Identification of candidate biomarkers with cancer-specific glycosylation in the tissue and serum of endometrioid ovarian cancer patients by glycoproteomic analysis.
Identification of candidate biomarkers with cancer-specific glycosylation in the tissue and serum of endometrioid ovarian cancer patients by glycoproteomic analysis.
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DOI：
10.1002/pmic.200900537
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发表时间：
2010-02
期刊：
影响因子：
3.4
通讯作者：
Pierce M
中科院分区：
文献类型：
--
作者：
Abbott KL;Lim JM;Wells L;Benigno BB;McDonald JF;Pierce M
当癌症局限于卵巢时，上皮性卵巢癌的诊断率低于25%，导致5年生存率低于30%。因此，迫切需要对卵巢癌进行早期诊断。我们的研究使用糖转录组对子宫内膜样卵巢癌组织和正常卵巢组织进行比较分析，发现参与N连接糖基化的一组限制性糖基转移酶的转录物存在明显差异。利用凝集素结合的聚糖结构预测显示的变化，我们观察到的凝集素结合的糖蛋白的差异与一些转录差异一致。在这项研究中，我们通过使用选择的凝集素对卵巢癌和正常卵巢组织进行靶向糖蛋白质组学分析来扩展我们的观察。我们的研究结果已经确定了几个糖蛋白，显示肿瘤特异性糖基化的变化。我们已经使用免疫沉淀法和凝集素印迹检测验证了组织糖蛋白上的这些糖基化变化。然后使用从良性卵巢腺瘤、交界性卵巢腺癌和恶性卵巢腺癌获得的现有微阵列数据进一步分析经验证的糖蛋白。然后，在微阵列数据集中发现表达高于对照水平的经验证的糖蛋白在来自卵巢癌患者的血清中筛选肿瘤特异性聚糖修饰。从这些糖蛋白标志物中的两种，骨膜蛋白和血小板反应蛋白获得的结果已经证实，肿瘤特异性聚糖的变化可用于区分卵巢癌患者血清与正常血清。
Epithelial ovarian cancer is diagnosed less than 25% of the time when the cancer is confined to the ovary, leading to 5-year survival rates of less than 30%. Therefore, there is an urgent need for early diagnostics for ovarian cancer. Our study using glycotranscriptome comparative analysis of endometrioid ovarian cancer tissue and normal ovarian tissue led to the identification of distinct differences in the transcripts of a restricted set of glycosyltransferases involved in N-linked glycosylation. Utilizing lectins that bind to glycan structures predicted to show changes, we observed differences in lectin-bound glycoproteins consistent with some of the transcript differences. In this study, we have extended our observations by the use of selected lectins to perform a targeted glycoproteomic analysis of ovarian cancer and normal ovarian tissues. Our results have identified several glycoproteins that display tumor-specific glycosylation changes. We have verified these glycosylation changes on glycoproteins from tissue using immunoprecipitation followed by lectin blot detection. The glycoproteins that were verified were then analyzed further using existing microarray data obtained from benign ovarian adenomas, borderline ovarian adenocarcinomas, and malignant ovarian adenocarcinomas. The verified glycoproteins found to be expressed above control levels in the microarray data sets were then screened for tumor-specific glycan modifications in serum from ovarian cancer patients. Results obtained from two of these glycoprotein markers, periostin and thrombospondin, have confirmed that tumor-specific glycan changes can be used to distinguish ovarian cancer patient serum from normal serum.