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卵巢癌中N-聚糖生物合成途径的聚焦糖组学分析。

Focused glycomic analysis of the N-linked glycan biosynthetic pathway in ovarian cancer.

作者信息

Abbott Karen L, Nairn Alison V, Hall Erica M, Horton Marc B, McDonald John F, Moremen Kelley W, Dinulescu Daniela M, Pierce Michael

机构信息

Complex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, USA.

出版信息

Proteomics. 2008 Aug;8(16):3210-20. doi: 10.1002/pmic.200800157.

Abstract

Epithelial ovarian cancer is the deadliest female reproductive tract malignancy in Western countries. Less than 25% of cases are diagnosed when the cancer is confined, however, pointing to the critical need for early diagnostics for ovarian cancer. Identifying the changes that occur in the glycome of ovarian cancer cells may provide an avenue to develop a new generation of potential biomarkers for early detection of this disease. We performed a glycotranscriptomic analysis of endometrioid ovarian carcinoma using human tissue, as well as a newly developed mouse model that mimics this disease. Our results show that the N-linked glycans expressed in both nondiseased mouse and human ovarian tissues are similar; moreover, malignant changes in the expression of N-linked glycans in both mouse and human endometrioid ovarian carcinoma are qualitatively similar. Lectin reactivity was used as a means for rapid validation of glycan structural changes in the carcinomas that were predicted by the glycotranscriptome analysis. Among several changes in glycan expression noted, the increase of bisected N-linked glycans and the transcripts of the enzyme responsible for its biosynthesis, GnT-III, was the most significant. This study provides evidence that glycotranscriptome analysis can be an important tool in identifying potential cancer biomarkers.

摘要

上皮性卵巢癌是西方国家最致命的女性生殖道恶性肿瘤。然而,不到25%的病例在癌症局限时被诊断出来,这表明对卵巢癌进行早期诊断至关重要。识别卵巢癌细胞糖组中发生的变化可能为开发新一代潜在的早期检测该疾病的生物标志物提供一条途径。我们使用人体组织以及一种新开发的模拟该疾病的小鼠模型,对子宫内膜样卵巢癌进行了糖转录组分析。我们的结果表明,未患病的小鼠和人类卵巢组织中表达的N-连接聚糖相似;此外,小鼠和人类子宫内膜样卵巢癌中N-连接聚糖表达的恶性变化在性质上相似。凝集素反应性被用作快速验证糖转录组分析预测的癌中聚糖结构变化的一种手段。在观察到的聚糖表达的若干变化中,平分型N-连接聚糖及其生物合成负责酶GnT-III的转录本增加最为显著。这项研究提供了证据,表明糖转录组分析可以成为识别潜在癌症生物标志物的重要工具。

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