Clinicopathological and prognostic significance of RECQL5 helicase expression in breast cancers.

Autor:	Arora A; Academic Unit of Oncology, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Nottingham NG51PB, UK, Department of Oncology, Nottingham University Hospitals, Nottingham NG51PB, UK., Abdel-Fatah TM; Department of Oncology, Nottingham University Hospitals, Nottingham NG51PB, UK., Agarwal D; School of Science and Technology, Nottingham Trent University, Clifton campus, Nottingham NG11 8NS, UK., Doherty R; Academic Unit of Oncology, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Nottingham NG51PB, UK., Croteau DL; Laboratory of Molecular Gerontology, Biomedical Research Center, National Institute on Aging, National Institutes of Health, Baltimore, MA 21224-6825, USA., Moseley PM; Department of Oncology, Nottingham University Hospitals, Nottingham NG51PB, UK., Hameed K; Department of Oncology, Nottingham University Hospitals, Nottingham NG51PB, UK., Green A; Department of Pathology, School of Medicine, University of Nottingham, Nottingham NG51PB, UK and., Aleskandarany MA; Department of Pathology, School of Medicine, University of Nottingham, Nottingham NG51PB, UK and., Rakha EA; Department of Pathology, School of Medicine, University of Nottingham, Nottingham NG51PB, UK and., Patterson K; Academic Unit of Molecular Oncology, Department of Oncology, Medical School Sheffield Cancer Research Centre, University of Sheffield, Sheffield S10 2RX, UK., Ball G; School of Science and Technology, Nottingham Trent University, Clifton campus, Nottingham NG11 8NS, UK., Chan SY; Department of Oncology, Nottingham University Hospitals, Nottingham NG51PB, UK., Ellis IO; Laboratory of Molecular Gerontology, Biomedical Research Center, National Institute on Aging, National Institutes of Health, Baltimore, MA 21224-6825, USA., Bohr VA; Laboratory of Molecular Gerontology, Biomedical Research Center, National Institute on Aging, National Institutes of Health, Baltimore, MA 21224-6825, USA., Bryant HE; Academic Unit of Molecular Oncology, Department of Oncology, Medical School Sheffield Cancer Research Centre, University of Sheffield, Sheffield S10 2RX, UK., Madhusudan S; Academic Unit of Oncology, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Nottingham NG51PB, UK, Department of Oncology, Nottingham University Hospitals, Nottingham NG51PB, UK, srinivasan.madhusudan@nottingham.ac.uk.
Jazyk:	angličtina
Zdroj:	Carcinogenesis [Carcinogenesis] 2016 Jan; Vol. 37 (1), pp. 63-71. Date of Electronic Publication: 2015 Nov 19.
DOI:	10.1093/carcin/bgv163
Abstrakt:	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. (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
Databáze:	MEDLINE
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