Performance of a targeted enzymatic methylation-based early detection test by different colorectal cancer subgroups.

• DOI: 10.1200/jco.2025.43.16_suppl.3596
• Publication Date: 2025-05-28T18:27:53Z
• Authors: Xiaojian Wu; Hong Xu; Zhijian Xu; Nan Lin; Xiaosheng He; Jiandong Tai; Jinlei Song; Min Li; Xiurui Zhu; Fei Zhao; Shiyuan Tong; Yalong Zhang; Ying Xin; Guo Chen; Junyi Ye; Jing Liu; Baoliang Zhu; Xiaohui Wu; Ping Lan

3596 Background: Colorectal cancer (CRC) is the second most frequently diagnosed in China and early detection could prevent over 90% of CRC-related deaths. Blood-based tests that analyze molecular features CRC cell-free DNA (cfDNA), such as methylation fragmentation patterns, hold great promise for detection. However, impact characteristics related to tumor location or mismatch repair (MMR) status on test performance has not been thoroughly investigated. In this study, we developed a blood-based analysed its across different subgroups. Methods: A targeted enzymatic methyl sequencing panel was identify tumor-specific hyper- hypo-methylation markers profiles. case-control cohort 536 participants (268 patients, 268 controls) enrolled startified into training validation sets base case/control stage with 5-fold cross-validation. gradient-boosted tree model built by combining probabilities from methylomic fragmentomic features. The optimal cutoff value determined Youden's index, High specificity sensitivity methods, respectively. Results: overall methods follows: 93.7%, 99.3%, 90.3%, 96.6%, 86.2%, 97.0%, area under curve (AUC) 0.989 (95% CI: 0.981-0.996) , which higher than those current reports. When employing method, sensitivities were comparable between left right-sided colon (86.3% vs 85.7%, p = 1.0), also similar dMMR (deficient repair) pMMR (proficient (87.5% 85.8%, indicating applicable various subtypes. Additionally TNM staging, pathological differentiation status, expression Ki67, are closely aggressiveness, correlated (Table). Conclusions: We have established based ctDNA profiles, shows excellent performance. Notably, newly no significant differences distinct locations varying MMR statuses, suggesting broader applicability types CRC. Subgroup Positive/Total no. Sensitivity p_value Left-sidedRight-sided 195/22636/42 86.3%85.7% 1 7/8200/233 87.5%85.8% Stage IStage II III IV 34/5092/10872/7633/34 68%85.2%94.7%100% ＜0.001 Well differentiated Moderately Poorly 3/3160/19241/42 100%83.3%97.6% 0.029 Ki67_highKi67_low 138/15932/42 86.8%76.2% 0.147