Mutation-Agnostic Detection of Colorectal Cancer Using Liquid Biopsy-Based Methylation-Specific Signatures

Authors

Mohamed A Gouda
Dzifa Y Duose
Morten Lapin
Stephanie Zalles
Helen J Huang
Yuanxin Xi
Xiaofeng Zheng
Amira I Aldesoky
Alshimaa M Alhanafy
Mohamed A Shehata
Jing Wang
Scott Kopetz
Funda Meric-Bernstam
Ignacio I Wistuba
Rajyalakshmi Luthra
Filip Janku

Publication Date

4-6-2023

Journal

The Oncologist

Abstract

Detection of methylation patterns in circulating tumor DNA (ctDNA) can offer a novel approach for cancer diagnostics given the unique signature for each tumor type. We developed a next-generation sequencing (NGS)-based assay targeting 32 CpG sites to detect colorectal cancer-specific ctDNA. NGS was performed on bisulfite-converted libraries and status dichotomization was done using median methylation ratios at all targets. We included plasma samples from patients with metastatic colorectal (n = 20) and non-colorectal cancers (n = 8); and healthy volunteers (n = 4). Median methylation ratio was higher in colorectal cancer compared with non-colorectal cancers (P = .001) and normal donors (P = .005). The assay detected ctDNA in 85% of patients with colorectal cancer at a specificity of 92%. Notably, we were able to detect methylated ctDNA in 75% of patients in whom ctDNA was not detected by other methods. Detection of methylated ctDNA was associated with shorter median progression-free survival compared to non-detection (8 weeks versus 54 weeks; P = .027).

Keywords

Humans, Methylation, Neoplasms, Circulating Tumor DNA, Liquid Biopsy, Mutation, Biomarkers, Tumor, Colorectal Neoplasms, circulating tumor DNA, colorectal cancer, liquid biopsy, methylation

DOI

10.1093/oncolo/oyac204

PMID

36200910

PMCID

PMC10078907

PubMedCentral® Posted Date

10-6-2022

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes