Abstract 5115: A multi-omic liquid biopsy for the earlier detection of colorectal cancer

Abstract Background: Timely diagnosis and intervention in colorectal cancer (CRC) are critical to improving patient outcomes and limiting disease progression. Screening of average-risk individuals is essential for detecting tumors at an earlier, more treatable stage. However, adherence to current screening programs remains suboptimal. Liquid biopsies represent a promising alternative to stool-based tests and may play a key role in optimizing CRC detection and diagnostic pathways. Methods: In this study, 957 patients were recruited across various clinical sites in the USA: 48 CRC, 157 advanced precancerous lesions (APL), 331 non-advanced lesions (NAL) and 421 with a negative colonoscopy diagnosis. Blood was obtained from patients either prior to scheduled colonoscopy or before surgical resection and any anti-cancer therapies. Streck plasma samples were analyzed by the Dxcover® Liquid Biopsy Platform and classified with machine learning algorithms. Results: When CRC was classified against all other groups, the receiver operating characteristic curve generated an area under the curve value of 0.95, and test sensitivity and specificity were 90% and 89%, respectively. The diagnostic model accurately predicted 75% of stage I (3/4), 100% of stage II (15/15), 93% of stage III (14/15) and 100% of stage IV (6/6) CRCs. For the advanced colorectal neoplasia model, 29% of APL were detected. Conclusion: A simple blood test with high sensitivity for early-stage colorectal cancer could significantly enhance patient outcomes. With continued development, this liquid biopsy has the potential to make a substantial impact on the early detection of CRC. Citation Format: James M. Cameron, Holly J. Butler, David S. Palmer, Rose G. McHardy, Alexandra Sala, Matthew J. Baker. A multi-omic liquid biopsy for the earlier detection of colorectal cancer abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 5115.