{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:48:56Z","timestamp":1783039736313,"version":"3.54.6"},"reference-count":44,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,9,16]],"date-time":"2024-09-16T00:00:00Z","timestamp":1726444800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1053206"],"award-info":[{"award-number":["APP1053206"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To explore the associations between cuprotosis\u2010related genes (CRGs) across different stages of liver disease in metabolic dysfunction\u2010associated fatty liver disease (MAFLD), including hepatocellular carcinoma (HCC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      We analysed several bulk RNA sequencing datasets from patients with MAFLD (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009331) and MAFLD\u2010related HCC (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009271) and two MAFLD single\u2010cell RNA sequencing datasets. To investigate the associations between CRGs and MAFLD, we performed differential correlation, logistic regression and functional enrichment analyses. We also validated the findings in an independent Wenzhou PERSONS cohort of MAFLD patients (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009656) used for a genome\u2010wide association study (GWAS).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>GLS<\/jats:italic>\n                      ,\n                      <jats:italic>GCSH<\/jats:italic>\n                      and\n                      <jats:italic>ATP7B<\/jats:italic>\n                      genes showed significant differences across the MAFLD spectrum and were significantly associated with liver fibrosis stages.\n                      <jats:italic>GLS<\/jats:italic>\n                      was closely associated with fibrosis stages in patients with MAFLD and those with MAFLD\u2010related HCC.\n                      <jats:italic>GLS<\/jats:italic>\n                      is predominantly expressed in monocytes and T cells in MAFLD. During the progression of metabolic dysfunction\u2010associated fatty liver to metabolic\u2010associated steatohepatitis,\n                      <jats:italic>GLS<\/jats:italic>\n                      expression in T cells decreased. GWAS revealed that multiple single nucleotide polymorphisms in\n                      <jats:italic>GLS<\/jats:italic>\n                      were associated with clinical indicators of MAFLD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      <jats:italic>GLS<\/jats:italic>\n                      may contribute to liver inflammation and fibrosis in MAFLD mainly through cuprotosis and T\u2010cell activation, promoting the progression of MAFLD to HCC. These findings suggest that cuprotosis may play a role in MAFLD progression, potentially providing new insights into MAFLD pathogenesis.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.15946","type":"journal-article","created":{"date-parts":[[2024,9,17]],"date-time":"2024-09-17T14:14:35Z","timestamp":1726582475000},"page":"5757-5775","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Associations between cuprotosis\u2010related genes and the spectrum of metabolic dysfunction\u2010associated fatty liver disease: An exploratory study"],"prefix":"10.1111","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-8648-7625","authenticated-orcid":false,"given":"Hai\u2010Yang","family":"Yuan","sequence":"first","affiliation":[{"name":"MAFLD Research Center, Department of Hepatology the First Affiliated Hospital of Wenzhou Medical University  Wenzhou 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D.","family":"Byrne","sequence":"additional","affiliation":[{"name":"Southampton National Institute for Health and Care Research Biomedical Research Centre, University Hospital Southampton and University of Southampton Southampton General Hospital  Southampton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4325-3900","authenticated-orcid":false,"given":"Giovanni","family":"Targher","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Research Unit IRCCS Sacro Cuore\u2010Don Calabria Hospital  Negrar di Valpolicella Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Tian","sequence":"additional","affiliation":[{"name":"MAFLD Research Center, Department of Hepatology the First Affiliated Hospital of Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Infectious Jining No.1 People's Hospital  Jining China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin\u2010Lei","family":"Zhang","sequence":"additional","affiliation":[{"name":"MAFLD Research Center, Department of Hepatology the First Affiliated Hospital of Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"George","sequence":"additional","affiliation":[{"name":"Storr Liver Centre Westmead Hospital and University of Sydney  Westmead Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering, School of Ophthalmology and Optometry and Eye Hospital Wenzhou Medical University  Wenzhou 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