The O-Linked Glycome and Blood Group Antigens ABO on Mucin-Type Glycoproteins in Mucinous and Serous Epithelial Ovarian Tumors

Abstract

BackgroundMucins are heavily O-glycosylated proteins where the glycosylation has been shown to play an important role in cancer. Normal epithelial ovarian cells do not express secreted mucins, but their abnormal expression has previously been described in epithelial ovarian cancer and may relate to tumor formation and progression. The cyst fluids were shown to be a rich source for acidic glycoproteins. The study of these proteins can potentially lead to the identification of more effective biomarkers for ovarian cancer.MethodsIn this study, we analyzed the expression of the MUC5AC and the O-glycosylation of acidic glycoproteins secreted into ovarian cyst fluids. The samples were obtained from patients with serous and mucinous ovarian tumors of different stages (benign, borderline, malignant) and grades. The O-linked oligosaccharides were released and analyzed by negative-ion graphitized carbon Liquid Chromatography (LC) coupled to Electrospray Ionization tandem Mass Spectrometry (ESI-MSn). The LC-ESI-MSn of the oligosaccharides from ovarian cyst fluids displayed differences in expression of fucose containing structures such as blood group ABO antigens and Lewis-type epitopes.ResultsThe obtained data showed that serous and mucinous benign adenomas, mucinous low malignant potential carcinomas (LMPs, borderline) and mucinous low-grade carcinomas have a high level of blood groups and Lewis type epitopes. In contrast, this type of fucosylated structures were low abundant in the high-grade mucinous carcinomas or in serous carcinomas. In addition, the ovarian tumors that showed a high level of expression of blood group antigens also revealed a strong reactivity towards the MUC5AC antibody. To visualize the differences between serous and mucinous ovarian tumors based on the O-glycosylation, a hierarchical cluster analysis was performed using mass spectrometry average compositions (MSAC).ConclusionMucinous benign and LMPs along with mucinous low-grade carcinomas appear to be different from serous and high-grade mucinous carcinomas based on their O-glycan profiles.

Discovery of Pancreatic Ductal Adenocarcinoma-Related Aberrant Glycosylations: A Multilateral Approach of Lectin Microarray-Based Tissue Glycomic Profiling With Public Transcriptomic Datasets

“…These observations are also consistent with the fact that the expression of FUT1 is relatively higher in the pancreas, based on the Tissue Atlas provided by the Human Protein Atlas project (https://www.proteinatlas.org/). ABO blood group antigens are present in many tissues, including the pancreas (50), especially on glycolipids and O-glycoproteins (51,52). We found that the N-glycans of basigin were affected by the PDAC-relevant aberrations in the glycosylation machinery.…”

Histo-blood group glycans in the context of personalized medicine

“…(sialyl-Le a ) levels in clinics [17]. Genotyping, glycosyltransferase transcript analysis as well as standard proteomic techniques are currently being increasingly used also in the context of BG-typing [27, 130], and do therefore comply with the requirements of modern personalized medicine. Furthermore, they might be useful for patient stratification in settings where the genetic histo-BG background in combination with the natural anti-BG antigen antibodies plays a role, such as vaccine efficacy studies.…”

“…However, glycomics of histo-BGs has been neglected in the last years except for some few, rather targeted approaches [153][154][155]. In a very recent study traditional, targeted techniques in combination with liquid-chromatography-MS/MS were successfully applied showing great potential of mucin-type histo-BG glycans for ovarian tumor staging and classification not only from tissues, but also from cystic fluid [130]. Glycomic approaches on only minute amounts of preferably non-invasively acquired patient samples, such as saliva, tears, milk, urine, or feces [66,[156][157][158][159], will be of particular use in the context of early diagnosis and population-wide screening.…”

Molecular similarities and differences from human pulmonary fibrosis and corresponding mouse model: MALDI imaging mass spectrometry in comparative medicine

“…Changing of glycosylation in cystic fluids is already showing a potential for ovarian tumor staging and classification. 27 Most of the shared molecules were comparably abundant in the two tissues (Figures 6a and b), which suggests a highly functional molecular overlap between fibrotic disease in humans and the induced fibrotic mouse model. Molecules that were comparably abundant in humans and mice were annotated and subsequently analyzed for pathway enrichment.…”