Circulating cell-free DNA methylation analysis of pancreatic cancer patients for early noninvasive diagnosis

Bibliographic Details
Title: Circulating cell-free DNA methylation analysis of pancreatic cancer patients for early noninvasive diagnosis
Authors: Wenzhe Hu, Xudong Zhao, Nan Luo, Mengmeng Xiao, Feng Feng, Yuan An, Jianfei Chen, Long Rong, Yinmo Yang, Jirun Peng
Source: Frontiers in Oncology, Vol 15 (2025)
Publisher Information: Frontiers Media S.A., 2025.
Publication Year: 2025
Collection: LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Subject Terms: circulating cell-free DNA, DNA methylation, pancreatic cancer, early noninvasive diagnosis, hepatocellular carcinoma, colorectal cancer, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
More Details: BackgroundAberrant hypermethylation of genomic DNA CpG islands (CGIs) is frequently observed in human pancreatic cancer (PAC). A plasma cell-free DNA (cfDNA) methylation analysis method can be utilized for the early and noninvasive detection of PAC. This study also aimed to differentiate PAC from other cancer types.MethodsWe employed the methylated CpG tandem amplification and sequencing (MCTA-Seq) method, which targets approximately one-third of CGIs, on plasma samples from PAC patients (n = 50) and healthy controls (n = 52), as well as from cancerous and adjacent noncancerous tissue samples (n = 66). The method’s efficacy in detecting PAC and distinguishing it from hepatocellular carcinoma (HCC), colorectal cancer (CRC), and gastric cancer (GC) was evaluated. Additionally, a methylation score and typing system for PAC was also established.ResultsWe identified a total of 120 cfDNA methylation biomarkers, including IRX4, KCNS2, and RIMS4, for the detection of PAC in blood. A panel comprising these biomarkers achieved a sensitivity of 97% and 86% for patients in the discovery and validation cohorts, respectively, with a specificity of 100% in both cohorts. The methylation scoring and typing systems were clinically applicable. Furthermore, we identified hundreds of differentially methylated cfDNA biomarkers between PAC and HCC, CRC, and GC. Certain combinations of these markers can be used in a highly specific (approximately 100%) algorithm to differentiate PAC from HCC, CRC, and GC in blood.ConclusionsOur study identified cfDNA methylation markers for PAC, offering a novel approach for the early, noninvasive diagnosis of PAC.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2234-943X
Relation: https://www.frontiersin.org/articles/10.3389/fonc.2025.1552426/full; https://doaj.org/toc/2234-943X
DOI: 10.3389/fonc.2025.1552426
Access URL: https://doaj.org/article/c9cd107113214cf994e37263e5d675b8
Accession Number: edsdoj.9cd107113214cf994e37263e5d675b8
Database: Directory of Open Access Journals
More Details
ISSN:2234943X
DOI:10.3389/fonc.2025.1552426
Published in:Frontiers in Oncology
Language:English