Central Laboratory & Shenzhen Key Laboratory of Epigenetics and Precision Medicine for Cancers, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, 518116, China.
Laboratory of Translational Medicine, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
Mol Cancer. 2024 Aug 22;23(1):173. doi: 10.1186/s12943-024-01959-3.
Early detection of colorectal cancer (CRC) significantly enhances patient outcomes. Conventional CRC screening tools, like endoscopy and stool-based tests, have constraints due to their invasiveness or suboptimal patient adherence. Recently, liquid biopsy employing plasma cell-free DNA (cfDNA) has emerged as a potential noninvasive screening technique for various malignancies.
In this research, we harnessed the Mutation Capsule Plus (MCP) technology to profile an array of genomic characteristics from cfDNA procured from a single blood draw. This profiling encompassed DNA methylation, the 5' end motif, copy number variation (CNV), and genetic mutations. An integrated model built upon selected multiomics biomarkers was trained using a cohort of 93 CRC patients and 96 healthy controls.
This model was subsequently validated in another cohort comprising 89 CRC patients and 95 healthy controls. Remarkably, the model achieved an area under the curve (AUC) of 0.981 (95% confidence interval (CI), 0.965-0.998) in the validation set, boasting a sensitivity of 92.1% (95% CI, 84.5%-96.8%) and a specificity of 94.7% (95% CI, 88.1%-98.3%). These numbers surpassed the performance of any single genomic feature. Importantly, the sensitivities reached 80% for stage I, 89.2% for stage II, and were 100% for stages III and IV.
Our findings underscore the clinical potential of our multiomics liquid biopsy test, indicating its prospective role as a noninvasive method for early-stage CRC detection. This multiomics approach holds promise for further refinement and broader clinical application.
早期发现结直肠癌（CRC）可显著改善患者的预后。传统的 CRC 筛查工具，如内窥镜和粪便检测，由于其侵入性或患者依从性不佳而存在局限性。最近，利用血浆无细胞 DNA（cfDNA）的液体活检已成为各种恶性肿瘤潜在的非侵入性筛查技术。
在这项研究中，我们利用 Mutation Capsule Plus（MCP）技术从单次采血获得的 cfDNA 中分析一系列基因组特征。该分析包括 DNA 甲基化、5'端基序、拷贝数变异（CNV）和基因突变。基于选定的多组学生物标志物构建的综合模型，使用 93 例 CRC 患者和 96 例健康对照者的队列进行了训练。
该模型随后在另一组包括 89 例 CRC 患者和 95 例健康对照者的队列中进行了验证。值得注意的是，该模型在验证组中的曲线下面积（AUC）为 0.981（95%置信区间（CI），0.965-0.998），灵敏度为 92.1%（95%CI，84.5%-96.8%），特异性为 94.7%（95%CI，88.1%-98.3%）。这些数字超过了任何单一基因组特征的性能。重要的是，I 期的灵敏度达到 80%，II 期达到 89.2%，III 期和 IV 期达到 100%。
我们的研究结果强调了我们的多组学生物液体活检测试的临床潜力，表明其作为早期 CRC 检测的非侵入性方法具有潜在的应用前景。这种多组学方法有望进一步完善和更广泛的临床应用。
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