{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T21:39:12Z","timestamp":1788471552947,"version":"build-2803163510"},"reference-count":48,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":126,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2015,8]]},"abstract":"<jats:p>In addition to DNA methylation, hydroxymethylation of DNA is recognized as a novel epigenetic mark. Primary liver cancers, i.e., hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC), are highly prevalent but epigenetically poorly characterized, so far. In the present study we measured global methylcytosine (mCyt) and hydroxymethylcytosine (hmCyt) in HCC and CC tissues and in peripheral blood mononuclear cell (PBMC) DNA to define mCyt and hmCyt status and, accordingly, the survival rate. Both mCyt and hmCyt were measured by a liquid chromatography\/tandem mass spectrometry method in neoplastic and homologous nonneoplastic tissues, i.e., liver and gallbladder, and in PBMCs of 31 HCC and 16 CC patients. Content of mCyt was notably lower in HCC than in CC tissues (3.97% versus 5.26%, respectively; <jats:italic toggle=\"yes\">P<\/jats:italic>\u2009&lt;\u20090.0001). Significantly reduced mCyt was also detected in HCC compared to nonneoplastic tissue (3.97% versus 4.82% mCyt, respectively; <jats:italic toggle=\"yes\">P<\/jats:italic>\u2009&lt;\u20090.0001), but no such difference was found for CC versus homologous nonneoplastic tissue. Hydroxymethylation was significantly decreased in HCC versus nonneoplastic liver tissue (0.044 versus 0.128, respectively; <jats:italic toggle=\"yes\">P<\/jats:italic>\u2009&lt;\u20090.0001) and in CC versus both liver and gallbladder nonneoplastic tissue (0.030 versus 0.124, <jats:italic toggle=\"yes\">P<\/jats:italic>\u2009=\u20090.026, and 0.030 versus 0.123, <jats:italic toggle=\"yes\">P<\/jats:italic>\u2009=\u20090.006, respectively). When the survival rate was evaluated according to mCyt PBMC content by Kaplan\u2010Meier analysis, patients with mCyt \u22655.59% had a significantly higher life expectancy than those with mCyt &lt;5.59% (<jats:italic toggle=\"yes\">P<\/jats:italic>\u2009=\u20090.034) at a follow\u2010up period up to 48 months. <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>: A significant DNA hypomethylation distinguishes HCC from CC, while DNA hypo\u2010hydroxymethylation characterizes both HCC and CC, and a PBMC DNA mCyt content \u22655.59% relates to a favorable outcome in primary liver cancers. (H<jats:sc>epatology<\/jats:sc> 2015;62:496\u2013504<\/jats:p>","DOI":"10.1002\/hep.27823","type":"journal-article","created":{"date-parts":[[2015,4,2]],"date-time":"2015-04-02T21:37:50Z","timestamp":1428010670000},"page":"496-504","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":59,"title":["Global DNA methylation and hydroxymethylation differ in hepatocellular carcinoma and cholangiocarcinoma and relate to survival rate"],"prefix":"10.1097","volume":"62","author":[{"given":"Silvia","family":"Udali","sequence":"first","affiliation":[{"name":"Department of Medicine and the University Laboratory for Medical Research, University of Verona School of Medicine,Verona,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Guarini","sequence":"additional","affiliation":[{"name":"Department of Medicine and the University Laboratory for Medical Research, University of Verona School of Medicine,Verona,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Moruzzi","sequence":"additional","affiliation":[{"name":"Department of Medicine and the University Laboratory for Medical Research, University of Verona School of Medicine,Verona,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Ruzzenente","sequence":"additional","affiliation":[{"name":"Department of Surgery,University of Verona School of Medicine,Verona,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie A.","family":"Tammen","sequence":"additional","affiliation":[{"name":"Tufts University School of Nutrition Science and Policy,Boston,MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Guglielmi","sequence":"additional","affiliation":[{"name":"Department of Surgery,University of Verona School of Medicine,Verona,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Conci","sequence":"additional","affiliation":[{"name":"Department of Surgery,University of Verona School of Medicine,Verona,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Pattini","sequence":"additional","affiliation":[{"name":"Department of Medicine and the University Laboratory for Medical Research, University of Verona School of Medicine,Verona,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliviero","family":"Olivieri","sequence":"additional","affiliation":[{"name":"Department of Medicine and the University Laboratory for Medical Research, University of Verona School of Medicine,Verona,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Corrocher","sequence":"additional","affiliation":[{"name":"Department of Medicine and the University Laboratory for Medical Research, University of Verona School of Medicine,Verona,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang\u2010Woon","family":"Choi","sequence":"additional","affiliation":[{"name":"Tufts University School of Nutrition Science and Policy,Boston,MA"},{"name":"Chaum Life Center, CHA University,Seoul,Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simonetta","family":"Friso","sequence":"additional","affiliation":[{"name":"Department of Medicine and the University Laboratory for Medical Research, University of Verona School of Medicine,Verona,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2015,4,28]]},"reference":[{"key":"hep27823-bib-0001-20241017","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1038\/nature12750","article-title":"TET enzymes, TDG and the dynamics of DNA 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