Abstract 5544: New technologies to probe the systems glycobiology of cancer

Abstract A robotic 384 well based platform was developed to release and label the human serum N-glycome. Improved separation of the glycan pool, based on hydrophilic interaction UPLC chromatography combined with mass spectrometry (Waters Corporation) and computer assisted data interpretation (NIBRT Glycobase) enabled us to build a database after assigning the detailed structures of more than 170 N-glycans. The aim of the project was to use these technologies and databases to link glycosylation changes in individual patients’ serum with features of cancer and with changes in a range of other –omics data acquired from the same patients. Alterations in glycosylation in various breast cancers were mapped to changes in the serum glycomes and aligned with genetic, transcriptomic and proteomic data. Pathway analysis showed strong associations between these glycan changes and the –omics data. This revealed that many of the glycan changes are directly associated with pathways involved in cancer metastasis. Our next aim was to demonstrate the feasibility of collecting personalised data from individual patients from each of the –omics analyses to build up a dataset of the changing glycosylation over time. This opens up the possibility of linking these data to explore pathways of disease and, in particular, nodal points where the patient can no longer compensate for the effects of an altered pathway that is leading to disease. To this end, single glycoproteins from 8 controls and 26 ovarian cancer patients were sequentially purified from 5ul of serum on affinity plates and the released glycans were analysed. Rather than the conventional way of looking at markers which compare a patients’ data with averages, the control can now be the blood of the patient themselves taken at an earlier time point. The automation, sensitivity, quantitation and resolution of the new technology platforms coupled with dedicated software open up new possibilities for precision medicine and early intervention based on the biochemical profile of the patient. References: Association of N-glycosylation with breast carcinoma and systemic features using high-resolution quantitative UPLC. Saldova R, Asadi Shehni A, Haakensen VD, Steinfeld I, Hilliard M, Kifer I, Helland A, Yakhini Z, Børresen-Dale AL, Rudd PM. J Proteome Res. 2014 May 2;13(5):2314-27. Serum N-glycan analysis in breast cancer patients–Relation to tumour biology and clinical outcome. Haakensen VD, Steinfeld I, Saldova R, Shehni AA, Kifer I, Naume B, Rudd PM, Børresen-Dale AL,Yakhini Z. Mol Oncol. 2016 Jan;10(1):59-72.   Citation Format: Pauline M. Rudd, Mark Hilliard, Mohankumar Muniyappa, Roisin O'Flaherty, Radka Saldova. New technologies to probe the systems glycobiology of cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5544. doi:10.1158/1538-7445.AM2017-5544