Oesophageal adenocarcinoma is one of the most rapidly increasing and deadly cancers in the world. Gastro-oesophageal reflux and obesity leads to the development of a pre-cancer metaplastic condition, termed Barrett’s oesophagus. Diagnosis of Barrett’s oesophagus and cancer currently require upper gastro-oesophageal endoscopy with biopsy. This procedure requires hospital and specialist appointment and is not suitable for patient screening. To facilitate early diagnosis, the aim of this project is to identify a panel of serum biomarkers for 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 reported (1). 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). A customised database was developed which incorporates outlier detection and sparse Partial Least Squares regression Discriminant Analysis (2).
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.