Identification of glycoproteins associated with different histological subtypes of ovarian tumors using quantitative glycoproteomics.

Identification of glycoproteins associated with different histological subtypes of ovarian tumors using quantitative glycoproteomics.
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DOI:
10.1002/pmic.201000811
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发表时间:
2011-12
期刊:
影响因子:
3.4
通讯作者:
Zhang, Hui
Zhang, Hui
中科院分区:
生物学3区
文献类型:
--
作者:
Tian, Yuan;Yao, Zhihao;Roden, Richard B. S.;Zhang, Hui

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卵巢癌是成年女性中最致命的妇科恶性肿瘤。上皮性卵巢肿瘤的起源在形态学和生物学上都是异质性的,并且不同亚型的卵巢肿瘤具有不同的临床结局。尽管卵巢癌的异质性,目前的生物标志物和治疗这种疾病的亚型特异性。为了揭示卵巢肿瘤亚型的分子基础,我们采用定量糖蛋白质组学方法分析了7种常见亚型和正常卵巢组织的胞外糖蛋白。通过液相色谱-串联质谱法鉴定不同卵巢肿瘤亚型的糖蛋白,并通过光谱计数进行定量,然后通过iTRAQ标记和Western印迹进行验证。糖蛋白在卵巢肿瘤的不同亚型中唯一表达或在大多数亚型中普遍表达。使用蛋白质印迹,我们验证了间皮素在浆液性癌和过渡细胞癌中过表达,CEA 5和CEA 6仅在粘液性癌中过表达,而versican和periostin在大多数卵巢肿瘤亚型中过表达。这项研究代表了不同卵巢肿瘤亚型的第一个蛋白质组学特征。鉴定的卵巢肿瘤组织学亚型的糖蛋白将有助于理解卵巢肿瘤亚型的分子基础、诊断和预测对治疗剂的治疗反应。
Ovarian cancer is the most lethal gynecologic malignancy in adult women. The origin of epithelial ovarian tumors is both morphologically and biologically heterogeneous, and different subtypes of ovarian tumors have different clinical outcomes. In spite of the heterogeneous nature of ovarian carcinoma, the current biomarkers and treatments for this disease are not subtype-specific. To discover the molecular basis of the ovarian tumor subtypes, we analyzed extracellular glycoproteins of seven common subtypes and normal ovary tissues using quantitative glycoproteomic analysis. Glycoproteins for different ovarian tumor subtypes were identified by liquid chromatography-tandem mass spectrometry and quantitated by spectral counting and then verified by iTRAQ labeling and Western blotting. Glycoproteins uniquely expressed in different subtypes of ovarian tumors or commonly expressed in most subtypes were identified. Using Western blots, we verified that mesothelin was overexpressed in serous carcinoma and transitional-cell carcinoma, CEA5 and CEA6 were overexpressed only in mucinous carcinoma, while versican and periostin were overexpressed in most subtypes of ovarian tumors. This study represents the first proteomic characterization of different ovarian tumor subtypes. The identified glycoproteins for histological subtypes of ovarian tumors will facilitate the understanding of the molecular basis, diagnosis of ovarian tumor subtypes, and predictions for treatment responses to therapeutic agents.
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