Liquid biopsy to identify Barrett’s oesophagus, dysplasia and oesophageal adenocarcinoma: the EMERALD multicentre study

Jinsei Miyoshi; Alessandro Mannucci; Marco Scarpa; Feng Gao; Shusuke Toden; Timothy Whitsett; Landon J Inge; Ross M Bremner; Tetsuji Takayama; Yulan Cheng; Teodoro Bottiglieri; Iris D Nagetaal; Martha J Shrubsole; Ali H Zaidi; Xin Wang; Helen G Coleman; Lesley A Anderson; Stephen J Meltzer; Ajay Goel; FINBAR-EMERALD collaborative group

doi:10.1136/gutjnl-2024-333364

Liquid biopsy to identify Barrett’s oesophagus, dysplasia and oesophageal adenocarcinoma: the EMERALD multicentre study

Jinsei Miyoshi, Alessandro Mannucci, Marco Scarpa, Feng Gao, Shusuke Toden, Timothy Whitsett, Landon J Inge, Ross M Bremner, Tetsuji Takayama, Yulan Cheng, Teodoro Bottiglieri, Iris D Nagetaal, Martha J Shrubsole, Ali H Zaidi, Xin Wang, Helen G Coleman, Lesley A Anderson, Stephen J Meltzer, Ajay Goel, FINBAR-EMERALD collaborative group

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Abstract

BACKGROUND: There is no clinically relevant serological marker for the early detection of oesophageal adenocarcinoma (EAC) and its precursor lesion, Barrett's oesophagus (BE).

OBJECTIVE: To develop and test a blood-based assay for EAC and BE.

DESIGN: Oesophageal MicroRNAs of BaRRett, Adenocarcinoma and Dysplasia (EMERALD) was a large, international, multicentre biomarker cohort study involving 792 patient samples from 4 countries (NCT06381583) to develop and validate a circulating miRNA signature for the early detection of EAC and high-risk BE. Tissue-based miRNA sequencing and microarray datasets (n=134) were used to identify candidate miRNAs of diagnostic potential, followed by validation using 42 pairs of matched cancer and normal tissues. The usefulness of the candidate miRNAs was initially assessed using 108 sera (44 EAC, 34 EAC precursors and 30 non-disease controls). We finally trained a machine learning model (XGBoost+AdaBoost) on RT-qPCR results from circulating miRNAs from a training cohort (n=160) and independently tested it in an external cohort (n=295).

RESULTS: After a strict process of biomarker discovery and selection, we identified six miRNAs that were overexpressed in all sera of patients compared with non-disease controls from three independent cohorts of different nationalities (miR-106b, miR-146a, miR-15a, miR-18a, miR-21 and miR-93). We established a six-miRNA diagnostic signature using the training cohort (area under the receiver operating characteristic curve (AUROC): 97.6%) and tested it in an independent cohort (AUROC: 91.9%). This assay could also identify patients with BE among patients with gastro-oesophageal reflux disease (AUROC: 94.8%, sensitivity: 92.8%, specificity: 85.1%).

CONCLUSION: Using a comprehensive approach integrating unbiased genome-wide biomarker discovery and several independent experimental validations, we have developed and validated a novel blood test that might complement screening options for BE/EAC.

TRIAL REGISTRATION NUMBER: NCT06381583

Original language	English
Pages (from-to)	169-181
Journal	Gut
Volume	74
Issue number	2
Early online date	19 Nov 2024
DOIs	https://doi.org/10.1136/gutjnl-2024-333364
Publication status	Published - 17 Jan 2025

Bibliographical note

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This work is licensed under Queen’s Research Publications and Copyright Policy.

Keywords

Liquid biopsy
Barrett’s oesophagus
dysplasia
oesophageal adenocarcinoma

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Liquid biopsy to identify Barrett’s oesophagus, dysplasia and oesophageal adenocarcinoma: the EMERALD multicentre study
Copyright 2025 the authors. This is an accepted manuscript distributed under a Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
Accepted author manuscript, 637 KBLicence: CC BY

Cite this

Miyoshi, J., Mannucci, A., Scarpa, M., Gao, F., Toden, S., Whitsett, T., Inge, L. J., Bremner, R. M., Takayama, T., Cheng, Y., Bottiglieri, T., Nagetaal, I. D., Shrubsole, M. J., Zaidi, A. H., Wang, X., Coleman, H. G., Anderson, L. A., Meltzer, S. J., Goel, A., & FINBAR-EMERALD collaborative group (2025). Liquid biopsy to identify Barrett’s oesophagus, dysplasia and oesophageal adenocarcinoma: the EMERALD multicentre study. Gut, 74(2), 169-181. https://doi.org/10.1136/gutjnl-2024-333364

@article{7a96a2e06f76488296ecbcf2522e4ed3,

title = "Liquid biopsy to identify Barrett{\textquoteright}s oesophagus, dysplasia and oesophageal adenocarcinoma: the EMERALD multicentre study",

abstract = "BACKGROUND: There is no clinically relevant serological marker for the early detection of oesophageal adenocarcinoma (EAC) and its precursor lesion, Barrett's oesophagus (BE).OBJECTIVE: To develop and test a blood-based assay for EAC and BE.DESIGN: Oesophageal MicroRNAs of BaRRett, Adenocarcinoma and Dysplasia (EMERALD) was a large, international, multicentre biomarker cohort study involving 792 patient samples from 4 countries (NCT06381583) to develop and validate a circulating miRNA signature for the early detection of EAC and high-risk BE. Tissue-based miRNA sequencing and microarray datasets (n=134) were used to identify candidate miRNAs of diagnostic potential, followed by validation using 42 pairs of matched cancer and normal tissues. The usefulness of the candidate miRNAs was initially assessed using 108 sera (44 EAC, 34 EAC precursors and 30 non-disease controls). We finally trained a machine learning model (XGBoost+AdaBoost) on RT-qPCR results from circulating miRNAs from a training cohort (n=160) and independently tested it in an external cohort (n=295).RESULTS: After a strict process of biomarker discovery and selection, we identified six miRNAs that were overexpressed in all sera of patients compared with non-disease controls from three independent cohorts of different nationalities (miR-106b, miR-146a, miR-15a, miR-18a, miR-21 and miR-93). We established a six-miRNA diagnostic signature using the training cohort (area under the receiver operating characteristic curve (AUROC): 97.6%) and tested it in an independent cohort (AUROC: 91.9%). This assay could also identify patients with BE among patients with gastro-oesophageal reflux disease (AUROC: 94.8%, sensitivity: 92.8%, specificity: 85.1%).CONCLUSION: Using a comprehensive approach integrating unbiased genome-wide biomarker discovery and several independent experimental validations, we have developed and validated a novel blood test that might complement screening options for BE/EAC.TRIAL REGISTRATION NUMBER: NCT06381583",

keywords = "Liquid biopsy, Barrett{\textquoteright}s oesophagus, dysplasia, oesophageal adenocarcinoma",

author = "Jinsei Miyoshi and Alessandro Mannucci and Marco Scarpa and Feng Gao and Shusuke Toden and Timothy Whitsett and Inge, {Landon J} and Bremner, {Ross M} and Tetsuji Takayama and Yulan Cheng and Teodoro Bottiglieri and Nagetaal, {Iris D} and Shrubsole, {Martha J} and Zaidi, {Ali H} and Xin Wang and Coleman, {Helen G} and Anderson, {Lesley A} and Meltzer, {Stephen J} and Ajay Goel and {FINBAR-EMERALD collaborative group}",

note = "{\textcopyright} Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.",

year = "2025",

month = jan,

day = "17",

doi = "10.1136/gutjnl-2024-333364",

language = "English",

volume = "74",

pages = "169--181",

journal = "Gut",

issn = "0017-5749",

publisher = "BMJ Publishing Group",

number = "2",

}

Miyoshi, J, Mannucci, A, Scarpa, M, Gao, F, Toden, S, Whitsett, T, Inge, LJ, Bremner, RM, Takayama, T, Cheng, Y, Bottiglieri, T, Nagetaal, ID, Shrubsole, MJ, Zaidi, AH, Wang, X, Coleman, HG, Anderson, LA, Meltzer, SJ, Goel, A & FINBAR-EMERALD collaborative group 2025, 'Liquid biopsy to identify Barrett’s oesophagus, dysplasia and oesophageal adenocarcinoma: the EMERALD multicentre study', Gut, vol. 74, no. 2, pp. 169-181. https://doi.org/10.1136/gutjnl-2024-333364

TY - JOUR

T1 - Liquid biopsy to identify Barrett’s oesophagus, dysplasia and oesophageal adenocarcinoma: the EMERALD multicentre study

AU - Miyoshi, Jinsei

AU - Mannucci, Alessandro

AU - Scarpa, Marco

AU - Gao, Feng

AU - Toden, Shusuke

AU - Whitsett, Timothy

AU - Inge, Landon J

AU - Bremner, Ross M

AU - Takayama, Tetsuji

AU - Cheng, Yulan

AU - Bottiglieri, Teodoro

AU - Nagetaal, Iris D

AU - Shrubsole, Martha J

AU - Zaidi, Ali H

AU - Wang, Xin

AU - Coleman, Helen G

AU - Anderson, Lesley A

AU - Meltzer, Stephen J

AU - Goel, Ajay

AU - FINBAR-EMERALD collaborative group

PY - 2025/1/17

Y1 - 2025/1/17

N2 - BACKGROUND: There is no clinically relevant serological marker for the early detection of oesophageal adenocarcinoma (EAC) and its precursor lesion, Barrett's oesophagus (BE).OBJECTIVE: To develop and test a blood-based assay for EAC and BE.DESIGN: Oesophageal MicroRNAs of BaRRett, Adenocarcinoma and Dysplasia (EMERALD) was a large, international, multicentre biomarker cohort study involving 792 patient samples from 4 countries (NCT06381583) to develop and validate a circulating miRNA signature for the early detection of EAC and high-risk BE. Tissue-based miRNA sequencing and microarray datasets (n=134) were used to identify candidate miRNAs of diagnostic potential, followed by validation using 42 pairs of matched cancer and normal tissues. The usefulness of the candidate miRNAs was initially assessed using 108 sera (44 EAC, 34 EAC precursors and 30 non-disease controls). We finally trained a machine learning model (XGBoost+AdaBoost) on RT-qPCR results from circulating miRNAs from a training cohort (n=160) and independently tested it in an external cohort (n=295).RESULTS: After a strict process of biomarker discovery and selection, we identified six miRNAs that were overexpressed in all sera of patients compared with non-disease controls from three independent cohorts of different nationalities (miR-106b, miR-146a, miR-15a, miR-18a, miR-21 and miR-93). We established a six-miRNA diagnostic signature using the training cohort (area under the receiver operating characteristic curve (AUROC): 97.6%) and tested it in an independent cohort (AUROC: 91.9%). This assay could also identify patients with BE among patients with gastro-oesophageal reflux disease (AUROC: 94.8%, sensitivity: 92.8%, specificity: 85.1%).CONCLUSION: Using a comprehensive approach integrating unbiased genome-wide biomarker discovery and several independent experimental validations, we have developed and validated a novel blood test that might complement screening options for BE/EAC.TRIAL REGISTRATION NUMBER: NCT06381583

AB - BACKGROUND: There is no clinically relevant serological marker for the early detection of oesophageal adenocarcinoma (EAC) and its precursor lesion, Barrett's oesophagus (BE).OBJECTIVE: To develop and test a blood-based assay for EAC and BE.DESIGN: Oesophageal MicroRNAs of BaRRett, Adenocarcinoma and Dysplasia (EMERALD) was a large, international, multicentre biomarker cohort study involving 792 patient samples from 4 countries (NCT06381583) to develop and validate a circulating miRNA signature for the early detection of EAC and high-risk BE. Tissue-based miRNA sequencing and microarray datasets (n=134) were used to identify candidate miRNAs of diagnostic potential, followed by validation using 42 pairs of matched cancer and normal tissues. The usefulness of the candidate miRNAs was initially assessed using 108 sera (44 EAC, 34 EAC precursors and 30 non-disease controls). We finally trained a machine learning model (XGBoost+AdaBoost) on RT-qPCR results from circulating miRNAs from a training cohort (n=160) and independently tested it in an external cohort (n=295).RESULTS: After a strict process of biomarker discovery and selection, we identified six miRNAs that were overexpressed in all sera of patients compared with non-disease controls from three independent cohorts of different nationalities (miR-106b, miR-146a, miR-15a, miR-18a, miR-21 and miR-93). We established a six-miRNA diagnostic signature using the training cohort (area under the receiver operating characteristic curve (AUROC): 97.6%) and tested it in an independent cohort (AUROC: 91.9%). This assay could also identify patients with BE among patients with gastro-oesophageal reflux disease (AUROC: 94.8%, sensitivity: 92.8%, specificity: 85.1%).CONCLUSION: Using a comprehensive approach integrating unbiased genome-wide biomarker discovery and several independent experimental validations, we have developed and validated a novel blood test that might complement screening options for BE/EAC.TRIAL REGISTRATION NUMBER: NCT06381583

KW - Liquid biopsy

KW - Barrett’s oesophagus

KW - dysplasia

KW - oesophageal adenocarcinoma

U2 - 10.1136/gutjnl-2024-333364

DO - 10.1136/gutjnl-2024-333364

M3 - Article

C2 - 39562048

SN - 0017-5749

VL - 74

SP - 169

EP - 181

JO - Gut

JF - Gut

IS - 2

ER -

Liquid biopsy to identify Barrett’s oesophagus, dysplasia and oesophageal adenocarcinoma: the EMERALD multicentre study

Abstract

Bibliographical note

Publications and Copyright Policy

Keywords

UN SDGs

Access to Document

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