Jordana Sheahan, Iris Wang, Peter Galettis, David I. Watson, Virendra Joshi, Michelle M. Hill,...
A Clinical Validation of a Diagnostic Test for Esophageal Adenocarcinoma Based on a Novel Serum Glycoprotein Biomarker Panel: PromarkerEso
Jordana Sheahan, Iris Wang, Peter Galettis, David I. Watson, Virendra Joshi, Michelle M. Hill, Richard Lipscombe, Kirsten Peters and Scott Bringans
Abstract
Background: Esophageal adenocarcinoma (EAC) diagnosis involves invasive and expensive endoscopy with biopsy, but rising EAC incidence has not been reduced by increased surveillance. This study aimed to develop and clinically validate a novel glycoprotein biomarker blood test for EAC, named PromarkerEso.
Methods: Serum glycoprotein relative concentrations were measured using a lectin-based magnetic bead array pulldown method, with multiple reaction monitoring mass spectrometry in 259 samples across three independent cohorts. A panel of glycoproteins: alpha-1-antitrypsin, alpha1-antichymotrypsin, complement C9 and plasma kallikrein, were combined with clinical factors (age, sex and BMI) in an algorithm to categorize the samples by the risk of EAC.
Results: PromarkerEso demonstrated a strong discrimination of EAC from the controls (area under the curve (AUC) of 0.91 in the development cohort and 0.82 and 0.98 in the validation cohorts). The test exhibited a high sensitivity for EAC (98% in the development cohort, and 99.9% and 91% in the validation cohorts) and a high specificity (88% in the development cohort, and 86% and 99% in the validation cohorts). PromarkerEso identified individuals with and without EAC (96% and 95% positive and negative predictive values).
Conclusions: This less invasive approach for EAC detection with the novel combination of these glycoprotein biomarkers and clinical factors coalesces in a potential step toward
improved diagnosis.