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

PLoS One. 2015 Jun 15;10(6):e0130197. doi: 10.1371/journal.pone.0130197. eCollection 2015.

Abstract

Background: Mucins 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.

Methods: In 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.

Results: The 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).

Conclusion: Mucinous 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma, Mucinous / blood*
  • Adenocarcinoma, Mucinous / pathology
  • Biomarkers, Tumor / blood
  • Blood Group Antigens / blood*
  • Cyst Fluid / chemistry
  • Cyst Fluid / metabolism*
  • Cystadenocarcinoma, Serous / blood*
  • Cystadenocarcinoma, Serous / pathology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Glycoproteins / blood*
  • Humans
  • Mucins / chemistry*
  • Neoplasm Grading
  • Neoplasm Staging
  • Oligosaccharides / chemistry
  • Oligosaccharides / metabolism*
  • Ovarian Neoplasms / blood*
  • Ovarian Neoplasms / pathology
  • Prognosis

Substances

  • Biomarkers, Tumor
  • Blood Group Antigens
  • Glycoproteins
  • Mucins
  • Oligosaccharides

Grants and funding

This work was supported by the Swedish Research Council (http://www.vr.se/) (2013-5895 and 2010-5322) the County Council of Västra Götaland (http://www.fou.nu/is/alfgbg/) (ALFGBG-290371 and 437281) and by The Swedish Foundation for International Cooperation in Research and Higher Education (STINT) (http://www.stint.se/en/). The LTQ mass spectrometer was obtained by a grant from the Swedish Research Council (342-2004-4434) and the LTQ Orbitrap was obtained from a grant from Knut and Alice Wallenberg foundation (https://www.wallenberg.com/kaw/en) (KAW2007.0118). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.