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][1]) 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][1]. Data sharing not applicable as no datasets generated and/or analysed for this study. Data collected for the study, including deidentified participant data and the code, will be made available to others at publication via a signed data access agreement and at the discretion of the investigators’ approval of the proposed use of such data. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT06381583&atom=%2Fgutjnl%2Fearly%2F2024%2F11%2F18%2Fgutjnl-2024-333364.atom

中文翻译：

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液体活检识别 Barrett 食管、异型增生和食管腺癌：EMERALD 多中心研究


背景 没有临床相关的血清学标志物可用于早期检测食管腺癌 （EAC） 及其前体病变巴雷特食管 （BE）。目的 开发和测试基于血液的 EAC 和 BE 检测方法。设计 BaRRett、腺癌和异型增生的食管 MicroRNA （EMERALD） 是一项大型、国际、多中心生物标志物队列研究，涉及来自 4 个国家的 792 名患者样本 （[NCT06381583][1]），以开发和验证用于早期检测 EAC 和高危 BE 的循环 miRNA 特征。基于组织的 miRNA 测序和微阵列数据集 （n=134） 用于鉴定具有诊断潜力的候选 miRNA，然后使用 42 对匹配的癌症和正常组织进行验证。最初使用 108 份血清（44 份 EAC、34 份 EAC 前体和 30 份非疾病对照）评估候选 miRNA 的有用性。最后，我们在来自训练队列 （n=160） 的循环 miRNA 的 RT-qPCR 结果上训练了一个机器学习模型 （XGBoost+AdaBoost），并在外部队列 （n=295） 中独立测试了它。结果 经过严格的生物标志物发现和筛选过程，与非疾病对照相比，我们从 3 个不同国籍的独立队列 （miR-106b、miR-146a、miR-15a、miR-18a、miR-21 和 miR-93） 中鉴定出 6 个在患者所有血清中过表达的 miRNA。我们使用训练队列 （受试者工作特征曲线下面积 （AUROC） ： 97.6%） 建立了 6-miRNA 诊断特征，并在独立队列 （AUROC： 91.9%） 中对其进行了测试。该检测还可以在胃食管反流病患者中识别 BE 患者 （AUROC： 94.8%，敏感性： 92.8%，特异性： 85.1%）。 结论 使用整合无偏倚全基因组生物标志物发现和几个独立实验验证的综合方法，我们开发并验证了一种新型血液测试，可能补充 BE/EAC 的筛查选项。试验注册号 [NCT06381583][1]。数据共享不适用，因为没有为本研究生成和/或分析数据集。为研究收集的数据，包括去标识化的参与者数据和代码，将在发布时通过签署的数据访问协议提供给其他人，并由研究者批准此类数据的拟议用途自行决定。[1]： /lookup/external-ref？link_type=CLINTRIALGOV&access_num=NCT06381583&atom=%2Fgutjnl%2Fearly%2F2024%2F11%2F18%2Fgutjnl-2024-333364.原子