Inter-tumor heterogeneity is a result of genomic, transcriptional, translational, and post-translational molecular features. To investigate the roles of protein glycosylation in the heterogeneity of high-grade serous ovarian carcinoma (HGSC), we perform mass spectrometry-based glycoproteomic characterization of 119 TCGA HGSC tissues. Cluster analysis of intact glycoproteomic profiles delineates 3 major tumor clusters and 5 groups of intact glycopeptides. It also shows a strong relationship between N-glycan structures and tumor molecular subtypes, one example of which being the association of fucosylation with mesenchymal subtype. Further survival analysis reveals that intact glycopeptide signatures of mesenchymal subtype are associated with a poor clinical outcome of HGSC. In addition, we study the expression of mRNAs, proteins, glycosites, and intact glycopeptides, as well as the expression levels of glycosylation enzymes involved in glycoprotein biosynthesis pathways in each tumor. The results show that glycoprotein levels are mainly controlled by the expression of their individual proteins, and, furthermore, that the glycoprotein-modifying glycans correspond to the protein levels of glycosylation enzymes. The variation in glycan types further shows coordination to the tumor heterogeneity. Deeper understanding of the glycosylation process and glycosylation production in different subtypes of HGSC may provide important clues for precision medicine and tumor-targeted therapy.

肿瘤间异质性是基因组，转录，翻译和翻译后分子特征的结果。要研究蛋白质糖基化在高级浆液性卵巢癌（HGSC）的异质性中的作用，我们对119 TCGA HGSC组织进行了基于质谱的糖蛋白组学表征。完整的糖蛋白组学图谱的聚类分析描绘了3个主要的肿瘤簇和5组完整的糖肽。它还显示了N-聚糖结构与肿瘤分子亚型之间的密切关系，其中一个实例是岩藻糖基化与间充质亚型的关联。进一步的生存分析表明，间充质亚型的完整糖肽标记与HGSC的不良临床预后相关。此外，我们研究了mRNA，蛋白质，糖基的表达，和完整的糖肽，以及每个肿瘤中糖蛋白生物合成途径中涉及的糖基化酶的表达水平。结果表明，糖蛋白水平主要受其各自蛋白的表达控制，此外，糖蛋白修饰聚糖对应于糖基化酶的蛋白水平。聚糖类型的变化进一步显示出与肿瘤异质性的协调。对HGSC不同亚型中糖基化过程和糖基化产生的更深入了解可能为精密医学和肿瘤靶向治疗提供重要线索。结果表明，糖蛋白水平主要受其各自蛋白的表达控制，此外，糖蛋白修饰聚糖对应于糖基化酶的蛋白水平。聚糖类型的变化进一步显示出与肿瘤异质性的协调。对HGSC不同亚型中糖基化过程和糖基化产生的更深入了解可能为精密医学和肿瘤靶向治疗提供重要线索。结果表明，糖蛋白水平主要受其各自蛋白的表达控制，此外，糖蛋白修饰聚糖对应于糖基化酶的蛋白水平。聚糖类型的变化进一步显示出与肿瘤异质性的协调。对HGSC不同亚型中糖基化过程和糖基化产生的更深入了解可能为精密医学和肿瘤靶向治疗提供重要线索。