Jordana Sheahan, Iris Wang, Peter Galettis, Scott Bringans, David Watson, Kirsten Peters, Richard Lipscombe
Diseases of the Esophagus, Volume 38, Issue Supplement_1, August 2025, doaf061.017, https://doi.org/10.1093/dote/doaf061.017
Published: 14 August 2025
Abstract
Background:
Esophageal adenocarcinoma (EAC) is often diagnosed at an advanced stage, leading to poor prognosis. The current standard of care involves endoscopy with biopsy in at-risk populations, which is invasive and expensive, yet increasing endoscopic surveillance programs have failed to significantly reduce EAC mortality. Significant to patient management, the pre-cancerous condition Barrett’s Esophagus with high grade dysplasia (BE-HGD) is often treated promptly upon detection similarly to early stage EAC. This study evaluates an alternative diagnostic strategy using the blood test Promarker®Eso, a previously validated serum glycoprotein biomarker panel for EAC, to detect EAC from stage I-IV and BE-HGD.
Methods:
The study analysed 350 people across two independent cohorts: cohort A compared 89 healthy controls with EAC samples of known stage (I: n = 16, II: n = 23, III: n = 16, IV: n = 3); cohort B compared 40 negative controls with unstaged EAC (n = 48) with n = 115 BE samples. The multivariate PromarkerEso test measures four glycoprotein biomarker concentrations (alpha-1-antitrypsin, alpha-1-antichymotrypsin, complement C9 and plasma kallikrein) using a lectin-based magnetic bead array pulldown method with targeted mass spectrometry, combined with simple clinical data (age, sex, BMI). Samples are categorised by predicted probability scores as low- (<20%), moderate- (20–75%) or high- (>75%) risk of having EAC.
Results:
PromarkerEso exhibited robust discrimination performance for all stages of EAC with a minimum area under the curve (AUC) of 0.97. Concurrently, the test exhibited high sensitivity for EAC in all stages (I: 81%, II: 91%, III: 100%; IV: 100%) and also for BE-HGD (93%). Additionally, BE-HGD alone was well discriminated from cancer-free controls with AUC of 0.89. Results demonstrated the increasing severity of disease is significantly correlated with increasing PromarkerEso test scores (p < 0.0001). When categorised by risk score, PromarkerEso effectively separated healthy controls (98% categorised low risk) from EAC stage I (69% categorised high risk and 19% low risk).
Conclusion:
The PromarkerEso test demonstrates strong performance in diagnosing clinically significant early stage EAC and BE-HGD, offering a non-invasive, cost-effective alternative to current endoscopic surveillance methods. The diagnostic potential of glycoprotein biomarkers to discriminate between at-risk and cancer-free populations, even in early stages of cancer, could significantly improve early detection and patient outcomes. These findings highlight the potential of serum biomarkers as a tool for exposing early cancer and are a step towards improved detection of this challenging disease.
