Abstract B075: Detection of early gastric carcinoma by micronuclei DNA from erythrocytes

Abstract Background: Advancements in non-invasive diagnostic technologies for gastric carcinoma (GC), including serum microRNA and cell-free DNA assays, have shown promise but still face challenges in achieving consistent early detection. Micronuclei (MN), extranuclear bodies harboring fragmented chromosomal segments, are indicative of genomic instability and have been employed in genotoxicity assessments and cancer diagnostics. We have developed a novel technique (WO2021/228246 A1) for the purification and characterization of micronuclei DNA (MN-DNA) extracted from erythrocytes in peripheral blood. Here, we evaluated the potential of micronuclei DNA (MN-DNA) from 2ml peripheral blood for early gastric carcinoma detection and explored its application for early cancer diagnosis. Methods: We assembled a clinical cohort consisting of 425 healthy donors (HDs) and 282 gastric cancer patients, from whom 1-2 mL peripheral blood samples were collected. Participants were randomly allocated into training, validation, and independent test cohorts in a 7:2:1 ratio, ensuring similar distributions of cancer stages and gender. MN-DNA was isolated from erythrocytes and subjected to comprehensive whole-genome sequencing. Predictive machine learning models were constructed utilizing distinct tumor-associated MN-DNA features identified through genome-wide analysis to distinguish between HDs and GC. Results: Comprehensive genome-wide analysis of MN-DNA demonstrated pronounced disparities in distribution patterns between HDs and GC patients. The predictive model built on MN-DNA features achieved an AUC of 97.69% (95%CI: 95.57- 99.81%), with an 96.47% specificity and 91.07% sensitivity in the independent test cohort. The model identified early GC (stage 0-I) and advanced GC (stage II-IV) with sensitivities of 95.24% or 78.57%, respectively. Conclusions: Our results demonstrate that MN-DNA from 1-2mL peripheral blood enable accurate detection of GC, especially in early GC. As a type of cytoplasmic DNA, MN-DNA can provide a valuable tool for early cancer detection, offering different underlying mechanisms compared to current methods. Research sponsor: Timing Biotech. Citation Format: Yuehua Han, Xingyun Yao, Haobo Sun, Cheng Fang, Peiwei Li, Honghao Liang, Jie Jin, Xiaofei Gao. Detection of early gastric carcinoma by micronuclei DNA from erythrocytes [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 B075.