Abstract A045: Evaluating the potential of micronuclei DNA from erythrocytes for early detection of colorectal cancer
Authors: Jiao Yurong , Yao Xingyun , Sun Haobo , Liu Chengcheng , Kong Xiangxing , Liang Honghao , Meng Fei , Li Jun , Ding Kefeng , Gao Xiaofei 
Published: November 2024

Background: Current development in stool- and cell-free DNA (cfDNA)-based technologies have demonstrated promising potentials in colorectal cancer (CRC) diagnosis. However, early detection of CRC and advanced adenoma (AA) remains challenging. Micronuclei (MN) are extranuclear bodies containing chromatin segments resulting from errors in DNA repair. Elevated levels of MN+ erythrocytes have been studied in genotoxicity testing and cancer diagnosis. We further performed whole-genome sequencing on purified and isolated micronuclei DNA (MN-DNA) from erythrocytes in peripheral blood using the approach (WO2021/228246 A1) we previously developed. By comparing MN-DNA from colorectal cancer (CRC) patients and healthy individuals, we identified a series of tumor-associated MN-DNA features (taMN- DNA) with significant differences in read counts and developed a classification model. Here, we established an independent cohort to clinically validate the CRC model and explore its application in early cancer diagnosis. Methods: We launched a prospective observational case- control clinical trial (NCT05875584), which was used as an independent cohort to validate taMN-DNA features in CRC and to perform a comparative analysis with quantitative fecal immunochemical test (qFIT). A total of 598 samples were enrolled in this study (585 was available, including 299 HDs, 206 AAs, and 80 CRCs). We gathered peripheral blood (1-2ml) from a training cohort of 1226 individuals, a test cohort of 309 individuals and this independent cohort of 598 individuals for the MN-DNA isolation from erythrocytes and whole-genome sequencing. Predictive models were developed using distinctive taMN-DNA features identified by genome-wide analysis from training cohort to differentiate between HD and AA or CRC. Results: The predictive CRC model built on taMN-DNA features achieved an AUC of 93% and the detection of AA achieved an AUC of 82% in this clinical validation cohort. Comparing MN-DNA with qFIT, the overall sensitivity was generally consistent (91.3% vs. 87.5%), with MN-DNA achieving 86.4% sensitivity in early-stage (stage I) CRC, significantly higher than 68.2% in qFIT. Additionally, MN-DNA showed superior sensitivity in detecting AA (71.4% vs. 18.4%), with comparable specificity (90.3% vs. 96.3%). Conclusions: Our results demonstrate that MN-DNA within erythrocytes from 1-2ml peripheral blood enable accurate detection of AA and early-stage CRC. Research sponsor: Timing Biotech.

Citation Format: Yurong Jiao, Xingyun Yao, Haobo Sun, Chengcheng Liu, Xiangxing Kong, Honghao Liang, Fei Meng, Jun Li, Kefeng Ding, Xiaofei Gao. Evaluating the potential of micronuclei DNA from erythrocytes for early detection of colorectal cancer [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A045.