{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T11:31:41Z","timestamp":1792150301122,"version":"4.4.0"},"reference-count":70,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Functional DNA methylation abnormalities are a hallmark of human cancers and may be a promising biomarker for their early diagnosis. Moreover, the largest methylation differences can improve the sensitivity of noninvasive diagnoses of solid tumors. We combined whole\u2010genome bisulfite sequencing (WGBS) and mRNA\u2010seq data from 33 paired hepatocellular carcinoma (HCC) and adjacent tissues to identify methylation markers that could be used for noninvasive diagnosis in blood samples. Methylation markers were selected according to the following criteria: differentially methylated regions (DMR) located in the promoter region with large differences in methylation (\u0394\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2009&gt;\u20090.3) and inverse correlation with matched gene expression (cor &lt;\u2009\u22120.3). Cell\u2010free DNA (cfDNA) from 48 patients with HCC and 24 normal participants was used to verify the performance of me\n                    <jats:italic>TSPYL5<\/jats:italic>\n                    using qMSP. Integrated WGBS and transcriptomic data analysis identified eight target promoter hyper\u2010DMRs. After confirming the WGBS profiles of genes in peripheral blood mononuclear cells, me\n                    <jats:italic>TSPYL5<\/jats:italic>\n                    was selected to further verify the plasma cfDNA samples by qMSP. The results of plasma validation showed that the methylation detection of me\n                    <jats:italic>TSPYL5<\/jats:italic>\n                    was sensitive for identifying HCC, with a sensitivity and specificity of 85.4% and 100%, respectively. Pan\u2010cancer analysis found that the methylation level of\n                    <jats:italic>TSPYL5<\/jats:italic>\n                    was elevated in multiple cancer types, indicating that it lacks cancer\u2010type specificity; however, this result does not affect its application value in monitoring high\u2010risk populations of HCC. By analyzing and integrating all available high\u2010throughput epigenomic and transcriptomic data from human HCC tissues, we identified eight regions as potential diagnostic biomarkers for HCC. Integrative analyses of epigenomic and transcriptomic data provide an efficient method to identify diagnostic biomarkers for human cancers. Methylated\n                    <jats:italic>TSPYL5<\/jats:italic>\n                    in plasma is a promising biomarker for the detection and screening of HCC.\n                  <\/jats:p>","DOI":"10.1002\/mc.70101","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T16:59:32Z","timestamp":1772989172000},"page":"603-614","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Whole\u2010Genome Bisulfite Sequencing Identifies Blood\u2010Based DNA Methylation Biomarker for Hepatocellular Carcinoma"],"prefix":"10.1002","volume":"65","author":[{"given":"Junsheng","family":"Zhao","sequence":"first","affiliation":[{"name":"State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital Zhejiang University School of Medicine Hangzhou China"},{"name":"Bioinformatic Center, Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Shulan (Hangzhou) Hospital Affiliated to Shulan International Medical College Zhejiang Shuren University Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sijia","family":"Shen","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital Zhejiang University School of Medicine Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Bioinformatic Center, Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Shulan (Hangzhou) Hospital Affiliated to Shulan International Medical College Zhejiang Shuren University Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases ShuLan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University, Shulan International Medical College Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, Renji Hospital, School of Medicine Shanghai Jiao Tong University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4590-9181","authenticated-orcid":false,"given":"Hainv","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Shulan (Hangzhou) Hospital Affiliated to Shulan International Medical College Zhejiang Shuren University Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6945-0593","authenticated-orcid":false,"given":"Lanjuan","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital Zhejiang University School of Medicine Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,1]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31288"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jncc.2020.12.001"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.3350\/cmh.2019.0012"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/brv.12457"},{"issue":"1","key":"e_1_2_13_6_1","first-page":"79","article-title":"Hepatitis C Virus and Hepatocellular Carcinoma: A Narrative Review","volume":"6","author":"Axley P.","year":"2018","journal-title":"Journal of Clinical and Translational 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