Oral Presentation 28th Annual Lorne Proteomics Symposium 2023

Development of a lectin bead-based diagnostic test for oesophageal cancer (#44)

Marisa Duong 1 , Scott Bringans 1 , Katherine Chen 1 , Richard Lipscombe 1 , Michelle Hill 2
  1. Proteomics International, Broadway, Nedlands, WA, Australia
  2. QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia

The 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. These are often only performed when obvious symptoms have manifested, typically at a late stage disease progression. A targeted mass spectrometry-based assay was developed to analyse serum samples for oesophageal adenocarcinoma and Barrett’s oesophagus. The assay was based around a magnetic bead bound lectin that pulls down glycoproteins with specific sugar moieties before digestion and LCMS analysis. The method was automated and optimised to measure 33 target peptides in the lectin pulldown in a short 20 minute mass spectrometry run. Analysis of an initial cohort (n=50) showed 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%. The panel of serum protein biomarkers that were measured correlated with the presence of early stage oesophageal adenocarcinoma (high grade dysplasia). A larger cohort (n=266) was analysed and used to build statistical models which distinguished between disease status, using protein biomarker measurements and simple clinical parameters. Several developed models achieved good discrimination with AUROC values ranging from 0.89-0.97.  Validation of the models was undertaken in the smaller cohort, with the two best performing models achieving AUROC values of 0.82 and 0.87. This proteomics based 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.