Abstract A041: Detection of early-stage gastrointestinal cancers using micronuclei DNA from erythrocytes
Authors: Sun Haobo , Yao Xingyun , Han Yuehua , Jiao Yurong , Kong Xiangxing , Liu Chengcheng , Guo Qingqu , Meng Fei , Liang Honghao , Li Hongbo , Fan Xiuqin , Li Jun , Gao Xiaofei 
Published: November 2024

Background: Gastrointestinal (GI) cancers account for over a third of cancer deaths. However, their early detection remains a challenge. Micronuclei (MN) are cytoplasm-resident subcellular structures, containing damaged chromosome segments that indicative of genomic instability. Increased MN frequency in hematopoietic cells is observed in patients with solid tumors. Our developed technique (WO2021/228246 A1) enables the purification and characterization of micronuclei DNA in erythrocytes from peripheral blood. By comparing MN-DNA from healthy donors (HDs) and GI cancer patients, we identified significant changes in read densities at specific genomic locations in patients, which were termed as tumor-associated MN-DNA (taMN- DNA) features. Here, we evaluated the potential of these features for early-stage GI cancer detection, including colorectal (CC), gastric (GC) and esophageal (EC) cancers. Methods: Peripheral blood (1-2 mL) was collected from healthy donors (HD) and cancer patients MN-DNA isolation and purification from erythrocytes. Participants were randomly divided into training, validation and independent test cohorts in a 7:2:1 ratio, maintaining similar cancer types, gender and age distribution. Distinct MN-DNA features between cancer patients and HDs were identified using sequencing data. Machine learning algorithms were applied using these features for cancer detection. Results: The study enrolled 1753 participants, including 987 HDs, 420 CC, 282 GC and 64 EC cases. Of these, over half were diagnosed with early-stage diseases; TNM stage 0-I accounted for 40.57%, stage II for 23.32%, stage III for 29.25% and stage IV for 6.87%. The pan-cancer model achieved 88.2% sensitivity with an overall specificity of 95.4%. Patients in individual caner types were detected from the tissue of origin classification with an overall accuracy of 91.9% based on pan-cancer at 95.4% specificity. Sensitivity was 90.8% for CC, 91.7% for GC and 100% for EC. For early- stage (stage 0-II) CC, GC and EC, the model demonstrated sensitivities of 97.4%, 94.7% and 100.00%, respectively, at 95.4% specificity. Conclusions: Unlike cell-free DNA, MN-DNA are chromosomal fragments in the cytoplasm. The abundance of erythrocytes in peripheral blood provides an easily accessible source for MN-DNA enrichment. This pilot study illustrates the potential of MN-DNA as a tool for early GI cancer detection, contributing to large-scale efforts towards developing an effective GI cancer screening test. Research sponsor: Timing Biotech.

Citation Format: Haobo Sun, Xingyun Yao, Yuehua Han, Yurong Jiao, Xiangxing Kong, Chengcheng Liu, Qingqu Guo, Fei Meng, Honghao Liang, Hongbo Li, Xiuqin Fan, Jun Li, Xiaofei Gao. Detection of early-stage gastrointestinal cancers using 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 A041.