Clinicopathological and prognostic significance of RECQL5 helicase expression in breast cancers

Arora, A., Abdel-Fatah, T.M.A., Agarwal, D., Doherty, R., Croteau, D.L., Moseley, P.M., Hameed, K., Green, A., Aleskandarany, M.A., Rakha, E.A., Patterson, K., Ball, G. ORCID: 0000-0001-5828-7129, Chan, S.Y.T., Ellis, I.O., Bohr, V.A., Bryant, H.E. and Madhusudan, S., 2015. Clinicopathological and prognostic significance of RECQL5 helicase expression in breast cancers. Carcinogenesis, 37 (1), pp. 63-71. ISSN 0143-3334

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Abstract

RECQL5 is a member of the RecQ family of DNA helicases and has key roles in homologous recombination, base excision repair, replication and transcription. The clinicopathological significance of RECQL5 expression in breast cancer is unknown. In the current study we have evaluated RECQL5 mRNA expression in 1977 breast cancers, and RECQL5 protein level in 1902 breast cancers [Nottingham Tenovus series (n=1650) and ER- cohort (n=252)]. Expression levels were correlated to aggressive phenotypes and survival outcomes. High RECQL5 mRNA expression was significantly associated with high histological grade (p=0.007), HER2 overexpression (p=0.032), ER+/HER2-/high proliferation genefu subtype, integrative molecular clusters (intClust 1and 9) and poor breast cancer specific survival (BCSS) (ps<0.0001). In sub-group analysis, high RECQL5 mRNA level remains significantly associated with poor BCSS in ER+ cohort (p<0.0001) but not in ER- cohort (p=0.116). At the protein level, in tumours with low RAD51, high RECQL5 level was significantly associated with high histological grade (p<0.0001), higher mitotic index (p=0.008), de-differentiation (p=0.025), pleomorphism (p=0.027) and poor BCSS (P=0.003). In sub-group analysis, high RECQL5/low RAD51 remains significantly associated with poor BCSS in ER+ cohort (p=0.010), but not in ER- cohort (p=0.628). In multivariate analysis, high RECQL5 mRNA and high RECQL5/low RAD51 nuclear protein co-expression independently influenced BCSS (p=0.022) in whole cohort and in the ER+ sub-group. Pre-clinically, we show that exogenous expression of RECQL5 in MCF10A cells can drive proliferation supporting an oncogenic function for RECQL5 in breast cancer. We conclude that RECQL5 is a promising biomarker in breast cancer.

Item Type: Journal article
Publication Title: Carcinogenesis
Creators: Arora, A., Abdel-Fatah, T.M.A., Agarwal, D., Doherty, R., Croteau, D.L., Moseley, P.M., Hameed, K., Green, A., Aleskandarany, M.A., Rakha, E.A., Patterson, K., Ball, G., Chan, S.Y.T., Ellis, I.O., Bohr, V.A., Bryant, H.E. and Madhusudan, S.
Publisher: Oxford University Press
Date: 2015
Volume: 37
Number: 1
ISSN: 0143-3334
Identifiers:
NumberType
10.1093/carcin/bgv163DOI
Divisions: Schools > School of Science and Technology
Depositing User: Jonathan Gallacher
Date Added: 09 Feb 2016 15:02
Last Modified: 09 Jun 2017 13:59
URI: http://irep.ntu.ac.uk/id/eprint/26917

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