Development of EndoScreen chip, a microfluidic pre-endoscopy triage test for esophageal adenocarcinoma

Webster, Julie A., Wuethrich, Alain, Shanmugasundaram, Karthik B., Richards, Renee S., Zelek, Wioleta M., Shah, Alok K., Gordon, Louisa G., Kendall, Bradley J., Hartel, Gunter, Morgan, B. Paul ORCID: https://orcid.org/0000-0003-4075-7676, Trau, Matt and Hill, Michelle M. 2021. Development of EndoScreen chip, a microfluidic pre-endoscopy triage test for esophageal adenocarcinoma. Cancers 13 (12) , 2865. 10.3390/cancers13122865

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Abstract

The current endoscopy and biopsy diagnosis of esophageal adenocarcinoma (EAC) and its premalignant condition Barrett’s esophagus (BE) is not cost-effective. To enable EAC screening and patient triaging for endoscopy, we developed a microfluidic lectin immunoassay, the EndoScreen Chip, which allows sensitive multiplex serum biomarker measurements. Here, we report the proof-of-concept deployment for the EAC biomarker Jacalin lectin binding complement C9 (JAC-C9), which we previously discovered and validated by mass spectrometry. A monoclonal C9 antibody (m26 3C9) was generated and validated in microplate ELISA, and then deployed for JAC-C9 measurement on EndoScreen Chip. Cohort evaluation (n = 46) confirmed the expected elevation of serum JAC-C9 in EAC, along with elevated total serum C9 level. Next, we asked if the small panel of serum biomarkers improves detection of EAC in this cohort when used in conjunction with patient risk factors (age, body mass index and heartburn history). Using logistic regression modeling, we found that serum C9 and JAC-C9 significantly improved EAC prediction from AUROC of 0.838 to 0.931, with JAC-C9 strongly predictive of 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). This proof-of-concept study confirms the microfluidic EndoScreen Chip technology and supports the potential utility of blood biomarkers in improving triaging for diagnostic endoscopy. Future work will expand the number of markers on EndoScreen Chip from our list of validated EAC biomarkers.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Additional Information:	This is an open access article distributed under the Creative Commons Attribution License (https:// creativecommons.org/licenses/by/ 4.0/).
Publisher:	MDPI
ISSN:	2072-6694
Date of First Compliant Deposit:	21 June 2022
Date of Acceptance:	21 June 2021
Last Modified:	09 May 2023 02:04
URI:	https://orca.cardiff.ac.uk/id/eprint/150551

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