Community Research and Development Information Service - CORDIS


Pancreatic cancer is the fourth most common internal cancer in Europe, with almost 80,000 death per annum. Taken worldwide, there is an annual incidence of over 200,000 pancreatic cancer cases with an annual mortality that is almost equal to the incidence rate. At present, prancreatic cancer consists one of the worst outcomes of all cancers and has a very poor prognosis, often attributed to the absence of sensitive biomarkers, late stage presentation, early recurrence and a lack of effective treatments. GlycoMarker is a two-year study looking at new proteomics approaches and new direction for mass spectrometry-based studies aiming to elucide the key determinants in the development of pancreatic ductal adenocarcinoma. To achieve its objectives, GlycoMarkers has produced research results of high quality and subsequently published them in top international conferences and peer-reviewed journals:
1. Introducing novel methodology for the enrichment of protein amino-termini using charge-reversal of internal peptides. Furthermore, two robust workflows (gel-free and gel-based) were designed to allow in-depth analysis of post-translational processing of proteins.
2. Establishment of a robust quantitative strategy in proteome-wide analysis of formalin-fixed, paraffin-embedded cancer tissues. The study highlights isotopic amine dimethylation of FFPE speciments showed equal labeling efficiency as for cryopreserved specimens. Furthermore, the comparison of proteome alterations of clear cell renal cell carcinoma and adjacent non-malignant renal tissues were used as a proof-of-principle clinical application of this methodology.
3. Characterization of various cancer cell line subtypes and cancer associated fibroblast-mediated responses in Ampullary cancer. Ampullary cancer is a relatively rare form of cancer and usually treated by pancreatoduodenectomy, followed by adjuvant therapy. The study investigated subtype marker expression, EMT features, cellular growth and invasion rates, and drug-sensitivity.
4. Introducing novel application of degradomic methodology in formalin-fixed, paraffin-embedded tissues. This proof-of-concept study demonstrate comparable N-terminomes of cryopreserved and formalin fixed tissue, thereby showing that formalin fixation / paraffin embedment does not proteolytically damage proteins.
5. Whilst there is a lot of research on the field of proteomics and peptidomics, degradomics type research remained to be poorly studied. GlycoMarker has facilitated the understanding of proteolysis via three review articles on the topics of N- and C-terminomics, as well as endogenous peptides and the implication of proteases in diseases.
6. The research results of GlycoMarker facilitated the successful application of two grants; FP7 PRIME-XS Acess Grant and a grant by the German Consortium for Translational Cancer Research as well as the application of an ERC Consolidator Grant on the role of proteases in tumor therapy resistance.

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