Abstract 4597: 5-Hydroxymethylcytosine signatures in cell-free DNA as a potential biomarker for colorectal cancer andprecancerous adenoma

Colorectal cancer (CRC) is a serious malignancy with the third incidence and second mortality throughout the world. 5-Hydroxymethylcytosine (5hmC) signatures in circulating cell-free DNA (cfDNA) is an important epigenetic mark linked with human cancer pathogenesis. Here we explored the genome-wide 5-hydroxymethylcytosine profiling in the plasma cfDNA and tissue genomic DNA (gDNA) acquired from 101 samples (63 from plasma and 38 from tissues), collected from 21 CRC patients, 21 precancerous adenoma (AD) patients and 21 healthy control individuals (HC). 5hmC modifications exhibited distinct features in promoter and gene body regions in all 5 groups (3 groups from plasma and 2 groups from tissues), which offered a global overview of epigenetic changes of colon pathogenic statuses between early stage CRC and AD. Adenoma showed an independent property in the 5hmC profiles compared to cancer and healthy control. The 5hmC signatures in tumor were more comprehensive and could be divided into two clusters, one was similar to the healthy individuals and the other was similar to the AD patients. The results indicated that the candidate biomarkers to distinguish colorectal cancer from the blood-test population should be generated in two ways, one focused on the differential 5hmC features between CRC patients and healthy individuals; the other should detect the adenoma and tumor patients more extensive according to their precise pathological diagnosis and clinical information. Candidate cfDNA 5hmC biomarkers were further identified in the differential 5hmC modification regions between CRC and HC with a higher sensitivity than the classical CEA marker in non-invasive blood-based diagnosis. We suggested that the differentially enriched 5hmC regions in cfDNA were potential biomarkers to track colorectal cancer, even precancerous adenoma, with further large-scale follow-up studies. Citation Format: Zewen Xiao, Jiayan Wu, Chunlong Wu, Man Li, Fuming Sun, Lu Zheng, Gaojing Liu, Xiaoling Li, Zhiyuan Yun, Jiebing Tang, Yang Yu, Shengnan Luo, Wenji Sun, Xiaohong Feng, Qian Cheng, Xue Tao, Jian Bai, Lin Wu, Shuangxiu Wu, Ji Tao. 5-Hydroxymethylcytosine signatures in cell-free DNA as a potential biomarker for colorectal cancer andprecancerous adenoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4597.