Integration of multiomics features for blood-based early detection of colorectal cancer

作者：Yibo Gao, Dandan Cao, Mengfan Li, Fuqiang Zhao, Pei Wang, Shiwen Mei, Qianqian Song, Pei Wang, Yanli Nie, Wei Zhao, Sizhen Wang, Hai Yan, Xishan Wang, Yuchen Jiao, Qian Liu · 发表于：Molecular Cancer · 年份：2024 · DOI：10.1186/s12943-024-01959-3 · 被引用次数：35 · 研究领域：Cancer Genomics and Diagnostics、Colorectal Cancer Screening and Detection、Genetic factors in colorectal cancer

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Our findings underscore the clinical potential of our multiomics liquid biopsy test, indicating its prospective role as a noninvasi...