{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T21:59:15Z","timestamp":1785535155062,"version":"3.56.0"},"reference-count":27,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T00:00:00Z","timestamp":1740096000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T00:00:00Z","timestamp":1740096000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100004917","name":"Cancer Prevention and Research Institute of Texas","doi-asserted-by":"publisher","award":["RP200509"],"award-info":[{"award-number":["RP200509"]}],"id":[{"id":"10.13039\/100004917","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004917","name":"Cancer Prevention and Research Institute of Texas","doi-asserted-by":"publisher","award":["RP200081"],"award-info":[{"award-number":["RP200081"]}],"id":[{"id":"10.13039\/100004917","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004917","name":"Cancer Prevention and Research Institute of Texas","doi-asserted-by":"publisher","award":["RP230063"],"award-info":[{"award-number":["RP230063"]}],"id":[{"id":"10.13039\/100004917","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2025,3]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background and Aim<\/jats:title>\n Metabolic dysfunction\u2010associated steatotic liver diseases (MASLD), also known as non\u2010alcoholic fatty liver diseases (NAFLD), have become a leading risk factor for hepatocellular carcinoma (HCC) in Western countries. NAFLD progresses from simple steatosis to HCC, with advanced liver fibrosis (ALF) and metabolic dysfunction\u2010associated steatohepatitis (MASH) or non\u2010alcoholic steatohepatitis (NASH) representing the two preceding high\u2010risk stages.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n We analysed changes in the DNA methylation landscape from simple steatosis to ALF or NASH and determined their relevance in gene regulation and HCC survival. Methylomic datasets generated from applying the Illumina 450K BeadChip on human MASLD\/NAFLD liver samples were analysed using integrative data analyses to identify differentially methylated regions (DMRs) associated with ALF (F3\/4 vs. F0\/1) or non\u2010fibrotic NASH (NASH\u2010F0\/1 vs. NAFLD\u2010F0\/1).<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Gene Set Enrichment Analysis (GSEA) of genes associated with fibrosis\u2010DMRs showed enrichment in xenobiotic metabolism, UV response and hypoxia pathways. Expression of 25 DMR\u2010associated genes showed significant associations with HCC survival outcomes, including 16 genes with fibrosis\u2010DMRs and 2 with NASH\u2010DMRs mapped to their promoter regions. Binding motifs of seven transcription factors (TFs) were enriched in fibrosis\u2010DMRs. Four DMR\u2010associated genes (ESR1, TYW3, CLGN and TUBB) displayed an inverse relationship between promoter methylation and gene expression during human MASLD progression, which was further validated in a mouse MASLD model.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n We propose a model in which changes in promoter DNA methylation during NAFLD progression regulate gene expression, impacting HCC survival outcomes.<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/liv.70040","type":"journal-article","created":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T08:41:16Z","timestamp":1740127276000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["DNA<\/scp>\n Methylation and Target Gene Expression in Fatty Liver Progression From Simple Steatosis to Advanced Fibrosis"],"prefix":"10.1111","volume":"45","author":[{"given":"Jin","family":"Li","sequence":"first","affiliation":[{"name":"Institute of Biosciences and Technology Texas A&M University Health Science Center Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqin","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Biosciences and Technology Texas A&M University Health Science Center Houston Texas USA"},{"name":"Department of Translational Medical Sciences, School of Medicine Texas A&M University Health Science Center Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tran T.","family":"Tran","sequence":"additional","affiliation":[{"name":"Institute of Biosciences and Technology Texas A&M University Health Science Center Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miryoung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, School of Public Health The University of Texas Health Science Center at Houston Brownsville Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8357-0812","authenticated-orcid":false,"given":"Robert Y. L.","family":"Tsai","sequence":"additional","affiliation":[{"name":"Institute of Biosciences and Technology Texas A&M University Health Science Center Houston Texas USA"},{"name":"Department of Translational Medical Sciences, School of Medicine Texas A&M University Health Science Center Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,2,21]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.29210"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.3322\/canjclin.55.2.74"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1001683"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.29936"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdw027"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.17158"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.11.034"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCG.0000000000000925"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2014.04.014"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22083820"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12915-023-01533-1"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2013.07.047"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2013.07.004"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1412759111"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13148-018-0525-9"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-31886-5"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/hepr.12992"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgx005"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1080\/15592294.2017.1294305"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13148-021-01129-y"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt684"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26661"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.2217\/epi-2016-0087"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1210\/js.2018-00122"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2018.03.011"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/biostatistics\/kxj037"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyr238"}],"container-title":["Liver International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.70040","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/liv.70040","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.70040","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T19:25:01Z","timestamp":1772997901000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/liv.70040"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,21]]},"references-count":27,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,3]]}},"alternative-id":["10.1111\/liv.70040"],"URL":"https:\/\/doi.org\/10.1111\/liv.70040","archive":["Portico"],"relation":{},"ISSN":["1478-3223","1478-3231"],"issn-type":[{"value":"1478-3223","type":"print"},{"value":"1478-3231","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,21]]},"assertion":[{"value":"2024-12-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70040"}}