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Clinicopathological and prognostic significance of RECQL5 helicase expression in breast cancers

Arora, Arvind; Abdel-Fatah, Tarek M.A.; Agarwal, Devika; Doherty, Rachel; Croteau, Deborah L.; Moseley, Paul M.; Hameed, Khalid; Green, Andrew; Aleskandarany, Mohammed A.; Patterson, Karl; Rakha, Emad A.; Ball, Graham; Chan, Stephen Y.T.; Ellis, Ian O.; Bohr, Vilhelm A.; Bryant, Helen E.; Madhusudan, Srinivasan

Authors

Arvind Arora

Tarek M.A. Abdel-Fatah

Devika Agarwal

Rachel Doherty

Deborah L. Croteau

Paul M. Moseley

Khalid Hameed

Mohammed A. Aleskandarany

Karl Patterson

EMAD RAKHA Emad.Rakha@nottingham.ac.uk
Professor of Breast Cancer Pathology

Graham Ball

Stephen Y.T. Chan

Vilhelm A. Bohr

Helen E. Bryant



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 this 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 ( P < 0.0001), integrative molecular clusters (intClust 1and 9) ( P < 0.0001) and poor survival ( P < 0.0001). In subgroup 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), dedifferentiation ( P = 0.025), pleomorphism ( P = 0.027) and poor survival ( P = 0.003). In subgroup 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 coexpression independently influenced survival ( P = 0.022) in whole cohort and in the ER+ subgroup. Preclinically, 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.

Journal Article Type Article
Publication Date 2016-01
Journal Carcinogenesis
Print ISSN 0143-3334
Electronic ISSN 1460-2180
Publisher Oxford University Press (OUP)
Peer Reviewed Peer Reviewed
Volume 37
Issue 1
Pages 63-71
APA6 Citation Arora, A., Abdel-Fatah, T. M., Agarwal, D., Doherty, R., Croteau, D. L., Moseley, P. M., …Madhusudan, S. (2016). Clinicopathological and prognostic significance of RECQL5 helicase expression in breast cancers. Carcinogenesis, 37(1), 63-71. doi:10.1093/carcin/bgv163
DOI https://doi.org/10.1093/carcin/bgv163
Publisher URL https://academic.oup.com/carcin/article/37/1/63/2365822
Additional Information This is a pre-copyedited, author-produced version of an article accepted for publication in Carcinogenesis following peer review. The version of record Arvind Arora, Tarek M.A. Abdel-Fatah, Devika Agarwal, Rachel Doherty, Deborah L. Croteau, Paul M. Moseley, Khalid Hameed, Andrew Green, Mohammed A. Aleskandarany, Emad A. Rakha, Karl Patterson, Graham Ball, Stephen Y.T. Chan, Ian O. Ellis, Vilhelm A. Bohr, Helen E. Bryant, Srinivasan Madhusudan; Clinicopathological and prognostic significance of RECQL5 helicase expression in breast cancers, Carcinogenesis, Volume 37, Issue 1, 1 January 2016, Pages 63–71 is available online at: https://academic.oup.co...rticle/37/1/63/2365822.

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