Miyoshi Jinsei, Mannucci Alessandro, Scarpa Marco, Gao Feng, Toden Shusuke, Whitsett Timothy, Inge Landon J, Bremner Ross M, Takayama Tetsuji, Cheng Yulan, Bottiglieri Teodoro, Nagtegaal Iris D, Shrubsole Martha J, Zaidi Ali H, Wang Xin, Coleman Helen G, Anderson Lesley A, Meltzer Stephen J, Goel Ajay
Center for Gastrointestinal Research; Center from Translational Genomics and Oncology, Baylor Scott & White Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA.
Department of Gastroenterology and Oncology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.
Gut. 2025 Jan 17;74(2):169-181. doi: 10.1136/gutjnl-2024-333364.
There is no clinically relevant serological marker for the early detection of oesophageal adenocarcinoma (EAC) and its precursor lesion, Barrett's oesophagus (BE).
To develop and test a blood-based assay for EAC and BE.
Oesophageal MicroRNAs of BaRRett, Adenocarcinoma and Dysplasia () 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).
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%).
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.
NCT06381583.
目前尚无用于早期检测食管腺癌（EAC）及其前驱病变巴雷特食管（BE）的具有临床相关性的血清学标志物。
开发并测试一种针对EAC和BE的血液检测方法。
巴雷特食管、腺癌和发育异常的食管微小RNA（Oesophageal MicroRNAs of BaRRett, Adenocarcinoma and Dysplasia，OMRADD）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份患者样本（NCT06381583），旨在开发并验证一种用于早期检测EAC和高危BE的循环微小RNA特征。基于组织的微小RNA测序和微阵列数据集（n = 134）用于识别具有诊断潜力的候选微小RNA，随后使用42对匹配的癌组织和正常组织进行验证。候选微小RNA的有效性最初使用108份血清进行评估（44例EAC、34例EAC前驱病变和30例非疾病对照）。我们最终在来自训练队列（n = 160）的循环微小RNA的逆转录定量聚合酶链反应（RT-qPCR）结果上训练了一个机器学习模型（XGBoost+AdaBoost），并在一个外部队列（n = 295）中进行独立测试。
经过严格的生物标志物发现和选择过程，我们鉴定出六种微小RNA，与来自三个不同国籍独立队列的非疾病对照相比，这些微小RNA在所有患者血清中均过度表达（miR-106b、miR-146a、miR-15a、miR-18a、miR-21和miR-93）。我们使用训练队列建立了一种六微小RNA诊断特征（受试者操作特征曲线下面积（AUROC）：97.6%），并在一个独立队列中进行测试（AUROC：91.9%）。该检测方法还可以在胃食管反流病患者中识别出BE患者（AUROC：94.8%，敏感性：92.8%，特异性：85.1%）。
通过整合无偏全基因组生物标志物发现和多项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检测方法，该方法可能补充BE/EAC的筛查选择。
NCT06381583。
