ORIGINAL RESEARCH article

Front. Immunol.

Sec. Cancer Immunity and Immunotherapy

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1607548

This article is part of the Research Topicm6A Methylation and Cancer ImmunityView all 4 articles

Combining the DNA methylation markers of circulating tumor cells with immune infiltrating cells to assess recurrence and prognosis and to suggest a therapeutic strategy in Stage III-IV colorectal cancer

Provisionally accepted
Yuansen LiYuansen Li1Juan ZhouJuan Zhou1Danli YeDanli Ye1Xuwen LaiXuwen Lai1Wenzhi CuiWenzhi Cui1WENYUAN HEWENYUAN HE1Ling YuLing Yu1Jingyi WuJingyi Wu2Guangning YanGuangning Yan1Chengyong LeiChengyong Lei3Wang WeiWang Wei1,4*
  • 1General Hospital of Southern Theater Command of the Chinese People's Liberation Army, Guangzhou, China
  • 2Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China
  • 3Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China
  • 4Southern Medical University, Guangzhou, Guangdong, China

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Circulating tumor DNA (ctDNA) methylation markers hold promise for detecting cancer metastasis at an early stage. This study aimed to identify ctDNA methylation markers for predicting the recurrence and prognosis of colorectal cancer (CRC) patients, while exploring the impact of the tumor immune microenvironment on patient outcomes. We analyzed 603 overlapping methylation markers in both plasma and tissue samples, developing a risk model to predict CRC recurrence and prognosis.ZNF671 and ZNF132 were identified as key markers in the model, effectively predicting relapse risk in stage III CRC patients (AUC: 0.90) and prognosis in stage IV patients. High-risk patients had a significantly higher early relapse rate (75.4% vs. 20%) compared to the low-risk group, which was more likely to have a High-IS (Immunoscore) classification, associated with a better prognosis. These findings suggest that ZNF671 and ZNF132 methylation levels negatively correlate with Immunoscore and may serve as valuable biomarkers for immunotherapy in CRC, offering potential for better treatment strategies.

Keywords: ctDNA methylation, CRC, Prognosis prediction, Tumor immune microenvironment, ZNF671, ZNF132

Received: 07 Apr 2025; Accepted: 09 Jul 2025.

Copyright: © 2025 Li, Zhou, Ye, Lai, Cui, HE, Yu, Wu, Yan, Lei and Wei. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Wang Wei, General Hospital of Southern Theater Command of the Chinese People's Liberation Army, Guangzhou, China

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material