{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T05:16:06Z","timestamp":1783055766169,"version":"3.54.6"},"reference-count":63,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      The molecular mechanisms contributing to the poor prognosis of\n                      <jats:italic>Clonorchis sinensis<\/jats:italic>\n                      (\n                      <jats:italic>Cs<\/jats:italic>\n                      )-infected hepatocellular carcinoma (HCC) remain poorly understood, especially when it comes to DNA methylation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      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\n                      <jats:italic>Cs<\/jats:italic>\n                      -infected HCC tumors and adjacent non-tumor tissues at single-nucleotide resolution. These profiles were compared with data from non-\n                      <jats:italic>Cs<\/jats:italic>\n                      -infected HCC available in the GEO database. Additionally, we investigated the impact of DNA methylation modifications on differential gene expression and prognosis in\n                      <jats:italic>Cs<\/jats:italic>\n                      -infected HCC by analyzing HCC related data from the TCGA database and RNA-seq data from previous studies.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Here, we reported the methylation and hydroxymethylation landscapes of\n                      <jats:italic>Cs<\/jats:italic>\n                      -infected and\n                      <jats:italic>Cs<\/jats:italic>\n                      -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\n                      <jats:italic>Cs<\/jats:italic>\n                      -infected HCC tumor tissues compared to\n                      <jats:italic>Cs<\/jats:italic>\n                      -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 sites in the promoter of DAGs\/DhAGs certainly affect the survival outcomes of HCC.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This study provides the first comprehensive characterization of DNA methylome and hydroxymethylome landscapes in\n                      <jats:italic>Cs<\/jats:italic>\n                      -infected HCC, shedding light on the impact of on HCC methylation and offering new insights into the role of\n                      <jats:italic>Cs<\/jats:italic>\n                      in HCC progression. Our findings also highlight the key DMRs\/DhMRs and DAGs\/DhAGs in\n                      <jats:italic>Cs<\/jats:italic>\n                      -infected HCC tumors, which could serve as promising epigenetic biomarkers for predicting the prognosis and therapeutic targets of\n                      <jats:italic>Cs<\/jats:italic>\n                      -associated HCC.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1799003","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T04:22:34Z","timestamp":1783052554000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Clonorchis sinensis infection alters the methylation and hydroxymethylation of hepatocellular carcinoma"],"prefix":"10.3389","volume":"16","author":[{"given":"Caibiao","family":"Wei","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory, Guangxi Medical University Cancer Hospital","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanbo","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Blood Transfusion, Guangxi Medical University Cancer Hospital","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingling","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Guangxi Medical University Cancer Hospital","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulong","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The First Affiliated Hospital of Guangxi Medical University","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junxian","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Guangxi Medical University Cancer Hospital","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Guangxi Medical University Cancer Hospital","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taijun","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Guangxi Medical University Cancer Hospital","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Guangxi Medical University Cancer Hospital","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengfei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Guangxi Medical University Cancer Hospital","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyu","family":"Su","sequence":"additional","affiliation":[{"name":"Genetic Metabolism Center Laboratory, Guangxi Zhuang Autonomous Region Maternal and Child Health Care Hospital","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Kang","family":"Zhu","sequence":"additional","affiliation":[{"name":"Institute of Advanced Biotechnology, Institute of Homeostatic Medicine, and School of Medicine, Southern University of Science and Technology","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weilong","family":"Yang","sequence":"additional","affiliation":[{"name":"Guangzhou Women and Children's Medical Center, Guangzhou Medical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1186\/s12864-021-08123-x","article-title":"Comparative methylation and RNA-seq expression analysis in CpG context to identify genes involved in backfat vs. liver diversification in Nanchukmacdon pig","volume":"22","author":"Arora","year":"2021","journal-title":"BMC Genomics"},{"key":"B2","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1007\/s12672-024-01115-9","article-title":"Understanding the heterogeneity in liver hepatocellular carcinoma with a special focus on Malignant cell through single-cell analysis","volume":"15","author":"Bao","year":"2024","journal-title":"Discov. 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