Identification of candidate biomarkers with cancer-specific glycosylation in the tissue and serum of endometrioid ovarian cancer patients by glycoproteomic analysis

被引:118
作者
Abbott, Karen L. [1 ,2 ,3 ]
Lim, Jae-Min [1 ,2 ,3 ]
Wells, Lance [1 ,2 ,3 ]
Benigno, Benedict B. [4 ]
McDonald, John F. [4 ,5 ]
Pierce, Michael [1 ,2 ,3 ]
机构
[1] Univ Georgia, Complex Carbohydrate Res Ctr, Athens, GA 30602 USA
[2] Univ Georgia, Dept Biochem & Mol Biol, Athens, GA 30602 USA
[3] Univ Georgia, Dept Chem, Athens, GA 30602 USA
[4] Ovarian Canc Inst, Atlanta, GA USA
[5] Georgia Inst Technol, Sch Biol, Atlanta, GA 30332 USA
关键词
Biomarker; Glycan; Glycoprotein; Glycoproteomics; Ovarian cancer; CELL-CELL ADHESION; FUCOSYLATED GLYCOPROTEINS; CORE FUCOSYLATION; GLYCOMIC ANALYSIS; CARCINOMA; EXPRESSION; ACTIVATION; PROTEINS; STRESS;
D O I
10.1002/pmic.200900537
中图分类号
Q5 [生物化学];
学科分类号
070307 [化学生物学];
摘要
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 glycosyladon. 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.
引用
收藏
页码:470 / 481
页数:12
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