{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T13:33:04Z","timestamp":1751463184448},"reference-count":26,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,1,22]],"date-time":"2020-01-22T00:00:00Z","timestamp":1579651200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007591","name":"Akiyama Life Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007591","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["KAKENHI Grant Numbers JP15K10915","KAKENHI Grant Numbers JP16K15740"],"award-info":[{"award-number":["KAKENHI Grant Numbers JP15K10915","KAKENHI Grant Numbers JP16K15740"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008732","name":"Uehara Memorial Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008732","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Hepatology Research"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:sec><jats:title>Aim<\/jats:title><jats:p>Most hepatoblastoma patients undergo pre\/postoperative cisplatin treatment. Approximately 20% patients are cisplatin resistant, and show poor prognosis and high recurrence rates. However, some cisplatin\u2010sensitive patients show early recurrence. We consider that a small population of cisplatin\u2010resistant cells may remain after preoperative chemotherapy. Previous studies showed a correlation between DNA hypermethylation and hepatoblastoma progression. Here, we examined whether DNA hypermethylation was related to cisplatin resistance and could be a potential indicator for cisplatin as postoperative chemotherapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We extracted DNA from 43 resected hepatoblastoma tumors. Methylation array analyses were performed in 11 samples, including six cisplatin\u2010sensitive and five cisplatin\u2010resistant samples. We also performed cDNA microarray analysis in parental and cisplatin\u2010resistant HuH6 cells. Through comparison of the datasets, we selected the strongest correlated cisplatin\u2010resistant candidate gene. Using bisulfite pyrosequencing, the candidate gene methylation level was assessed in 38 cisplatin\u2010sensitive patients after checking its usefulness as a substitute modality of methylation array. Correlations between the methylation status and clinical data were analyzed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>CSF3R<\/jats:italic> was the strongest correlated variable. Bisulfite pyrosequencing analysis also confirmed <jats:italic>CSF3R<\/jats:italic> was significantly hypermethylated in cisplatin\u2010resistant patients. Among the 38 cisplatin\u2010sensitive patients, recurrence curves showed that the <jats:italic>CSF3R<\/jats:italic> high methylation patients had significantly higher recurrence than <jats:italic>CSF3R<\/jats:italic> low methylation patients. The recurrence curve of methylation high patients was similar to that of cisplatin\u2010resistant patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings suggested that <jats:italic>CSF3R<\/jats:italic> hypermethylation was related to cisplatin resistance in HB patients and could be a predictor of postoperative chemotherapy, and indicate that <jats:italic>CSF3R<\/jats:italic> high methylation patients should be treated with non\u2010CDDP regimens.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hepr.13479","type":"journal-article","created":{"date-parts":[[2020,1,2]],"date-time":"2020-01-02T03:33:57Z","timestamp":1577936037000},"page":"598-606","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Hypermethylation of <i>CSF3R<\/i> is a novel cisplatin resistance marker and predictor of response to postoperative chemotherapy in hepatoblastoma"],"prefix":"10.1111","volume":"50","author":[{"given":"Sunao","family":"Fujiyoshi","sequence":"first","affiliation":[{"name":"Department of Gastroenterological Surgery 1 Hokkaido University Graduate School of Medicine  Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shohei","family":"Honda","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery 1 Hokkaido University Graduate School of Medicine  Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masashi","family":"Minato","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery 1 Hokkaido University Graduate School of Medicine  Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Momoko","family":"Ara","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery 1 Hokkaido University Graduate School of Medicine  Sapporo 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