{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:21:05Z","timestamp":1787725265430,"version":"build-2784847793"},"reference-count":46,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2016,6,14]],"date-time":"2016-06-14T00:00:00Z","timestamp":1465862400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2016,10]]},"abstract":"<jats:p><jats:italic>HOX<\/jats:italic> genes are vital for all aspects of mammalian growth and differentiation, and their dysregulated expression is related to ovarian carcinogenesis. The aim of the current study was to establish the prognostic value of <jats:italic>HOX<\/jats:italic> dysregulation as well as its role in platinum resistance. The potential to target HOX proteins through the HOX\/PBX interaction was also explored in the context of platinum resistance. <jats:italic>HOX<\/jats:italic> gene expression was determined in ovarian cancer cell lines and primary EOCs by QPCR, and compared to expression in normal ovarian epithelium and fallopian tube tissue samples. Statistical analysis included one\u2010way ANOVA and <jats:italic>t<\/jats:italic>\u2010tests, using statistical software R and GraphPad. The analysis identified 36 of the 39 <jats:italic>HOX<\/jats:italic> genes as being overexpressed in high grade serous EOC compared to normal tissue. We detected a molecular <jats:italic>HOX<\/jats:italic> gene\u2010signature that predicted poor outcome. Overexpression of <jats:italic>HOXB4<\/jats:italic> and <jats:italic>HOXB9<\/jats:italic> was identified in high grade serous cell lines after platinum resistance developed. Targeting the HOX\/PBX dimer with the HXR9 peptide enhanced the cytotoxicity of cisplatin in platinum\u2010resistant ovarian cancer. In conclusion, this study has shown the <jats:italic>HOX<\/jats:italic> genes are highly dysregulated in ovarian cancer with high expression of <jats:italic>HOXA13<\/jats:italic>, <jats:italic>B6<\/jats:italic>, <jats:italic>C13<\/jats:italic>, <jats:italic>D1<\/jats:italic> and <jats:italic>D13<\/jats:italic> being predictive of poor clinical outcome. Targeting the HOX\/PBX dimer in platinum\u2013resistant cancer represents a potentially new therapeutic option that should be further developed and tested in clinical trials.<\/jats:p>","DOI":"10.1002\/ijc.30204","type":"journal-article","created":{"date-parts":[[2016,5,26]],"date-time":"2016-05-26T12:04:12Z","timestamp":1464264252000},"page":"1608-1617","source":"Crossref","is-referenced-by-count":57,"title":["The prognostic significance of specific <i>HOX<\/i> gene expression patterns in ovarian cancer"],"prefix":"10.1002","volume":"139","author":[{"given":"Zoe","family":"Kelly","sequence":"first","affiliation":[{"name":"Oncology, School of Biosciences and Medicine FHMS, Leggett Building, Daphne Jackson Road, University of Surrey Guildford GU2 7WG"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Moller\u2010Levet","sequence":"additional","affiliation":[{"name":"Computational &amp; Systems Biology, School of Biosciences and Medicine FHMS, University of Surrey Guildford GU2 7TE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"McGrath","sequence":"additional","affiliation":[{"name":"Oncology, School of Biosciences and Medicine FHMS, Leggett Building, Daphne Jackson Road, University of Surrey Guildford GU2 7WG"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Butler\u2010Manuel","sequence":"additional","affiliation":[{"name":"Royal Surrey County Hospital Egerton Road Guildford GU2 7XX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thumuluru","family":"Kavitha Madhuri","sequence":"additional","affiliation":[{"name":"Royal Surrey County Hospital Egerton Road Guildford GU2 7XX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrzej M.","family":"Kierzek","sequence":"additional","affiliation":[{"name":"Computational &amp; Systems Biology, School of Biosciences and Medicine FHMS, University of Surrey Guildford GU2 7TE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hardev","family":"Pandha","sequence":"additional","affiliation":[{"name":"Oncology, School of Biosciences and Medicine FHMS, Leggett Building, Daphne Jackson Road, University of Surrey Guildford GU2 7WG"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Morgan","sequence":"additional","affiliation":[{"name":"ICT Building, Institute of Cancer Therapeutics, University of Bradford West Yorkshire BD7 1DP"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Michael","sequence":"additional","affiliation":[{"name":"Oncology, School of Biosciences and Medicine FHMS, Leggett Building, Daphne Jackson Road, University of Surrey Guildford GU2 7WG"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,6,14]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.20138"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.011503998"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1230"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod57.6.1338"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/1757-2215-4-16"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.23.12776"},{"key":"e_1_2_7_8_1","first-page":"5879","article-title":"Aberrant HOXC expression accompanies the malignant phenotype in human prostate","volume":"63","author":"Miller GJ","year":"2003","journal-title":"Cancer Res"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/35016125"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1997.6364"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10166"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-4231"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6604857"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-10-89"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2008.07.018"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-012-2259-2"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3126"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-10-4111"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.6.10.986"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.58.3.10"},{"key":"e_1_2_7_21_1","unstructured":"WorkmanP TP BalkwillF BalmainA ChaplinD DoubleJ EmbletonJ NewellD RaymondR StablesJ StephensT WallaceJ.United Kingdom Co\u2010ordinating Committee on Cancer Research (UKCCCR) guidelines for the welfare of animals in experimental neoplasia.1998."},{"key":"e_1_2_7_22_1","first-page":"6166","article-title":"Characterization and Properties of Nine Human Ovarian Adenocarcinoma Cell Lines","volume":"48","author":"Langdon SP","year":"1988","journal-title":"Cancer Res"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2007.08.025"},{"key":"e_1_2_7_24_1","first-page":"23","article-title":"HOX genes: seductive science, mysterious mechanisms","volume":"75","author":"Lappin TRJ","year":"2006","journal-title":"The Ulster Medical Journal"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1177\/1933719107307781"},{"key":"e_1_2_7_26_1","first-page":"931","article-title":"Suppression of invasive characteristics by antisense introduction of overexpressed HOX genes in ovarian cancer cells","volume":"28","author":"Yamashita T","year":"2006","journal-title":"Int J Oncol"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.071594398"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-4283"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0707938104"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.3802\/jgo.2010.21.1.29"},{"key":"e_1_2_7_31_1","first-page":"3281","article-title":"Immunocytochemical detection of the homeobox B3, B4, and C6 gene products in breast carcinomas","volume":"20","author":"Bodey B","year":"2000","journal-title":"Anticancer Res"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI34371"},{"key":"e_1_2_7_33_1","first-page":"2711","article-title":"Immunocytochemical detection of homeobox B3, B4, and C6 gene product expression in lung carcinomas","volume":"20","author":"Bodey B","year":"2000","journal-title":"Anticancer Res"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10166"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature03648"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-4546"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12032-013-0564-1"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.25941"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.10900"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.8.3.7649"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5876-10-91"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.10139"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1159\/000217965"},{"key":"e_1_2_7_44_1","first-page":"673","article-title":"Aberrant expression of HOX genes in human invasive breast carcinoma","volume":"13","author":"Makiyama K","year":"2005","journal-title":"Oncol Rep"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1525-1438.2006.00603.x"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.20706"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.24438"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fijc.30204","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.30204","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T16:31:59Z","timestamp":1695573119000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.30204"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,6,14]]},"references-count":46,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2016,10]]}},"alternative-id":["10.1002\/ijc.30204"],"URL":"https:\/\/doi.org\/10.1002\/ijc.30204","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,6,14]]}}}