{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T04:35:58Z","timestamp":1729226158324,"version":"3.27.0"},"reference-count":36,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":67,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"name":"Bundesministerium f\u00fcr Wirtschaft und Technologie, Germany","award":["SIGNO program 03VWP0033"],"award-info":[{"award-number":["SIGNO program 03VWP0033"]}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2015,9]]},"abstract":"<jats:p>Curative treatment of intrahepatic cholangiocarcinoma (ICC) and hilar cholangiocarcinoma (Klatskin tumors) is limited to surgical resection or orthotopic liver transplantation. However, not all patients benefit from a surgical approach and suffer from early tumor recurrence. Response to chemotherapy is generally poor and, until today, no targeted therapy could be established. Metastasis\u2010associated in colon cancer 1 (MACC1) is a recently discovered regulator of the hepatocyte growth factor (HGF)\/Met\/mitogen\u2010activated protein kinase pathway, which induces proliferation, migration, and invasion in cell culture, as well as metastasis in mice. MACC1 expression shows a significant correlation with Met expression in colon cancer tissue and is highly prognostic for occurrence of distant metastasis and survival in colon cancer patients. Thus, we aimed to measure the expression of MACC1, Met, and HGF messenger RNA in microdissected tumor tissue and corresponding normal liver tissue of 156 patients with Klatskin tumors (n\u2009=\u200976) and ICC (n\u2009=\u200980) using real\u2010time quantitative reverse\u2010transcriptase polymerase chain reaction. We used immunohistochemical staining to validate the results. MACC1 expression in tumor tissue of both tumor entities was significantly higher than in corresponding normal liver tissue (<jats:italic toggle=\"yes\">P<\/jats:italic>\u2009&lt;\u20090.001). Klatskin tumor patients with a history of tumor recurrence had significantly higher MACC1 expression than those without tumor recurrence (<jats:italic toggle=\"yes\">P<\/jats:italic>\u2009=\u20090.005). Uni\u2010 und multivariate survival analysis showed that Klatskin tumor patients with high MACC1 had a significantly shorter overall (OS) and disease\u2010free survival (DFS; <jats:italic toggle=\"yes\">P<\/jats:italic>\u2009=\u20090.001 and <jats:italic toggle=\"yes\">P<\/jats:italic>\u2009&lt;\u20090.001, respectively). The multivariate analysis confirmed MACC1 to be an independent factor for overall survival in Klatskin tumor patients (hazard ratio: 2.777; 95% confidence interval: 1.389\u20105.555; <jats:italic toggle=\"yes\">P<\/jats:italic>\u2009=\u20090.004). <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic> Our study identified MACC1 as a highly prognostic biomarker for OS and DFS in Klatskin tumor patients. MACC1 expression could become an important diagnostic tool and might be a candidate for targeted therapy. (H<jats:sc>epatology<\/jats:sc> 2015;62:841\u2013850)<\/jats:p>","DOI":"10.1002\/hep.27885","type":"journal-article","created":{"date-parts":[[2015,5,8]],"date-time":"2015-05-08T08:09:57Z","timestamp":1431072597000},"page":"841-850","update-policy":"http:\/\/dx.doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":20,"title":["Metastasis\u2010associated in colon cancer 1 is an independent prognostic biomarker for survival in klatskin tumor patients"],"prefix":"10.1097","volume":"62","author":[{"given":"Andri","family":"Lederer","sequence":"first","affiliation":[{"name":"Experimental and Clinical Research Center,Charit\u00e9 Universit\u00e4tsmedizin Berlin, and Max\u2010Delbr\u00fcck\u2010Center for Molecular Medicine,Berlin,Germany"},{"name":"Department of General\u2010, Visceral\u2010 and Transplant Surgery,Charit\u00e9 Universit\u00e4tsmedizin Berlin, Campus Virchow,Berlin,Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pia","family":"Herrmann","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Research Center,Charit\u00e9 Universit\u00e4tsmedizin Berlin, and Max\u2010Delbr\u00fcck\u2010Center for Molecular Medicine,Berlin,Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Seehofer","sequence":"additional","affiliation":[{"name":"Department of General\u2010, Visceral\u2010 and Transplant Surgery,Charit\u00e9 Universit\u00e4tsmedizin Berlin, Campus Virchow,Berlin,Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manfred","family":"Dietel","sequence":"additional","affiliation":[{"name":"Department of Pathology,Charit\u00e9 Universit\u00e4tsmedizin Berlin,Campus Mitte,Berlin,Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johann","family":"Pratschke","sequence":"additional","affiliation":[{"name":"Department of General\u2010, Visceral\u2010 and Transplant Surgery,Charit\u00e9 Universit\u00e4tsmedizin Berlin, Campus Virchow,Berlin,Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Schlag","sequence":"additional","affiliation":[{"name":"Charit\u00e9 Comprehensive Cancer Center,Charit\u00e9 Universit\u00e4tsmedizin Berlin, Campus Mitte, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrike","family":"Stein","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Research Center,Charit\u00e9 Universit\u00e4tsmedizin Berlin, and Max\u2010Delbr\u00fcck\u2010Center for Molecular Medicine,Berlin,Germany"},{"name":"German Cancer Consortium,Heidelberg,Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","published-online":{"date-parts":[[2015,6,26]]},"reference":[{"key":"hep27885-bib-0001-20241017","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1038\/nrgastro.2011.20","article-title":"Cholangiocarcinoma\u2010controversies and challenges","volume":"8","year":"2011","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"hep27885-bib-0002-20241017","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1055\/s-2004-828889","article-title":"The epidemiology of cholangiocarcinoma","volume":"24","year":"2004","journal-title":"Semin Liver Dis"},{"key":"hep27885-bib-0003-20241017","doi-asserted-by":"crossref","first-page":"S5","DOI":"10.1053\/j.gastro.2004.09.011","article-title":"Primary liver cancer: worldwide incidence and 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