{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T12:12:40Z","timestamp":1768738360644,"version":"3.49.0"},"reference-count":32,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2016,4,27]],"date-time":"2016-04-27T00:00:00Z","timestamp":1461715200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003478","name":"Ministry of Health, Labour and Welfare","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003478","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science, and Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2016,6]]},"abstract":"<jats:p>Hepatoblastoma (<jats:styled-content style=\"fixed-case\">HB<\/jats:styled-content>) is very rare but the most common malignant neoplasm of the liver occurring in children. Despite improvements in therapy, outcomes for patients with advanced <jats:styled-content style=\"fixed-case\">HB<\/jats:styled-content> that is refractory to standard preoperative chemotherapy remain unsatisfactory. To improve the survival rate among this group, identification of novel prognostic markers and therapeutic targets is needed. We have previously reported that altered <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> methylation patterns are of biological and clinical importance in <jats:styled-content style=\"fixed-case\">HB<\/jats:styled-content>. In the present study, using genome\u2010wide methylation analysis and bisulfite pyrosequencing with specimens from <jats:styled-content style=\"fixed-case\">HB<\/jats:styled-content> tumors, we detected nine methylated genes. We then focused on four of those genes, <jats:italic><jats:styled-content style=\"fixed-case\">GPR<\/jats:styled-content>180<\/jats:italic>,<jats:italic> <jats:styled-content style=\"fixed-case\">MST<\/jats:styled-content>1R<\/jats:italic>,<jats:italic> <jats:styled-content style=\"fixed-case\">OCIAD<\/jats:styled-content>2<\/jats:italic>, and <jats:italic><jats:styled-content style=\"fixed-case\">PARP<\/jats:styled-content>6<\/jats:italic>, because they likely encode tumor suppressors and their increase of methylation was associated with a poor prognosis. The methylation status of the four genes was also associated with age at diagnosis, and significant association with the presence of metastatic tumors was seen in three of the four genes. Multivariate analysis revealed that the presence of metastatic tumors and increase of methylation of <jats:italic><jats:styled-content style=\"fixed-case\">GPR<\/jats:styled-content>180<\/jats:italic> were independent prognostic factors affecting event\u2010free survival. These findings indicate that the four novel tumor suppressor candidates are potentially useful molecular markers predictive of a poor outcome in <jats:styled-content style=\"fixed-case\">HB<\/jats:styled-content> patients, which may serve as the basis for improved therapeutic strategies when clinical trials are carried out.<\/jats:p>","DOI":"10.1111\/cas.12928","type":"journal-article","created":{"date-parts":[[2016,3,19]],"date-time":"2016-03-19T02:04:19Z","timestamp":1458353059000},"page":"812-819","source":"Crossref","is-referenced-by-count":34,"title":["Clinical prognostic value of <scp>DNA<\/scp> methylation in hepatoblastoma: Four novel tumor suppressor candidates"],"prefix":"10.1111","volume":"107","author":[{"given":"Shohei","family":"Honda","sequence":"first","affiliation":[{"name":"Department of Gastroenterological Surgery I Hokkaido University Graduate School of Medicine Sapporo 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