Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

EndoScreen Chip: Serum Complement C9 Immunoassays Improve Risk Prediction and Early Diagnosis of Esophageal Adenocarcinoma

Version 1 : Received: 11 March 2021 / Approved: 12 March 2021 / Online: 12 March 2021 (08:03:55 CET)

How to cite: Webster, J.A.; Wuethrich, A.; Shanmugasundaram, K.B.; Richards, R.S.; Zelek, W.M.; Shah, A.K.; Gordon, L.; Kendall, B.J.; Hartel, G.; Morgan, B.P.; Trau, M.; Hill, M.M. EndoScreen Chip: Serum Complement C9 Immunoassays Improve Risk Prediction and Early Diagnosis of Esophageal Adenocarcinoma. Preprints 2021, 2021030330 (doi: 10.20944/preprints202103.0330.v1). Webster, J.A.; Wuethrich, A.; Shanmugasundaram, K.B.; Richards, R.S.; Zelek, W.M.; Shah, A.K.; Gordon, L.; Kendall, B.J.; Hartel, G.; Morgan, B.P.; Trau, M.; Hill, M.M. EndoScreen Chip: Serum Complement C9 Immunoassays Improve Risk Prediction and Early Diagnosis of Esophageal Adenocarcinoma. Preprints 2021, 2021030330 (doi: 10.20944/preprints202103.0330.v1).

Abstract

Esophageal adenocarcinoma (EAC) detection relies on endoscopy-biopsy diagnosis, with routine endoscopic surveillance recommended for Barrett’s esophagus (BE) patients. Here, we examine the utility of blood biomarkers in patient risk stratification by translating the EAC blood biomarker Jacalin lectin binding complement C9 (JAC-C9) into a novel microfluidic immunoassay, the EndoScreen Chip. Cohort evaluation (n=46) showed elevated serum total C9 and JAC-C9 in EAC. Logistic regression modeling demonstrated that addition of C9 and JAC-C9 to patient risk factors (age, body mass index and heartburn/reflux history) improved EAC prediction from AUROC of 0.838 to 0.931. Serum JAC-C9 strongly predicted EAC (vs BE OR= 4.6, 95% CI: 1.6-15.6, p = 0.014; vs Healthy OR=4.1, 95% CI:1.2-13.7, p = 0.024) while total C9 was moderately predictive for BE (vs EAC OR=1.4; 95% CI: 1.0-1.8, p = 0.032; vs Healthy OR=0.8; 95% CI: 0.6-1.0, p = 0.039). This translational study demonstrates the potential utility of blood biomarkers in improving triaging for diagnostic endoscopy.

Keywords

Barrett’s esophagus; biomarker; surveillance; screening; surface-enhanced Raman spectroscopy; SERS; complement component; liquid biopsy; lectin; glycoprotein.

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