{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:32:02Z","timestamp":1791351122432,"version":"4.3.1"},"reference-count":31,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2009,1,21]],"date-time":"2009-01-21T00:00:00Z","timestamp":1232496000000},"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":[[2009,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Recently, the copper efflux transporters ATP7B and ATP7A have been implicated in the transport of and resistance to platinum drugs in breast and ovarian cancers. Because of the extensive use of oxaliplatin in colorectal cancer (CRC), we examined the expression of both transporters in tumors from CRC patients treated with oxaliplatin\/5FU and sought to determine whether their expression can predict clinical outcome in these patients. ATP7B and ATP7A levels were determined by quantitative real\u2010time PCR in 50 primary tumors of previously untreated patients with advanced colorectal adenocarcinoma who were subsequently treated with oxaliplatin\/5FU. Additionally, ATP7B protein expression was assessed by immunohistochemical staining using a tissue microarray. Patients with the lowest mRNA expression levels of ATP7B had a significantly longer time to progression (TTP) (<jats:italic>p<\/jats:italic> = 0.0009) than patients with the highest levels (12.14 months <jats:italic>vs<\/jats:italic>. 6.43 months) who also had an increased risk of progression (HR = 3.56; 95% CI, 1.6\u20137.9; <jats:italic>p<\/jats:italic> = 0.002). Furthermore, patients with low levels of both protein and mRNA of ATP7B derived the maximum benefit from oxaliplatin\/5FU with the longest TTP as compared with patients with high levels of ATP7B protein and mRNA (14.64 months <jats:italic>vs<\/jats:italic>. 4.63 months, respectively, <jats:italic>p<\/jats:italic> = 0.01) and showed a nonsignificant trend toward a lower response rate (37.5% and 75%, respectively). In conclusion, ATP7B mRNA and protein expression in colorectal tumors is associated with clinical outcome to oxaliplatin\/5FU. Prospective studies are required to evaluate the role of this marker in tailoring chemotherapy. \u00a9 2009 UICC<\/jats:p>","DOI":"10.1002\/ijc.24273","type":"journal-article","created":{"date-parts":[[2009,1,21]],"date-time":"2009-01-21T16:25:08Z","timestamp":1232555108000},"page":"2905-2910","source":"Crossref","is-referenced-by-count":64,"title":["Increased levels of copper efflux transporter ATP7B are associated with poor outcome in colorectal cancer patients receiving oxaliplatin\u2010based chemotherapy"],"prefix":"10.1002","volume":"124","author":[{"given":"Eva","family":"Martinez\u2010Balibrea","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Mart\u00ednez\u2010Card\u00fas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Musul\u00e9n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alba","family":"Gin\u00e9s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Luis","family":"Manzano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrique","family":"Aranda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Plasencia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nouri","family":"Neamati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Abad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,3,18]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2167"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2006.09.006"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-2238"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-08-0659"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0027-5107(01)00141-5"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/134.5.1003"},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.14.7481"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/129.7.1251"},{"key":"e_1_2_5_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-003-1092-1"},{"key":"e_1_2_5_11_2","first-page":"1312","article-title":"Copper\u2010transporting P\u2010type adenosine triphosphatase (ATP7B) is associated with cisplatin resistance","volume":"60","author":"Komatsu M","year":"2000","journal-title":"Cancer Res"},{"key":"e_1_2_5_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2005.07.046"},{"key":"e_1_2_5_13_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.107.040980"},{"key":"e_1_2_5_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinorgbio.2004.05.006"},{"key":"e_1_2_5_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.10608"},{"key":"e_1_2_5_16_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-03-0454"},{"key":"e_1_2_5_17_2","first-page":"5853","article-title":"Increase in expression of the copper transporter ATP7A during platinum drug\u2010based treatment is associated with poor survival in ovarian cancer patients","volume":"9","author":"Samimi G","year":"2003","journal-title":"Clin Cancer Res"},{"key":"e_1_2_5_18_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-03-0689"},{"key":"e_1_2_5_19_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-007-0640-3"},{"key":"e_1_2_5_20_2","first-page":"225","article-title":"Expression analysis of genes involved in oxaliplatin response and development of oxaliplatin\u2010resistant HT29 colon cancer cells","volume":"29","author":"Plasencia C","year":"2006","journal-title":"Int J Oncol"},{"key":"e_1_2_5_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddh260"},{"key":"e_1_2_5_22_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-04-0137"},{"key":"e_1_2_5_23_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2007.07.020"},{"key":"e_1_2_5_24_2","first-page":"2298","article-title":"Proteomic analysis of lung adenocarcinoma: identification of a highly expressed set of proteins in tumors","volume":"8","author":"Chen G","year":"2002","journal-title":"Clin Cancer Res"},{"key":"e_1_2_5_25_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-6770"},{"key":"e_1_2_5_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2004.12.042"},{"key":"e_1_2_5_27_2","first-page":"337","article-title":"Expression of copper\u2010transporting P\u2010type adenosine triphosphatase in human esophageal carcinoma","volume":"11","author":"Higashimoto M","year":"2003","journal-title":"Int J Mol Med"},{"key":"e_1_2_5_28_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2002.tb01202.x"},{"key":"e_1_2_5_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1368-8375(02)00038-6"},{"key":"e_1_2_5_30_2","first-page":"1285","article-title":"Expression and cisplatin sensitivity of copper\u2010transporting P\u2010type adenosine triphosphatase (ATP7B) in human solid carcinoma cell lines","volume":"8","author":"Nakayama K","year":"2001","journal-title":"Oncol Rep"},{"key":"e_1_2_5_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3835(02)00462-7"},{"key":"e_1_2_5_32_2","first-page":"1045","article-title":"Expression of copper\u2010transporting P\u2010type adenosine triphosphatase (ATP7B) in human hepatocellular carcinoma","volume":"24","author":"Sugeno H","year":"2004","journal-title":"Anticancer Res"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fijc.24273","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.24273","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,9]],"date-time":"2023-10-09T07:29:13Z","timestamp":1696836553000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.24273"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,3,18]]},"references-count":31,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2009,6,15]]}},"alternative-id":["10.1002\/ijc.24273"],"URL":"https:\/\/doi.org\/10.1002\/ijc.24273","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,3,18]]}}}