Clonorchis sinensis infection alters the methylation and hydroxymethylation of hepatocellular carcinoma

作者：Caibiao Wei, Y L Li, L T Zhou, Yulong Xu, Junxian Chen, Min Fang, Taijun Huang, Jie Gao, Fengfei Liu, Jingyu Su, J ZHU, Weilong Yang · 发表于：Frontiers in Cellular and Infection Microbiology · 年份：2026 · DOI：10.3389/fcimb.2026.1799003 · 研究领域：Parasites and Host Interactions、Epigenetics and DNA Methylation、Ferroptosis and cancer prognosis

Background The molecular mechanisms contributing to the poor prognosis of Clonorchis sinensis ( Cs )-infected hepatocellular carcinoma (HCC) remain poorly understood, especially when it comes to DNA methylation. Methods Using parallel whole-genome bisulfite sequencing (WGBS) and whole-genome oxidative bisulfite sequencing (oxWGBS), we characterized the profiles of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) in Cs -infected HCC tumors and adjacent non-tumor tissues at single-nucleotide resolution. These profiles were compared with data from non- Cs -infected HCC available in the GEO database. Additionally, we investigated the impact of DNA methylation modifications on differential gene expression and prognosis in Cs -infected HCC by analyzing HCC related data from the TCGA database and RNA-seq data from previous studies. Results Here, we reported the methylation and hydroxymethylation landscapes of Cs -infected and Cs -non-infected HCC patients at single-nucleotide resolution by WGBS and oxWGBS, respectively. 29 differentially methylated regions (DMRs) and 13 differentially hydroxymethylated regions (DhMRs) were found in Cs -infected HCC tumor tissues compared to Cs -non-infected HCC tumor tissues. Following, we identified 28 differentially methylated/hydroxymethylated-associated genes (DAGs/DhAGs), two genes (DHDH and KCNQ3) of which were significantly correlated with the overall survival of HCC. Finally, we also revealed that four Cytosine-phosphate-Guanine sit...