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.