα1-4Galβ1-4GlcNAcβ;p < 0.001),可显著区分低恶性肿瘤和健康对照组。通过多元选择和线性组合的抗糖抗体信号的面板,可以实现与肿瘤标志物 CA125 相当的敏感性和特异性(分别为 79.2%和 84.8%)。我们的研究结果表明,聚糖阵列在开发新一代卵巢癌生物标志物方面具有潜力。