{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T23:46:06Z","timestamp":1772063166656,"version":"3.50.1"},"reference-count":42,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2008,6,6]],"date-time":"2008-06-06T00:00:00Z","timestamp":1212710400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2008,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Despite the progress of therapy, outcomes of advanced hepatoblastoma patients who are refractory to standard preoperative chemotherapy remain unsatisfactory. To improve the mortality rate, novel prognostic markers are needed for better therapy planning. We examined the methylation status of 13 candidate tumor suppressor genes in 20 hepatoblastoma tumors by conventional methylation\u2010specific PCR (MSP) and found hypermethylation in 3 of the 13 genes. We analyzed the methylation status of these 3 genes (<jats:italic>RASSF1A<\/jats:italic>, <jats:italic>SOCS1<\/jats:italic> and <jats:italic>CASP8<\/jats:italic>) in 97 tumors and found hypermethylation in 30.9, 33.0 and 15.5%, respectively. Univariate analysis showed that only the methylation status of <jats:italic>RASSF1A<\/jats:italic> but not the other 2 genes predicted the outcome, and multivariate analysis showed a weak contribution of <jats:italic>RASSF1A<\/jats:italic> methylation to overall survival. Using quantitative MSP, we found <jats:italic>RASSF1A<\/jats:italic> methylation in 44.3% of the 97 tumors. <jats:italic>CTNNB1<\/jats:italic> mutation was detected in 67.0% of the 97 tumors. While univariate analysis demonstrated <jats:italic>RASSF1A<\/jats:italic> methylation, <jats:italic>CTNNB1<\/jats:italic> mutation and other clinicopathological variables as prognostic factors, multivariate analysis identified <jats:italic>RASSF1A<\/jats:italic> methylation (<jats:italic>p<\/jats:italic> = 0.043; relative risk 9.39) and the disease stage (<jats:italic>p<\/jats:italic> = 0.002; relative risk 7.67) but not <jats:italic>CTNNB1<\/jats:italic> mutation as independent prognostic factors. In survival analysis of 33 patients in stage 3B or 4, patients with unmethylated tumor had better overall survival than those with methylated tumor (<jats:italic>p<\/jats:italic> = 0.035). <jats:italic>RASSF1A<\/jats:italic> methylation may be a promising molecular\u2010genetic marker to predict the treatment outcome and may be used to stratify patients when clinical trials are carried out. \u00a9 2008 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.23613","type":"journal-article","created":{"date-parts":[[2008,6,6]],"date-time":"2008-06-06T20:48:01Z","timestamp":1212785281000},"page":"1117-1125","source":"Crossref","is-referenced-by-count":49,"title":["The methylation status of <i>RASSF1A<\/i> promoter predicts responsiveness to chemotherapy and eventual cure in hepatoblastoma 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