Hu Wenzhe, Zhao Xudong, Luo Nan, Xiao Mengmeng, Feng Feng, An Yuan, Chen Jianfei, Rong Long, Yang Yinmo, Peng Jirun
Department of Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
School of Oncology, Capital Medical University, Beijing, China.
Front Oncol. 2025 Mar 10;15:1552426. doi: 10.3389/fonc.2025.1552426. eCollection 2025.
Aberrant 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.
We 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.
We identified a total of 120 cfDNA methylation biomarkers, including , , and , 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.
Our study identified cfDNA methylation markers for PAC, offering a novel approach for the early, noninvasive diagnosis of PAC.
基因组DNA CpG岛（CGIs）的异常高甲基化在人类胰腺癌（PAC）中经常被观察到。血浆游离DNA（cfDNA）甲基化分析方法可用于PAC的早期和非侵入性检测。本研究还旨在将PAC与其他癌症类型区分开来。
我们采用甲基化CpG串联扩增和测序（MCTA-Seq）方法，该方法针对约三分之一的CGIs，对PAC患者（n = 50）和健康对照（n = 52）以及癌组织和癌旁非癌组织样本（n = 66）的血浆样本进行检测。评估了该方法在检测PAC以及将其与肝细胞癌（HCC）、结直肠癌（CRC）和胃癌（GC）区分开来方面的有效性。此外，还建立了PAC的甲基化评分和分型系统。
我们总共鉴定出120个cfDNA甲基化生物标志物，包括 、 和 ，用于血液中PAC的检测。包含这些生物标志物的检测组在发现队列和验证队列中的患者中分别达到了97%和86%的灵敏度，在两个队列中的特异性均为100%。甲基化评分和分型系统具有临床适用性。此外，我们还鉴定出PAC与HCC、CRC和GC之间数百个差异甲基化的cfDNA生物标志物。这些标志物的某些组合可用于一种高度特异性（约100%）的算法，以在血液中区分PAC与HCC、CRC和GC。
我们的研究鉴定出了PAC的cfDNA甲基化标志物，为PAC的早期非侵入性诊断提供了一种新方法。
