Non-invasive diagnosis of esophageal cancer by a simplified circulating cell-free DNA methylation assay targeting OTOP2 and KCNA3: a double-blinded, multicenter, prospective study.

IF 29.5 1区 医学 Q1 HEMATOLOGY Journal of Hematology & Oncology Pub Date : 2024-06-18 DOI:10.1186/s13045-024-01565-2
Yan Bian, Ye Gao, Han Lin, Chang Sun, Wei Wang, Siyu Sun, Xiuling Li, Zhijie Feng, Jianlin Ren, Hezhong Chen, Chaojing Lu, Jinfang Xu, Jun Zhou, Kangkang Wan, Lei Xin, Zhaoshen Li, Luowei Wang
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Abstract

Background: Esophageal cancer (EC) is a highly lethal disease lacking early detection approaches. We previously identified that OTOP2 and KCNA3 were specifically hypermethylated in circulating cell-free DNA from patients with EC. We then developed a blood-based methylation assay targeting OTOP2 and KCNA3 (named "IEsohunter") for esophageal cancer noninvasive detection. This double-blinded, multicenter, prospective study aimed to comprehensively evaluate its clinical diagnostic performance.

Methods: Participants with EC, high-grade intraepithelial neoplasia (HGIN), other malignancies, benign gastrointestinal lesions, or no abnormalities were prospectively enrolled from 5 tertiary referral centers across China. Peripheral blood samples were collected, followed by plasma cell-free DNA methylation analysis using the IEsohunter test based on multiplex quantitative polymerase chain reaction adopting an algorithm-free interpretation strategy. The primary outcome was the diagnostic accuracy of IEsohunter test for EC.

Results: We prospectively enrolled 1116 participants, including 334 patients with EC, 71 with HGIN, and 711 controls. The areas under the receiver operating characteristic curves of the IEsohunter test for detecting EC and HGIN were 0.903 (95% CI 0.880-0.927) and 0.727 (95% CI 0.653-0.801), respectively. IEsohunter test showed sensitivities of 78.5% (95% CI 69.1-85.6), 87.3% (95% CI 79.4-92.4), 92.5% (95% CI 85.9-96.2), and 96.9% (95% CI 84.3-99.8) for stage I-IV EC, respectively, with an overall sensitivity of 87.4% (95% CI 83.4-90.6) and specificity of 93.3% (95% CI 91.2-94.9) for EC detection. The IEsohunter test status turned negative (100.0%, 47/47) after surgical resection of EC.

Conclusions: The IEsohunter test showed high diagnostic accuracy for EC detection, indicating that it could potentially serve as a tool for noninvasive early detection and surveillance of EC.

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以 OTOP2 和 KCNA3 为靶点的简化循环无细胞 DNA 甲基化检测法对食管癌的无创诊断:一项双盲、多中心、前瞻性研究。
背景:食管癌(EC)是一种致死率极高的疾病,缺乏早期检测方法。我们之前发现,在食管癌患者的循环无细胞 DNA 中,OTOP2 和 KCNA3 存在特异性高甲基化。随后,我们开发了一种针对 OTOP2 和 KCNA3 的血液甲基化检测方法(命名为 "IEsohunter"),用于食管癌的无创检测。这项双盲、多中心、前瞻性研究旨在全面评估其临床诊断性能:方法: 前瞻性地从全国 5 家三级转诊中心招募了患有食管癌、高级别上皮内瘤变(HGIN)、其他恶性肿瘤、良性胃肠道病变或无异常的参与者。采集外周血样本,然后使用基于多重定量聚合酶链反应的 IEsohunter 检验进行血浆细胞无 DNA 甲基化分析,该检验采用无算法解释策略。主要结果是IEsohunter检测对EC的诊断准确性:我们前瞻性地招募了1116名参与者,其中包括334名EC患者、71名HGIN患者和711名对照者。IEsohunter检验检测EC和HGIN的接收器操作特征曲线下面积分别为0.903(95% CI 0.880-0.927)和0.727(95% CI 0.653-0.801)。IEsohunter检测对I-IV期EC的敏感性分别为78.5%(95% CI 69.1-85.6)、87.3%(95% CI 79.4-92.4)、92.5%(95% CI 85.9-96.2)和96.9%(95% CI 84.3-99.8),EC检测的总体敏感性为87.4%(95% CI 83.4-90.6),特异性为93.3%(95% CI 91.2-94.9)。手术切除EC后,IEsohunter检测结果转为阴性(100.0%,47/47):结论:IEsohunter检测对EC检测的诊断准确率很高,表明它有可能成为EC无创早期检测和监测的工具。
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来源期刊
CiteScore
48.10
自引率
2.10%
发文量
169
审稿时长
6-12 weeks
期刊介绍: The Journal of Hematology & Oncology, an open-access journal, publishes high-quality research covering all aspects of hematology and oncology, including reviews and research highlights on "hot topics" by leading experts. Given the close relationship and rapid evolution of hematology and oncology, the journal aims to meet the demand for a dedicated platform for publishing discoveries from both fields. It serves as an international platform for sharing laboratory and clinical findings among laboratory scientists, physician scientists, hematologists, and oncologists in an open-access format. With a rapid turnaround time from submission to publication, the journal facilitates real-time sharing of knowledge and new successes.
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