Oesophageal adenocarcinoma is one of the most rapidly increasing cancers. Gastro-oesophageal reflux and obesity leads to the development of a pre-cancer metaplastic condition, termed Barrett’s oesophagus. Most cases are diagnosed at a late stage, leading to a poor 5-year survival rate of <15%. Barrett’s oesophagus and cancer are currently diagnosed by upper gastro-oesophageal endoscopy with biopsy. This procedure requires patient hospitalisation and specialist appointment and is not suitable for patient screening. The aim of this project is to identify serum biomarkers for early diagnosis of Barrett’s oesophagus and cancer.
APPROACH & METHODOLOGY: We focussed on alterations in protein glycosylation, using a panel of 20 lectins to isolate different glycan structures on serum glycoproteins as we recently reported1. Serum samples from 10 patients each for control, Barrett’s oesophagus and oesophageal adenocarcinoma groups were analysed by lectin magnetic bead array-coupled tandem mass spectrometry (LeMBA-MS/MS) and analysed through a customised database incorporating outlier detection and sparse Partial Least Squares regression Discriminant Analysis2.
RESULTS & DISCUSSION: We identified a ranked list of candidate glycobiomarkers that distinguish a) cancer from Barrett’s oesophagus and b) Barrett’s oesophagus from control group. In general, glycoproteins bound several lectins, reflecting heterogeneity and multiplicity of glycosylation. Specific glycan structure changes were observed as loss and gain of binding to a single lectin while maintaining binding to other lectins. Future work will validate the candidate protein-lectin pairs using a customised lectin-affinity array-coupled with quantitative mass spectrometry measurements for an independent cohort of 100+ patients. The specificity and sensitivity of panels of glycobiomarkers will be determined for formulating a serum screening test for Barrett’s oesophagus and oesophageal adenocarcinoma.