Poster Presentation HUPO 2019 - 18th Human Proteome Organization World Congress

Differential Glycosylation and Novel N-Glycan Site Analysis of ECM Proteins in Gynaecological Cancers (#440)

Matthew T Briggs 1 , Mark R Condina 1 , Yin Ying Ho 2 , Georgia Arentz 2 , Parul Mittal 2 , Manuela Klingler-Hoffmann 1 , Gurjeet Kaur 3 , Martin K Oehler 4 , Peter Hoffmann 1
  1. Future Industries Institute, The University of South Australia, Mawson Lakes, SA, Australia
  2. The University of Adelaide, Adelaide, SA, Australia
  3. Institute for Research in Molecular Medicine, Universiti Sains , Pulau Pinang, Malaysia
  4. Department of Gynaecological Oncology, Royal Adelaide Hospital, Adelaide, SA, Australia

Gynaecological cancers are a group of cancers that originate from the vulva, vagina, cervix, uterus (endometrium), placenta, fallopian tubes and ovaries in adult women. These cancers are known to undergo an epithelial-mesenchymal transition (EMT) which results in the metastasis of epithelial cells and an increase in their resistance to apoptosis by altering the extracellular matrix (ECM). ECM proteins play an imperative role in cell health as they provide the scaffold upon which cells and tissues are built, hence ECM proteins directly and indirectly influence almost all cellular processes, including cell differentiation, proliferation, and motility. The majority of ECM proteins are known to be glycosylated, which is the most prevalent type of post-translational modification (PTM). In this study, we extracted proteins from cervical, vulvar, endometrial and ovarian cancer tissues with their corresponding normal tissues. These tissues were then treated sequentially with PNGase F, allowing for the analysis of cleaved N-linked glycans, followed by trypsin, allowing for the analysis of tryptic peptides. Furthermore, consecutive tissue sections were treated with trypsin followed by zwitterion chromatography-hydrophilic interaction liquid chromatography (ZIC-HILIC) enrichment, allowing for the analysis of glycopeptides. The N-glycan, tryptic peptide and glycopeptide samples were analysed by liquid chromatography tandem mass spectrometry (LC-MS/MS), in order to identify and quantify the oligosaccharide chains and the N-glycosite of peptides. N-glycosite peptide analysis revealed differential glycosylation of ECM proteins from cancerous and normal tissues. However, further investigation with a larger patient cohort is required to assess and validate these findings.