A 5-hydroxymethylcytosine-based non-invasive model for early detection of colorectal carcinomas and advanced adenomas: the METHOD-2 study.
Clin Cancer Res
; 2024 May 30.
Article
em En
| MEDLINE
| ID: mdl-38814264
ABSTRACT
PURPOSE:
Detection of colorectal carcinomas (CRC) at a time when there are more treatment options is associated with better outcomes. This prospective case-control study assessed the 5-hydroxymethylcytosine (5hmC) biomarkers in circulating cell-free DNA (cfDNA) for early detection of CRC and advanced adenomas (AA) ExperimentalDesign:
Plasma cfDNA samples from 2,576 study participants from the multi-center METHOD-2 study (NCT03676075) were collected, comprising patients with newly diagnosed CRC (n=1,074), AA (n=356), other solid tumors (n=80), and non-CRC/AA controls (n=1,066), followed by genome-wide 5hmC profiling using the 5hmC-Seal technique and the next-generation sequencing (NGS). A weighted diagnostic model for CRC (stage I-III) and AA was developed using the elastic net regularization in a discovery set and validated in independent samples.RESULTS:
Distribution of 5hmC in cfDNA reflected gene regulatory relevance and tissue of origin. Besides being confirmed in internal validation, a 96-gene model achieved an area under the curve (AUC) of 90.7% for distinguishing stage I-III CRC from controls in 321 samples from multiple centers for external validation, regardless of primary location or mutation status. This model also showed cancer-type specificity as well as high capacity for distinguishing AA from controls with an AUC of 78.6%. Functionally, differential 5hmC features associated with CRC and AA demonstrated relevance to CRC biology, including pathways such as calcium and MAPK signaling.CONCLUSIONS:
Genome-wide mapping of 5hmC in cfDNA shows the promise as a highly sensitive and specific non-invasive blood test to be integrated in screening programs for improving early detection of CRC and high-risk AA.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Clin Cancer Res
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China