Novel pancreatic cancer biomarkers
Biological glycosylation refers to the enzymatic modification that attaches glycan carbohydrates to proteins or lipids in the cells. Previous studies have shown that altered protein glycosylation is a hallmark of carcinogenesis. Tumour progression is often accompanied by changes in glycosylation level of the proteins as well as the carbohydrate structures. Studies have revealed modified forms of N- and O-glycosylated glycoproteins in a wide range of cancers. The characterisation of a glycoprotein as a biomarker for monitoring tumour growth could prove invaluable as both the protein and glycan moieties contain important information. The EU-funded GLYCOMARKER (Proteomics based identification of biomarkers and cleavage products in pancreatic cancer using glyco-capture technology) project aimed to develop novel methods for the identification of cancer-associated glycoproteins. The project used new proteomics approaches and mass spectrometry-based studies to find the key determinants in the development of pancreatic ductal adenocarcinoma. Scientists introduced new methodology for the enrichment of the sites of protein modifications using charge-reversal of internal peptides and designed workflows for in-depth analysis of post-translational protein processing. Another methodological development involved a quantitative strategy for proteome-wide analysis of formalin-fixed, paraffin-embedded (FFPE) cancer tissues. The comparison of proteome alterations of renal cell carcinoma and adjacent non-malignant tissues were used as a proof-of-principle application of this methodology. Important novel application included the development of degradomic methodology in FFPE tissues. Degradomics refers to the analysis of the protease and protease-substrate repertoires involved in protein degradation inside the cells and tissues. In contrast to a lot of research in the field of proteomics, degradomics is poorly studied. GLYCOMARKER activities have facilitated further research in this area and they have demonstrated that FFPE does not proteolytically damage proteins.
Keywords
Pancreatic cancer, biomarker, glycosylation, GLYCOMARKER, degradomics
