Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai, China.
Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
BMC Med. 2024 Oct 8;22(1):436. doi: 10.1186/s12916-024-03662-y.
A blood-based diagnostic test is a promising strategy for colorectal cancer (CRC). The MethyDT test (IColohunter), which detects methylation levels of NTMT1 and MAP3K14-AS1, exhibited potential in discriminating CRC, but its clinical performance needs to be validated in large-scale populations.
A multicenter, double-blinded, cross-sectional study that enrolled 1194 participants was performed. Plasma samples were collected to detect methylation levels of NTMT1 and MAP3K14-AS1 using quantitative methylation-specific PCR with the MethyDT test, and the accuracy was further evaluated by Sanger sequencing.
The sensitivities of the MethyDT test for detecting CRC, early stages of CRC (I and II), advanced adenoma (AA), and high-grade intraepithelial neoplasia (HGIN) were 91.2% (95% confidence interval [CI], 88.4-94.0), 87.4% (95% CI, 82.5-92.2), 43.5% (95% CI, 35.7-51.4), and 72.7% (95% CI, 57.5-87.9), respectively. The specificities for participants with non-AA, interfering diseases (ID), and no evidence of disease (NED) were 85.0% (95% CI, 78.8-91.3), 93.7% (95% CI, 91.4-95.9) and 97.3% (95% CI, 90.5-99.7), respectively, and its overall specificity for all-controls was 92.4% (95% CI, 90.3-94.4). The consistency of the MethyDT test with pathology for CRC was high with a kappa value of 0.830 (95% CI, 0.795-0.865). Additionally, the MethyDT test was comparable to Sanger sequencing for detecting methylation with kappa values > 0.97.
The MethyDT test demonstrates excellent sensitivity and specificity for CRC and high consistency with Sanger sequencing for methylation, suggesting it may serve as a potential noninvasive diagnostic tool for the detection of CRC.
This clinical trial has been registered in ClinicalTrials.gov (NCT05508503).
基于血液的诊断测试是结直肠癌（CRC）的一种有前途的策略。MethyDT 测试（Icolohunter）检测 NTMT1 和 MAP3K14-AS1 的甲基化水平，在区分 CRC 方面表现出潜力，但需要在大规模人群中验证其临床性能。
进行了一项多中心、双盲、前瞻性研究，共纳入 1194 名参与者。采集血浆样本，采用定量甲基化特异性 PCR 法检测 MethyDT 试验中 NTMT1 和 MAP3K14-AS1 的甲基化水平，并通过 Sanger 测序进一步评估准确性。
MethyDT 试验检测 CRC、CRC 早期（I 和 II 期）、高级腺瘤（AA）和高级上皮内瘤变（HGIN）的灵敏度分别为 91.2%（95%置信区间[CI]，88.4-94.0）、87.4%（95% CI，82.5-92.2）、43.5%（95% CI，35.7-51.4）和 72.7%（95% CI，57.5-87.9）。非 AA、干扰性疾病（ID）和无疾病证据（NED）参与者的特异性分别为 85.0%（95% CI，78.8-91.3）、93.7%（95% CI，91.4-95.9）和 97.3%（95% CI，90.5-99.7），总体特异性为 92.4%（95% CI，90.3-94.4）。MethyDT 试验与病理学对 CRC 的一致性较高，kappa 值为 0.830（95% CI，0.795-0.865）。此外，MethyDT 试验与 Sanger 测序检测甲基化的kappa 值>0.97相当。
MethyDT 试验对 CRC 具有出色的灵敏度和特异性，与 Sanger 测序的甲基化具有高度一致性，表明它可能成为 CRC 检测的一种潜在非侵入性诊断工具。
本临床试验已在 ClinicalTrials.gov 注册（NCT05508503）。
