# A Clinical Validation of a Diagnostic Test for Esophageal Adenocarcinoma Based on a Novel Serum Glycoprotein Biomarker Panel: PromarkerEso

## TL;DR

A new blood test called PromarkerEso can detect esophageal adenocarcinoma with high accuracy, potentially reducing the need for invasive procedures.

## Contribution

A novel serum glycoprotein biomarker panel combined with clinical factors for non-invasive EAC detection is introduced and clinically validated.

## Key findings

- PromarkerEso achieved an AUC of 0.91 in the development cohort and 0.82 and 0.98 in the validation cohorts.
- The test demonstrated high sensitivity (up to 99.9%) and specificity (up to 99%) across cohorts.
- PromarkerEso showed 96% positive and 95% negative predictive values for EAC detection.

## 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, alpha-1-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.