{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T23:00:31Z","timestamp":1789426831454,"version":"build-2803163510"},"reference-count":36,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2012,1,13]],"date-time":"2012-01-13T00:00:00Z","timestamp":1326412800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2012,3]]},"abstract":"<jats:p>Malignant pleural mesothelioma (MPM) usually develops pleural fluid. We investigated the value of DNA methylation in the pleural fluid for differentiating MPM from lung cancer (LC). Pleural fluid was collected from 39 patients with MPM, 46 with LC, 25 with benign asbestos pleurisy (BAP) and 30 with other causes. The methylation of <jats:italic>O<\/jats:italic><jats:sup><jats:italic>6<\/jats:italic><\/jats:sup><jats:italic>\u2010methylguanine\u2010DNA methyltransferase<\/jats:italic> (<jats:italic>MGMT<\/jats:italic>), <jats:italic>p16<\/jats:italic><jats:sup><jats:italic>INK4a<\/jats:italic><\/jats:sup>, <jats:italic>ras association domain family 1A<\/jats:italic> (<jats:italic>RASSF1A<\/jats:italic>), <jats:italic>death\u2010associated protein kinase<\/jats:italic> (<jats:italic>DAPK<\/jats:italic>), and <jats:italic>retinoic acid receptor \u03b2<\/jats:italic> (<jats:italic>RAR\u03b2<\/jats:italic>) was examined using quantitative real\u2010time PCR. DNA methylation of <jats:italic>RASSF1A<\/jats:italic>, <jats:italic>p16<\/jats:italic><jats:sup><jats:italic>INK4a<\/jats:italic><\/jats:sup>, <jats:italic>RAR\u03b2<\/jats:italic>, <jats:italic>MGMT<\/jats:italic> and <jats:italic>DAPK<\/jats:italic> was detected in 12 (30.8%), 3 (7.7%), 11 (28.2%), 0 (0.0%) and five patients (12.8%) with MPM, and in 22 (47.8%), 14 (30.4%), 24 (52.2%), 1 (2.2%) and six patients (13.0%) with LC, respectively. The mean methylation ratios of <jats:italic>RASSF1A<\/jats:italic>, <jats:italic>p16<\/jats:italic><jats:sup><jats:italic>INK4a<\/jats:italic><\/jats:sup> and <jats:italic>RAR\u03b2<\/jats:italic> were 0.37 (range 0.0\u20132.84), 0.11 (0.0\u20132.67) and 0.44 (0.0\u20133.32) in MPM, and 0.87 (0.0\u20133.14), 1.16 (0.0\u20135.35) and 1.69 (0.0\u20136.49) in LC, respectively. The methylation ratios for the three genes were significantly higher in LC than in MPM (<jats:italic>RASSF1A<\/jats:italic>, <jats:italic>P<\/jats:italic>\u2003=\u20030.039; <jats:italic>p16<\/jats:italic><jats:sup><jats:italic>INK4a<\/jats:italic><\/jats:sup>, <jats:italic>P\u2003<\/jats:italic>=\u20030.005; and <jats:italic>RAR\u03b2<\/jats:italic>, <jats:italic>P<\/jats:italic>\u2003=\u20030.002). Patients with methylation in at least one gene were 3.51 (95% confidence interval, 1.09\u201311.34) times more likely to have LC. Hypermethylation seemed no greater with MPM than with BAP. Extended exposure to asbestos (\u226730\u2003years) was correlated with an increased methylation frequency (<jats:italic>P\u2003=\u2003<\/jats:italic>0.020). Hypermethylation of tumor suppressor genes in pleural fluid DNA has the potential to be a valuable marker for differentiating MPM from LC. (<jats:italic>Cancer Sci<\/jats:italic> 2012; 103: 510\u2013514)<\/jats:p>","DOI":"10.1111\/j.1349-7006.2011.02180.x","type":"journal-article","created":{"date-parts":[[2011,12,7]],"date-time":"2011-12-07T11:03:05Z","timestamp":1323255785000},"page":"510-514","source":"Crossref","is-referenced-by-count":34,"title":["Aberrant DNA methylation profile in pleural fluid for differential diagnosis of malignant pleural mesothelioma"],"prefix":"10.1111","volume":"103","author":[{"given":"Masanori","family":"Fujii","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobukazu","family":"Fujimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akio","family":"Hiraki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichi","family":"Gemba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keisuke","family":"Aoe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeki","family":"Umemura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Katayama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nagio","family":"Takigawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuyuki","family":"Kiura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsune","family":"Tanimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takumi","family":"Kishimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,1,13]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-010-0834-7"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19930715)72:2<389::AID-CNCR2820720213>3.0.CO;2-V"},{"key":"e_1_2_7_4_2","first-page":"94","volume-title":"Pleural Diseases","author":"Light R","year":"1995"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1843.2008.01291.x"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2007.077958"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1378\/chest.126.4.1195"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1827.2007.02080.x"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200511-1789OC"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.3892\/etm_00000048"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc053112"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12199-007-0014-9"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.7.687"},{"key":"e_1_2_7_14_2","first-page":"61","article-title":"DNA methylation profiles of lung tumors","volume":"1","author":"Toyooka S","year":"2001","journal-title":"Mol Cancer Ther"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-04-2363"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgn169"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/23.7.1127"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2007.06.015"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2004.08.003"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgn059"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.22576"},{"key":"e_1_2_7_22_2","unstructured":"World Health OrganizationHistological typing of lungs and pleural tumors 3rd edn. 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