Table 1.
Examples of oligosaccharide epitopes expressed by mucin-type glycoproteins.
Table 2.
Clinical and biochemical characteristics of ovarian cyst fluid and tissue samples obtained from patients with mucinous and serous ovarian tumors.
Fig 1.
LC-ESI-MS spectra of O-linked oligosaccharides from mucinous and serous cyst fluids.
Oligosaccharides was released by reductive β-elimination from acidic glycoproteins secreted into ovarian cyst fluids obtained from patients with high- and low-grade mucinous (A,B) and serous (C,D) OEC. Combined spectra of components eluted in the region 14–35 minutes in the chromatogram. Only major peaks identified are indicated. For all identified structures see S1 and S2 Tables. Fig 1A shows high abundant structures in low grade mucinous samples that are terminating with blood group O/H and blood group A, while structures in high grade mucinous (Fig 1B) as well as both low and high grade serous samples are terminating with sialic acid. *N-linked oligosaccharides also observed in the spectra.
Fig 2.
Difference in composition of O-linked oligosaccharides between mucinous and serous ovarian cancer.
Diagrams demonstrating fucosylation (Fuc) (A), sialylation (NeuAc) (B) and sulfation (S) (C) levels of expressed O-linked oligosaccharides (MSAC) from mucinous and serous ovarian cyst fluids. Data (MSAC) is based on MS intensities of structures identified by LC-ESI-MS. Sample order corresponds to order in Table 2.
Fig 3.
Tissue localization of α-fucose, MUC5AC (gel-forming mucin) and MUC16/CA125 (trans-membrane mucin) in benign, low-grade and high-grade serous and mucinous ovarian tumor cells.
The figure shows the tissues from mucinous benign (1M-B), low-grade (7M-Low-IA), high-grade (13M-High-IB) as well as from serous benign (14S-B), low-grade (20S-Low-III), high-grade (21S-High-IIIC) tumors (Table 2). Tissues were stained with lectin (UEA I) against fucose, or mucin specific antibodies (anti-MUC5AC and anti-MUC16).
Table 3.
Mucins identified by mass spectrometry in cyst fluid samples obtained from patients with serous and mucinous ovarian benign tumors and stage I, III EOC.
Fig 4.
Localization of MUC5AC and MUC16 in mucinous adenocarcinoma.
Serial sections from low-grade mucinous adenocarcinoma stage IV (10M-Low-IV) from (left-right) stained against MUC5AC and MUC16. The histological staining indicated that MUC5AC and MUC16 were expressed on discrete areas in the tumor.
Fig 5.
LC-ESI-MS spectrum of O-glycans with high sulfate content.
Ovarian cyst fluid sample were obtained from patient with benign serous cystadenoma (15S-B) (A) and the LC-ESI-MS shows that it contains blood group O/H, sialylated and sulfated structures. Inserted panel shows MS2 spectrum of the [M—H] ion at m/z 1121.5 corresponding to the sulfated blood group H containing structure Fucα1-2Galβ1-(HSO3-)GlcNAcβ1-6(Fucα1-2Galβ1–3)GalNAc-ol (B). Proposed key fragments are indicated in the structure. Keys to the monosaccharide symbols see Fig 1.
Fig 6.
Hierarchical cluster analyses of O-glycans from serous and mucinous ovarian tumors.
The clustering based on three variables Fuc, NeuAc and S (A) and also only the two variables NeuAc and S (B). The variables were evaluated using ROC AUC (C). The dendrograms (A, B) identify mucinous benign, LMPs and low-grade ovarian tumors as a distinct group (the group is marked by red color) separate from serous and high grade mucinous samples (the group marked in black). The exception is the LMP mucinous cyst fluid sample obtained from a non-secretor patient (green color). A separate cluster is generated by the two serous benign samples (violet color).