结直肠癌 (CRC) 的早期检测可显着改善患者的治疗效果。传统的结直肠癌筛查工具，如内窥镜检查和粪便检测，由于其侵入性或患者依从性不佳而受到限制。最近，采用血浆游离 DNA (cfDNA) 的液体活检已成为一种针对各种恶性肿瘤的潜在无创筛查技术。在这项研究中，我们利用 Mutation Capsule Plus (MCP) 技术来分析从以下来源获得的 cfDNA 的一系列基因组特征：一次抽血。该分析涵盖 DNA 甲基化、5' 末端基序、拷贝数变异 (CNV) 和基因突变。使用由 93 名 CRC 患者和 96 名健康对照组成的队列训练基于选定的多组学生物标志物构建的集成模型。该模型随后在由 89 名 CRC 患者和 95 名健康对照组成的另一个队列中得到验证。值得注意的是，该模型在验证集中的曲线下面积 (AUC) 为 0.981（95% 置信区间 (CI)，0.965-0.998），灵敏度高达 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 期的敏感性达到 80%，II 期的敏感性达到 89.2%，III 期和 IV 期的敏感性为 100%。我们的研究结果强调了我们的多组学液体活检测试的临床潜力，表明其作为早期诊断的非侵入性方法的前瞻性作用。 -阶段CRC检测。这种多组学方法有望进一步完善和更广泛的临床应用。© 2024。作者。

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.© 2024. The Author(s).