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dc.contributor.authorKelly, Z.*
dc.contributor.authorMoller-Levet, C.*
dc.contributor.authorMcGrath, S.*
dc.contributor.authorButler-Manuel, S.*
dc.contributor.authorMadhuri, T.K.*
dc.contributor.authorKierzek, A.M.*
dc.contributor.authorPandha, H.S.*
dc.contributor.authorMorgan, Richard*
dc.contributor.authorMichael, A.*
dc.date.accessioned2016-10-13T14:56:39Z
dc.date.available2016-10-13T14:56:39Z
dc.date.issued2016-10-01
dc.identifier.citationKelly Z, Moller-Levet C, McGrath S et al. (2016) The prognostic significance of specific HOX gene expression patterns in ovarian cancer. International Journal of Cancer. 139(7): 1608-1617.en_US
dc.identifier.urihttp://hdl.handle.net/10454/9921
dc.descriptionYesen_US
dc.description.abstractHOX 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 HOX 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 con-text of platinum resistance. HOX 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-way ANOVA and t-tests, using statistical software R and GraphPad. The analysis identified 36 of the 39 HOX genes as being overex-pressed in high grade serous EOC compared to normal tissue. We detected a molecular HOX gene-signature that predicted poor outcome. Overexpression of HOXB4 and HOXB9 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-resistant ovarian cancer. In conclusion, this study has shown the HOX genes are highly dysregulated in ovarian cancer with high expression of HOXA13, B6, C13, D1 and D13 being predictive of poor clinical outcome. Targeting the HOX/PBX dimer in platinum–resistant cancer represents a potentially new therapeutic option that should be further developed and tested in clinical trials.en_US
dc.description.sponsorshipThis research was supported by GRACE, a gynaecological charity based in Surrey, UK.en_US
dc.language.isoenen_US
dc.relation.isreferencedbyhttp://dx.doi.org/10.1002/ijc.30204en_US
dc.rights© 2016 The Authors International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.en_US
dc.subjectOvarian cancer; HOX genes; Survival; Prognosis; Targeted treatmenten_US
dc.titleThe prognostic significance of specific HOX gene expression patterns in ovarian canceren_US
dc.status.refereedYesen_US
dc.date.Accepted2016-04-25
dc.date.application2016-05-25
dc.typeArticleen_US
dc.type.versionAccepted Manuscripten_US
refterms.dateFOA2018-07-27T01:37:46Z


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