203. ESTABLISHING A MASS SPECTROMETRY BASED DIAGNOSTIC TEST FOR OESOPHAGEAL CANCER

Abstract Diagnosis of oesophageal adenocarcinoma, or Barrett’s oesophagus, a pre-malignant condition associated with an increased risk of the adenocarcinoma, currently requires expensive and invasive endoscopy-biopsy procedures, which are often only performed when obvious symptoms have manifested (usually at a late stage of the disease). A targeted mass spectrometry-based method was developed to analyse serum samples for oesophageal adenocarcinoma. Panels of lectin-pulled down serum protein biomarkers were identified that correlate with the presence of early stage oesophageal adenocarcinoma (high grade dysplasia). The method was automated and optimised the methodology to measure 33 target peptides in the lectin pulldown in a short 20 minute mass spectrometry run. Analysis of an initial cohort (n = 50) shows the method to be robust and reproducible with an average intraday CV of 9.3% across the 33 peptides and an average interday CV of 11.5%. A larger cohort (n = 266) showed consistent results and was used to build statistical models which distinguished between disease status, using protein biomarker measurements and simple clinical parameters. Several models achieved good discrimination with AUROC values ranging from 0.89–0.97. Model validation was undertaken in the smaller cohort, with the two best performing models achieving AUROC values of 0.82 and 0.87. The assay has the potential to produce a clinically viable diagnostic test to support screening and early detection in populations at high risk of oesophageal adenocarcinoma and Barrett’s oesophagus.