卵巢粘液性腺癌分泌性粘蛋白的糖基化修饰与细胞恶性行为相关性研究

Advanced ovarian mucinous adenocarcinoma (mEOC) had the characteristic of secretory mucin on cell surface. The patients were young, and the treatment effect responsing to classic chemotherapy was very poor. In previous work, we found that the methods of hypoglycemic base treatment on the mEOC cell surface could improve the effect of chemotherapy Taxol in vitro and in vivo experiments. But because the great molecular weight and height of mucin glycosylation, glycosylation analysis is very difficult. So the mechanism was still unknown. To clear the expression of glycosylation in different degree of malignancy mEOC, the project intends to combine a series of the latest developments in the field of biological and chemical methods, such as efficient quantitative series 0 mark, composite nanomaterials specific enrichment of glycoprotein, high-capacity and high-resolution liquid chromatography-mass spectrometry isolation and identification technologies, to study secreted mucin in mEOC about N-and O- glycosylation quantitis, sites and glycated chain structure. Our purpose is to figure out the association between glycosylation and malignant behavior and to lay the foundation for further researchs about development characteristics of mEOC and resistance mechanisms.

晚期卵巢粘液性腺癌（mEOC）具有细胞表面产生分泌性粘蛋白的特点，其发病年龄轻，对经典化疗反应极差。在前期工作中我们发现，mEOC细胞表面粘蛋白可起到"糖盔甲"的作用，使其降糖基化可在体内外实验均提高泰素的化疗效果，但因粘蛋白的极大分子量和高度糖基化，其糖基化特征分析困难，因此其中机制不明。为首先明确粘蛋白的糖基化修饰在不同恶性程度mEOC中的表达，本项目拟结合生物及化学领域最新发展的一系列方法，如高效的串联同位素O标记定量、β消除法、高灵敏和高分辨的液质联用分离鉴定等技术研究mEOC分泌性粘蛋白的N-与O-糖基化程度、糖基化位点及糖链结构，归纳与细胞恶性行为密切相关的糖基化特征，明确关键糖基化位点，从而为进一步揭示mEOC发生发展特性及耐药机制奠定基础。

晚期卵巢粘液性腺癌（ mEOC ）具有细胞表面产生分泌性粘蛋白的特点，其发病年龄轻，对经典化疗反应极差。在前期工作中我们发现，mEOC细胞表面粘蛋白可起到“糖盔甲”的作用，降低了化疗效果。故本课题以肿瘤细胞系、动物模型及人类患者的组织标本为研究对象，研究卵巢粘液性腺癌分泌性黏蛋白的糖基化修饰与细胞恶性行为的关系，鉴定了卵巢粘液性腺癌组织的分泌性粘蛋白糖基化位点；研究了粘液在体内外对卵巢癌细胞恶性行为的影响，发现粘蛋白的糖基化与肿瘤细胞的化疗敏感性密切相关；同时发现粘蛋白的高表达提示了卵巢粘液性腺癌患者对化疗药物的低反应性以及不良预后。