5-hydroxymethylcytosines from circulating cell-free DNA as noninvasive prognostic markers for gastric cancer

Yingli Fu, Donghui Cao, Yanhua Wu, Zhifang Jia, Yangyu Zhang, Chenhao Fu, Xueyuan Cao and Jing Jiang

PLOS ONE, 2025, vol. 20, issue 11, 1-13

Abstract: Background: Prognostic assessment plays a crucial role in guiding clinical management and treatment decisions for gastric cancer patients. The enrichment characteristics of 5-hydroxymethylcytosine (5hmC) in circulating cell-free DNA (cfDNA) has emerged as potential prognostic epigenetic markers. Methods: Using 5hmC-Seal combined with next-generation sequencing (NGS), we profiled the genome-wide distribution of 5hmC in plasma cfDNA samples from 51 gastric cancer patients. Prognostic biomarkers were selected via random survival forest and Cox proportion hazards models, and a prognostic model was subsequently constructed. Results: Seven prognostic biomarker genes were identified, and the 7-gene prognostic model demonstrated a concordance index (C-index) of 0.892 (95% CI = 0.786–0.998). Patients in the high risk group had a significantly worse overall survival (OS) than those in low-risk group (log-rank P = 0.00012). When the cfDNA 5hmC risk-score was integrated with the traditional clinical characteristics, the C-index increased from 0.819 (95% CI = 0.727–0.911) to 0.904 (95% CI = 0.853–0.955). Multivariate analysis adjusted for age, TNM stage, and chemotherapy confirmed that a high risk-score of cfDNA 5hmC model was an independent predictor of poor OS (hazard ratio [HR]=27.47, 95% CI = 3.28–230.25). Conclusion: cfDNA 5hmC serves as an effective prognostic biomarker with high predictive value for the long-term survival in postoperative gastric cancer patients.

Date: 2025
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0335654

DOI: 10.1371/journal.pone.0335654

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