Efficacy of cell-free DNA methylation-based blood test for colorectal cancer screening in high-risk population: a prospective cohort study.

Abstract

BACKGROUND:

Although colonoscopy is the standard screening test for colorectal cancer (CRC), its use is limited by a poor compliance rate, the need for extensive bowel preparation, and the risk of complications. As an alternative, an FDA-approved stool-based DNA test, Cologuard, has demonstrated satisfactory detection performance for CRC, but its compliance rate remains suboptimal, primarily attributable to individuals' reluctance to provide stool samples.

METHODS:

We developed a noninvasive blood-based CRC test, ColonSecure, based on cell-free DNA containing cancer-specific CpG island methylation patterns. We initially screened publicly available datasets for differentially methylated CpG sites in CRC with prediction potential. Subsequently, we performed two sequential bisulfite-free methylation sequencing on blood samples obtained from CRC patients and non-cancer controls. Through rigorous evaluation of each marker and machine learning-assisted feature selection, we identified 149 hypermethylated markers from over 193,000 CpG sites. These markers were then utilized to construct the ColonSecure model, enabling accurate CRC detection.

RESULTS:

We validated the efficacy of our cell-free DNA methylation-based blood test for CRC screening with 3493 high-risk individuals identified from 114,136 urban residents. The ColonSecure test identified 89 out of 103 CRC patients diagnosed by the follow-up colonoscopy, outperforming CEA, CRP, and CA19-9 (with a sensitivity of 86.4% compared to 45.6%, 39.8%, and 25.2% for CEA, CRP, and CA19-9 respectively; an AUROC of 0.956 compared to an AUROC of < 0.77 for other methods).

CONCLUSION:

Our observations emphasize the potential of our multiple cfDNA methylation marker-based test for CRC screening in high-risk populations.

• Authors: Fuqiang Zhao, Ping Bai, Jianfeng Xu, Zitong Li, Shan Muhammad, Diange Li, Zeyue Zhang, Yibo Gao, Qian Liu
• Journal: Molecular cancer (Mol Cancer) Vol. 22 Issue 1 Pg. 157 (09 28 2023) ISSN: 1476-4598 [Electronic] England
• PMID: 37770864 (Publication Type: Letter, Research Support, Non-U.S. Gov't)
• Copyright: © 2023. BioMed Central Ltd., part of Springer Nature.

Chemical References

• Cell-Free Nucleic Acids
• CA-19-9 Antigen
• Biomarkers, Tumor

Topics

• Humans
• DNA Methylation
• Cell-Free Nucleic Acids (genetics)
• Prospective Studies
• CA-19-9 Antigen
• Early Detection of Cancer
• CpG Islands
• Colorectal Neoplasms (diagnosis, genetics)
• Biomarkers, Tumor (genetics)