Towards a blood test for oesophageal adenocarcinoma: Serum glycoprotein biomarker candidates for oesophageal adenocarcinoma — ASN Events
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Towards a blood test for oesophageal adenocarcinoma: Serum glycoprotein biomarker candidates for oesophageal adenocarcinoma (#201)

Alok Shah 1 2 , Kim-Anh Le Cao 1 2 , David Chen 3 , Eunju Choi 1 2 , Benoit Gautier 1 2 , Derek Nancarrow 4 , David Whiteman 4 , Nicholas Saunders 1 2 , Andrew Barbour 2 5 , Virendra Joshi 6 , Michelle Hill 1 2
  1. UQ Diamantina Institute, The University of Queensland, Brisbane, QLD, Australia
  2. Translational Research Institute, Brisbane, QLD, Australia
  3. School of Information and Communication Technology, Griffith University, Brisbane, QLD, Australia
  4. QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
  5. School of Medicine, The University of Queensland, Brisbane, QLD, Australia
  6. Gastroenterology, Ochsner Health System, New Orleans, LA, United States

While the incidence of most cancers are now steadying or declining, oesophageal adenocarcinoma (EAC) continues an upward trend. Rapid increase in EAC is not due to improved diagnosis, but attributed to the increased prevalence of risk factors gastro-esophageal reflux and obesity. Despite aggressive treatment, the survival rate for EAC is low at 9-24% five years post-diagnosis. The precursor condition, Barrett’s oesophagus (BE), affects 0.2-2% of the adult population and increases EAC risk 30-100 fold. However, due to the low conversion rate of BE to EAC, studies indicate that current endoscopic screening programs may not be beneficial. Furthermore, a significant proportion of EAC patients do not have prior BE diagnosis, hence there is an urgent need for better detection of EAC. Our goal is to develop blood biomarker panels that can be used to screen at-risk patients, with positive or suspicious results triggering follow-on endoscopic screening.

We focused on alterations in circulatory protein glycosylation, using a panel of 20 lectins to enrich serum glycoproteins based on their glycan structures. Serum samples from healthy, BE and EAC patients (n=108) were analyzed by lectin magnetic bead array (LeMBA)1, 2-coupled biomarker discovery (LeMBA-QTOF-GlycoSelector http://glycoselector.di.uq.edu.au/index.php) and verification (LeMBA-MRM-MS-Shiny mixOmics http://mixomics-projects.di.uq.edu.au/Shiny/) pipeline.3

We have identified a list of putative serum glycoprotein biomarker that distinguish a) EAC from BE and b) EAC from healthy phenotypes. A multivariate panel achieved area under the receiver operating curve (AUROC) over 0.9, indicative of high diagnostic value. Selected biomarker candidates were further validated using an orthogonal technique, immunoblotting. The results indicate alteration of complement pathway in EAC pathogenesis. Currently we are evaluating the biomarker candidates in an independent patient cohort including early stage EAC patients. Continuing work will also evaluate performance of the biomarker panel to predict therapeutic response.

[1] Loo et al., J Proteome Res 2010

[2] Choi et al., Electrophoresis 2011

[3] Shah et al., Mol Cell Proteomics 2015