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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.
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.
摘要：
背景：食管癌（EC）是一种高度致命的疾病，缺乏早期检测方法。我们先前确定OTOP2和KCNA3在来自EC患者的循环无细胞DNA中被特异性超甲基化。然后，我们开发了一种针对OTOP2和KCNA3的基于血液的甲基化检测方法（名为“IEsohunter”），用于食管癌的非侵入性检测。这个双盲，多中心，前瞻性研究旨在全面评估其临床诊断性能。
方法：EC的参与者，高级别上皮内瘤变（HGIN），其他恶性肿瘤,良性胃肠道病变,前瞻性纳入了来自中国5个三级转诊中心的异常或无异常.收集外周血样本，然后使用基于多重定量聚合酶链反应的IEsohunter测试，采用无算法解释策略进行血浆无细胞DNA甲基化分析。主要结果是IEsohunter测试对EC的诊断准确性。
结果：我们前瞻性招募了1116名参与者，包括334例EC患者，71与HGIN，和711控制。用于检测EC和HGIN的IEsohunter测试的接收器工作特征曲线下面积为0.903（95％CI0.880-0.927）和0.727（95％CI0.653-0.801），分别。IEsohunter测试显示敏感性为78.5%(95%CI69.1-85.6)，87.3%（95%CI79.4-92.4），92.5%（95%CI85.9-96.2），I-IV期EC为96.9%（95%CI84.3-99.8），分别,EC检测的总体灵敏度为87.4%（95%CI83.4-90.6），特异性为93.3%（95%CI91.2-94.9）。IEsohunter测试状态变为阴性(100.0%，47/47）手术切除EC后。
结论：IEsohunter测试对EC检测显示出较高的诊断准确性，这表明它可能作为一种非侵入性早期检测和监测EC的工具。
方法：EC的参与者，高级别上皮内瘤变（HGIN），其他恶性肿瘤,良性胃肠道病变,前瞻性纳入了来自中国5个三级转诊中心的异常或无异常.收集外周血样本，然后使用基于多重定量聚合酶链反应的IEsohunter测试，采用无算法解释策略进行血浆无细胞DNA甲基化分析。主要结果是IEsohunter测试对EC的诊断准确性。
结果：我们前瞻性招募了1116名参与者，包括334例EC患者，71与HGIN，和711控制。用于检测EC和HGIN的IEsohunter测试的接收器工作特征曲线下面积为0.903（95％CI0.880-0.927）和0.727（95％CI0.653-0.801），分别。IEsohunter测试显示敏感性为78.5%(95%CI69.1-85.6)，87.3%（95%CI79.4-92.4），92.5%（95%CI85.9-96.2），I-IV期EC为96.9%（95%CI84.3-99.8），分别,EC检测的总体灵敏度为87.4%（95%CI83.4-90.6），特异性为93.3%（95%CI91.2-94.9）。IEsohunter测试状态变为阴性(100.0%，47/47）手术切除EC后。
结论：IEsohunter测试对EC检测显示出较高的诊断准确性，这表明它可能作为一种非侵入性早期检测和监测EC的工具。
