{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T13:07:26Z","timestamp":1789650446296,"version":"4.0.0"},"reference-count":52,"publisher":"Ovid Technologies (Wolters Kluwer Health)","license":[{"start":{"date-parts":[[2018,5,1]],"date-time":"2018-05-01T00:00:00Z","timestamp":1525132800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,5,1]],"date-time":"2020-05-01T00:00:00Z","timestamp":1588291200000},"content-version":"vor","delay-in-days":731,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"content-domain":{"domain":["clinicalkey.jp","clinicalkey.com","clinicalkey.es","clinicalkey.fr","clinicalkey.com.au","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["International Journal of Surgery"],"published-print":{"date-parts":[[2018,5]]},"DOI":"10.1016\/j.ijsu.2018.03.053","type":"journal-article","created":{"date-parts":[[2018,3,27]],"date-time":"2018-03-27T12:58:08Z","timestamp":1522155488000},"page":"178-183","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":22,"special_numbering":"C","title":["DNA methylation as an epigenetic regulator of gallbladder cancer: An overview"],"prefix":"10.1097","volume":"53","author":[{"given":"Jibran Sualeh","family":"Muhammad","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Rizwan","family":"Khan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kulsoom","family":"Ghias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"issue":"1","key":"10.1016\/j.ijsu.2018.03.053_bib1","doi-asserted-by":"crossref","first-page":"5","DOI":"10.3322\/caac.21254","article-title":"Cancer statistics, 2015","volume":"65","author":"Siegel","year":"2015","journal-title":"CA A Cancer J. Clin."},{"issue":"2","key":"10.1016\/j.ijsu.2018.03.053_bib2","doi-asserted-by":"crossref","first-page":"172","DOI":"10.5009\/gnl.2012.6.2.172","article-title":"Epidemiology of gallbladder disease: cholelithiasis and cancer","volume":"6","author":"Stinton","year":"2012","journal-title":"Gut Liver"},{"issue":"5","key":"10.1016\/j.ijsu.2018.03.053_bib3","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1002\/jso.24546","article-title":"Global epidemiological trends and variations in the burden of gallbladder cancer","volume":"115","author":"Are","year":"2017","journal-title":"J. Surg. Oncol."},{"key":"10.1016\/j.ijsu.2018.03.053_bib4","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1002\/(SICI)1097-0215(20000201)85:3<325::AID-IJC5>3.0.CO;2-J","article-title":"Cancer incidents in karachi Pakistan: first results from karachi cancer registry","volume":"85","author":"Bhurgri","year":"2000","journal-title":"Int. J. Canc."},{"key":"10.1016\/j.ijsu.2018.03.053_bib5","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1186\/1477-7819-9-164","article-title":"Risk factors of gallbladder cancer in Karachi-a case-control study","volume":"9","author":"Alvi","year":"2011","journal-title":"World J. Surg. Oncol."},{"issue":"6","key":"10.1016\/j.ijsu.2018.03.053_bib6","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.ijsu.2011.07.001","article-title":"Gallbladder intestinal metaplasia in Pakistani patients with gallstones","volume":"9","author":"Khan","year":"2011","journal-title":"Int. J. Surg."},{"issue":"5","key":"10.1016\/j.ijsu.2018.03.053_bib7","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1055\/s-0029-1237423","article-title":"Epigenetics: definition, mechanisms and clinical perspective","volume":"27","author":"Dupont","year":"2009","journal-title":"Semin. Reprod. Med."},{"issue":"2","key":"10.1016\/j.ijsu.2018.03.053_bib8","doi-asserted-by":"crossref","first-page":"523","DOI":"10.3892\/or.2013.2913","article-title":"Epigenetic regulation and cancer (review)","volume":"31","author":"Chen","year":"2014","journal-title":"Oncol. Rep."},{"issue":"S1","key":"10.1016\/j.ijsu.2018.03.053_bib9","doi-asserted-by":"crossref","first-page":"82","DOI":"10.4103\/0971-5916.191792","article-title":"Adenomatous polylosis coli (APC) gallbladder: epigenetic regulation of APC in the molecular pathogenesis of gallbladder cancer","volume":"143","author":"Tekcham","year":"2016","journal-title":"Indian J. Med. Res."},{"key":"10.1016\/j.ijsu.2018.03.053_bib10","doi-asserted-by":"crossref","first-page":"6126","DOI":"10.1158\/1078-0432.CCR-04-0579","article-title":"Aberrant promoter hypermethylation of multiple genes in gallbladder carcinoma and chronic cholecystitis","volume":"10","author":"Takahashi","year":"2004","journal-title":"Clin. Canc. Res."},{"key":"10.1016\/j.ijsu.2018.03.053_bib11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2407-15-1","article-title":"Radioactive (125)I seeds inhibit cell growth and epithelial-mesenchymal transition in human glioblastoma multiforme via a ROS-mediated signaling pathway","volume":"15","author":"Tian","year":"2015","journal-title":"BMC Canc."},{"issue":"11","key":"10.1016\/j.ijsu.2018.03.053_bib12","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1056\/NEJMra072067","article-title":"Epigenetics in cancer","volume":"358","author":"Esteller","year":"2008","journal-title":"N. Engl. J. Med."},{"issue":"5532","key":"10.1016\/j.ijsu.2018.03.053_bib13","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1126\/science.1063852","article-title":"The role of DNA methylation in mammalian epigenetics","volume":"293","author":"Jones","year":"2001","journal-title":"Science"},{"issue":"1","key":"10.1016\/j.ijsu.2018.03.053_bib14","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0016080","article-title":"Hypermethylation of tumor suppressor genes involved in critical regulatory pathways for developing a blood-based test in breast cancer","volume":"6","author":"Radpour","year":"2011","journal-title":"PLoS One"},{"issue":"10","key":"10.1016\/j.ijsu.2018.03.053_bib15","doi-asserted-by":"crossref","first-page":"2272","DOI":"10.1002\/ijc.30657","article-title":"Autophagy impairment by Helicobacter pylori-induced methylation silencing of MAP1LC3Av1 promotes gastric carcinogenesis","volume":"140","author":"Muhammad","year":"2017","journal-title":"Int. J. Canc."},{"key":"10.1016\/j.ijsu.2018.03.053_bib16","doi-asserted-by":"crossref","first-page":"6985","DOI":"10.1007\/s13277-015-3412-4","article-title":"MicroRNA signatures in total peripheral blood of gallbladder cancer patients","volume":"36","author":"Li","year":"2015","journal-title":"Tumor Biol."},{"key":"10.1016\/j.ijsu.2018.03.053_bib17","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1039\/C4MB00741G","article-title":"An integrated analysis of differential miRNA and mRNA expressions in human gallstones","volume":"11","author":"Yang","year":"2015","journal-title":"Mol. Biosyst."},{"key":"10.1016\/j.ijsu.2018.03.053_bib18","first-page":"1849","article-title":"miR-1 and miR-145 act as tumor suppressor microRNAs in gallbladder cancer","volume":"7","author":"Letelier","year":"2014","journal-title":"Int. J. Clin. Exp. Pathol."},{"issue":"3","key":"10.1016\/j.ijsu.2018.03.053_bib19","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1007\/s00535-005-1752-3","article-title":"Promoter methylation profile in gallbladder cancer","volume":"41","author":"Roa","year":"2006","journal-title":"J. Gastroenterol."},{"issue":"1","key":"10.1016\/j.ijsu.2018.03.053_bib20","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1002\/mc.20457","article-title":"Promoter methylation profile in preneoplastic and neoplastic gallbladder lesions","volume":"48","author":"Garc\u00eda","year":"2009","journal-title":"Mol. Carcinog."},{"issue":"4","key":"10.1016\/j.ijsu.2018.03.053_bib21","first-page":"451","article-title":"Gene methylation patterns in digestive tumors","volume":"136","author":"Roa","year":"2008","journal-title":"Rev. Med. Chile"},{"issue":"2","key":"10.1016\/j.ijsu.2018.03.053_bib22","doi-asserted-by":"crossref","first-page":"233","DOI":"10.2217\/fon.14.165","article-title":"Global and gene-specific DNA methylation pattern discriminates cholecystitis from gallbladder cancer patients in Chile","volume":"11","author":"Kagohara","year":"2015","journal-title":"Future Oncol."},{"issue":"8","key":"10.1016\/j.ijsu.2018.03.053_bib23","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1245\/ASO.2003.02.014","article-title":"Progression of gene hypermethylation in gallstone disease leading to gallbladder cancer","volume":"10","author":"House","year":"2003","journal-title":"Ann. Surg Oncol."},{"issue":"6","key":"10.1016\/j.ijsu.2018.03.053_bib24","first-page":"1130","article-title":"Mutational analysis of the APC\/beta-catenin\/Tcf pathway in colorectal cancer","volume":"58","author":"Sparks","year":"1998","journal-title":"Canc. Res."},{"issue":"6","key":"10.1016\/j.ijsu.2018.03.053_bib25","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1046\/j.1365-3083.2000.00727.x","article-title":"Recruitment of SHP-1 protein tyrosine phosphatase and signalling by a chimeric T-cell receptor-killer inhibitory receptor","volume":"51","author":"Christensen","year":"2000","journal-title":"Scand. J. Immunol."},{"key":"10.1016\/j.ijsu.2018.03.053_bib26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0378-1119(03)00400-1","article-title":"The function of the protein tyrosine phosphatase SHP-1 in cancer","volume":"306","author":"Wu","year":"2003","journal-title":"Gene"},{"issue":"5","key":"10.1016\/j.ijsu.2018.03.053_bib27","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1369\/jhc.2009.953026","article-title":"Analysis of DNA methylation of multiple genes in microdissected cells from formalin-fixed and paraffin-embedded tissues","volume":"57","author":"Dietrich","year":"2009","journal-title":"J. Histochem. Cytochem."},{"issue":"5","key":"10.1016\/j.ijsu.2018.03.053_bib28","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1245\/ASO.2005.07.020","article-title":"Tumor progression through epigenetic gene silencing of O(6)-methylguanine-DNA methyltransferase in human biliary tract cancers","volume":"12","author":"Koga","year":"2005","journal-title":"Ann. Surg Oncol."},{"issue":"6","key":"10.1016\/j.ijsu.2018.03.053_bib29","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1007\/s12282-015-0665-0","article-title":"A study on promoter methylation of PTEN in sporadic breast cancer patients from North India","volume":"23","author":"Siddiqui","year":"2016","journal-title":"Breast Canc."},{"issue":"2","key":"10.1016\/j.ijsu.2018.03.053_bib30","doi-asserted-by":"crossref","first-page":"192","DOI":"10.3748\/wjg.v12.i2.192","article-title":"Alterations of tumor suppressor and tumor-related genes in the development and progression of gastric cancer","volume":"12","author":"Tamura","year":"2006","journal-title":"World J. Gastroenterol."},{"issue":"12","key":"10.1016\/j.ijsu.2018.03.053_bib31","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/j.cancergen.2015.09.007","article-title":"Effects of PTEN gene alteration in patients with gallbladder cancer","volume":"208","author":"Ali","year":"2015","journal-title":"Cancer Genet."},{"issue":"1","key":"10.1016\/j.ijsu.2018.03.053_bib32","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1007\/s12029-017-9919-8","article-title":"Epigenetic downregulation of PTEN in gallbladder cancer","volume":"48","author":"Tekcham","year":"2017","journal-title":"J. Gastrointest. Canc."},{"key":"10.1016\/j.ijsu.2018.03.053_bib33","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.ebiom.2016.04.017","article-title":"Implications of genetic and epigenetic alterations of CDKN2A (p16(INK4a)) in cancer","volume":"8","author":"Zhao","year":"2016","journal-title":"EBioMedicine"},{"issue":"47","key":"10.1016\/j.ijsu.2018.03.053_bib34","doi-asserted-by":"crossref","first-page":"6396","DOI":"10.3748\/wjg.v13.i47.6396","article-title":"Two distinct pathways of p16 gene inactivation in gallbladder cancer","volume":"13","author":"Tadokoro","year":"2007","journal-title":"World J. Gastroenterol."},{"issue":"9","key":"10.1016\/j.ijsu.2018.03.053_bib35","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1111\/j.1349-7006.2004.tb03254.x","article-title":"Promoter hypermethylation of DAP-kinase is associated with poor survival in primary biliary tract carcinoma patients","volume":"95","author":"Tozawa","year":"2004","journal-title":"Canc. Sci."},{"issue":"11","key":"10.1016\/j.ijsu.2018.03.053_bib36","first-page":"1369","article-title":"Inactivation of CDKN2A gene (p16) in gallbladder carcinoma","volume":"132","author":"Roa","year":"2004","journal-title":"Rev. Med. Chile"},{"issue":"5","key":"10.1016\/j.ijsu.2018.03.053_bib37","first-page":"1773","article-title":"Promoter methylation of INK4a\/ARF as detected in bile-significance for the differential diagnosis in biliary disease","volume":"9","author":"Klump","year":"2003","journal-title":"Clin. Canc. Res."},{"issue":"5","key":"10.1016\/j.ijsu.2018.03.053_bib38","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.1158\/1078-0432.CCR-1137-3","article-title":"Alterations of p16 and prognosis in biliary tract cancers from a population-based study in China","volume":"10","author":"Ueki","year":"2004","journal-title":"Clin. Canc. Res."},{"issue":"5\u20136","key":"10.1016\/j.ijsu.2018.03.053_bib39","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1387\/ijdb.041815jb","article-title":"The Wnt connection to tumorigenesis","volume":"48","author":"Behrens","year":"2004","journal-title":"Int. J. Dev. Biol."},{"issue":"3","key":"10.1016\/j.ijsu.2018.03.053_bib40","doi-asserted-by":"crossref","first-page":"2573","DOI":"10.3892\/mmr.2016.5532","article-title":"Rescued expression of WIF-1 in gallbladder cancer inhibits tumor growth and induces tumor cell apoptosis with altered expression of proteins","volume":"14","author":"Huang","year":"2016","journal-title":"Mol. Med. Rep."},{"key":"10.1016\/j.ijsu.2018.03.053_bib41","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.gene.2017.04.034","article-title":"WNT inhibitory factor 1 promoter hypermethylation is an early event during gallbladder cancer tumorigenesis that predicts poor survival","volume":"622","author":"Lin","year":"2017","journal-title":"Gene"},{"issue":"1","key":"10.1016\/j.ijsu.2018.03.053_bib42","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.canlet.2006.09.019","article-title":"Frequent epigenetic inactivation of chromosome 3p candidate tumor suppressor genes in gallbladder carcinoma","volume":"250","author":"Riquelme","year":"2007","journal-title":"Canc. Lett."},{"issue":"3","key":"10.1016\/j.ijsu.2018.03.053_bib43","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/S1016-8478(23)07352-1","article-title":"Hypermethylation of the Ras association domain family 1A (RASSF1A) gene in gallbladder cancer","volume":"24","author":"Kee","year":"2007","journal-title":"Mol. Cell."},{"issue":"11","key":"10.1016\/j.ijsu.2018.03.053_bib44","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1111\/j.1349-7006.2006.00320.x","article-title":"Hypomethylation of the protein gene product 9.5 promoter region in gallbladder cancer and its relationship with clinicopathological features","volume":"97","author":"Lee","year":"2006","journal-title":"Canc. Sci."},{"issue":"11","key":"10.1016\/j.ijsu.2018.03.053_bib45","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0188178","article-title":"Prognostic significance of promoter DNA hypermethylation of the cysteine dioxygenase 1 (CDO1) gene in primary gallbladder cancer and gallbladder disease","volume":"12","author":"Igarashi","year":"2017","journal-title":"PLoS One"},{"issue":"1","key":"10.1016\/j.ijsu.2018.03.053_bib46","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/1868-7083-4-11","article-title":"DNA promoter methylation as a diagnostic and therapeutic biomarker in gallbladder cancer","volume":"4","author":"Letelier","year":"2012","journal-title":"Clin. Epigenet."},{"key":"10.1016\/j.ijsu.2018.03.053_bib47","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.amjsurg.2007.11.011","article-title":"Gallbladder cancer","volume":"196","author":"Gourgiotis","year":"2008","journal-title":"Am. J. Surg."},{"key":"10.1016\/j.ijsu.2018.03.053_bib48","doi-asserted-by":"crossref","DOI":"10.1053\/gast.1996.v111.pm8698204","article-title":"Preneoplastic lesions and gallbladder cancer: an estimate of the period required for progression","volume":"111","author":"Roa","year":"1996","journal-title":"Gastroenterology"},{"key":"10.1016\/j.ijsu.2018.03.053_bib49","article-title":"Gallbladder cancer in high risk area: morphological features and spread patterns","volume":"46","author":"Roa","year":"1999","journal-title":"Hepato-Gastroenterology"},{"key":"10.1016\/j.ijsu.2018.03.053_bib50","doi-asserted-by":"crossref","first-page":"266","DOI":"10.2353\/jmoldx.2009.080125","article-title":"CpG methylation analysis\u2013current status of clinical assays and potential applications in molecular diagnostics: a report of the association for molecular pathology","volume":"11","author":"Sepulveda","year":"2009","journal-title":"J. Mol. Diagn."},{"key":"10.1016\/j.ijsu.2018.03.053_bib51","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1111\/j.1477-2574.2011.00303.x","article-title":"Clinical implications of DNA methylation in hepatocellular carcinoma","volume":"13","author":"Sceusi","year":"2011","journal-title":"HPB"},{"key":"10.1016\/j.ijsu.2018.03.053_bib52","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1358\/dot.2007.43.6.1062666","article-title":"DNA methyltransferases as targets for cancer therapy","volume":"43","author":"Ghoshal","year":"2007","journal-title":"Drugs Today"}],"container-title":["International Journal of Surgery"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1743919118306526?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1743919118306526?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.ovid.com\/10.1016\/j.ijsu.2018.03.053","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T12:25:34Z","timestamp":1789647934000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.1016\/j.ijsu.2018.03.053"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,5]]},"references-count":52,"alternative-id":["S1743919118306526"],"URL":"https:\/\/doi.org\/10.1016\/j.ijsu.2018.03.053","relation":{},"ISSN":["1743-9191"],"issn-type":[{"value":"1743-9191","type":"print"}],"subject":[],"published":{"date-parts":[[2018,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"DNA methylation as an epigenetic regulator of gallbladder cancer: An overview","name":"articletitle","label":"Article Title"},{"value":"International Journal of Surgery","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ijsu.2018.03.053","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2018 IJS Publishing Group Ltd. Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}]}}