University of Surrey

Test tubes in the lab Research in the ATI Dance Research

The prognostic significance of specific HOX gene expression patterns in ovarian cancer

Kelly, Z, Moller-Levet, C, McGrath, S, Butler-Manuel, S, Madhuri, TK, Kierzek, AM, Pandha, HS, Morgan, R and Michael, A (2016) The prognostic significance of specific HOX gene expression patterns in ovarian cancer International Journal of Cancer, 139 (7). pp. 1608-1617.

[img]
Preview
Text
Kelly_et_al-2016-International_Journal_of_Cancer.pdf - Version of Record

Download (720kB) | Preview
[img] Text
July 2014 Pattern of HOX gene expression in ovarian cancer v4.doc - Accepted version Manuscript
Restricted to Repository staff only
Available under License : See the attached licence file.

Download (221kB)
[img] Text
Figure 1a.docx - Accepted version Manuscript
Restricted to Repository staff only
Available under License : See the attached licence file.

Download (113kB)
[img] Text
Figure 6.docx - Accepted version Manuscript
Restricted to Repository staff only
Available under License : See the attached licence file.

Download (75kB)
[img] Text
Figure 5.docx - Accepted version Manuscript
Restricted to Repository staff only
Available under License : See the attached licence file.

Download (39kB)
[img] Text
Figure 4 a b.docx - Accepted version Manuscript
Restricted to Repository staff only
Available under License : See the attached licence file.

Download (65kB)
[img] Text
Figure 3.docx - Accepted version Manuscript
Restricted to Repository staff only
Available under License : See the attached licence file.

Download (55kB)
[img] Text
Table 1.docx - Accepted version Manuscript
Restricted to Repository staff only
Available under License : See the attached licence file.

Download (14kB)
[img] Text
Figure 2.docx - Accepted version Manuscript
Restricted to Repository staff only
Available under License : See the attached licence file.

Download (48kB)
[img] Text
Figure 1 b.docx - Accepted version Manuscript
Restricted to Repository staff only
Available under License : See the attached licence file.

Download (32kB)
[img] Text
Table 3.docx - Accepted version Manuscript
Restricted to Repository staff only
Available under License : See the attached licence file.

Download (14kB)
[img]
Preview
Text (licence)
SRI_deposit_agreement.pdf
Available under License : See the attached licence file.

Download (33kB) | Preview

Abstract

OBJECTIVE: HOX 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 context of platinum resistance. METHODS: HOX gene expression was determined in ovarian cancer cell lines and primary EOCs, 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. RESULTS: 30 of the 39 HOX genes were overexpressed in high grade serous EOC compared to normal tissue, most significant being HOXA3, A9, B13 and C10. 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 the HXR9 peptide enhanced the cytotoxicity of cisplatin in platinum-resistant ovarian cancer.CONCLUSIONS: HOX genes are highly dysregulated in ovarian cancer. High expression of HOXA13, B6, C13, D1 and D13 is predictive of poor clinical outcome. Targeting the HOX/PBX dimer in platinum–resistant cancer represents a new therapeutic option that should be further developed and tested in clinical trials.

Item Type: Article
Subjects : Biosciences and Medicine
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
AuthorsEmailORCID
Kelly, ZUNSPECIFIEDUNSPECIFIED
Moller-Levet, CUNSPECIFIEDUNSPECIFIED
McGrath, SUNSPECIFIEDUNSPECIFIED
Butler-Manuel, SUNSPECIFIEDUNSPECIFIED
Madhuri, TKUNSPECIFIEDUNSPECIFIED
Kierzek, AMUNSPECIFIEDUNSPECIFIED
Pandha, HSUNSPECIFIEDUNSPECIFIED
Morgan, RUNSPECIFIEDUNSPECIFIED
Michael, AUNSPECIFIEDUNSPECIFIED
Date : 14 June 2016
Identification Number : 10.1002/ijc.30204
Copyright Disclaimer : Copyright 2016 The Authors. 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.
Uncontrolled Keywords : Ovarian cancer, HOX genes, survival, prognosis, targeted treatment
Related URLs :
Depositing User : Symplectic Elements
Date Deposited : 06 Sep 2016 11:33
Last Modified : 30 Nov 2016 18:23
URI: http://epubs.surrey.ac.uk/id/eprint/811987

Actions (login required)

View Item View Item

Downloads

Downloads per month over past year


Information about this web site

© The University of Surrey, Guildford, Surrey, GU2 7XH, United Kingdom.
+44 (0)1483 300800