FKBPL: a marker of good prognosis in breast cancer
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Laura Nelson1,*, Hayley D. McKeen1,*, Andrea Marshall2,*, Laoighse Mulrane3, Jane Starczynski4, Sarah J. Storr5, Fiona Lanigan3, Christopher Byrne6, Ken Arthur7, Shauna Hegarty8, Ahlam Abdunnabi Ali1, Fiona Furlong1, Helen O. McCarthy1, Ian O. Ellis5, Andrew R. Green5, Emad Rakha5, Leonie Young6, Ian Kunkler10, Jeremy Thomas10, Wilma Jack10, David Cameron10, Karin Jirström11, Anita Yakkundi1, Lana McClements1, Stewart G. Martin5, William M. Gallagher3, Janet Dunn2, John Bartlett4,9, Darran O’Connor3, Tracy Robson1
1School of Pharmacy, Queen's University Belfast, Belfast, United Kingdom
2Warwick Clinical Trials Unit, University of Warwick, Coventry, United Kingdom
3Conway Institute, University College Dublin, Dublin, Ireland
4Ontario Institute for Cancer Research, Toronto, Canada
5Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Nottingham, United Kingdom
6Royal College of Surgeons Ireland, Dublin, Ireland
7Northern Ireland Molecular Pathology Laboratory, CCRCB, Queens University Belfast, Belfast, United Kingdom
8Department of Pathology, Royal Group of Hospitals, Grosvenor Road, Belfast, United Kingdom
9Edinburgh Cancer Research Centre, The University of Edinburgh, Edinburgh, United Kingdom
10Edinburgh Breast Unit, The University of Edinburgh, Edinburgh, United Kingdom
11Department of Clinical Sciences, Lund University, Sweden
*These authors have contributed equally to this work
Tracy Robson, e-mail: firstname.lastname@example.org
Keywords: FKBPL, breast cancer, biomarker, personalized medicine
Received: January 27, 2015 Accepted: March 09, 2015 Published: April 03, 2015
FK506-binding protein-like (FKBPL) has established roles as an anti-tumor protein, with a therapeutic peptide based on this protein, ALM201, shortly entering phase I/II clinical trials. Here, we evaluated FKBPL’s prognostic ability in primary breast cancer tissue, represented on tissue microarrays (TMA) from 3277 women recruited into five independent retrospective studies, using immunohistochemistry (IHC). In a meta-analysis, FKBPL levels were a significant predictor of BCSS; low FKBPL levels indicated poorer breast cancer specific survival (BCSS) (hazard ratio (HR) = 1.30, 95% confidence interval (CI) 1.14–1.49, p < 0.001). The prognostic impact of FKBPL remained significant after adjusting for other known prognostic factors (HR = 1.25, 95% CI 1.07–1.45, p = 0.004). For the sub-groups of 2365 estrogen receptor (ER) positive patients and 1649 tamoxifen treated patients, FKBPL was significantly associated with BCSS (HR = 1.34, 95% CI 1.13–1.58, p < 0.001, and HR = 1.25, 95% CI 1.04–1.49, p = 0.02, respectively). A univariate analysis revealed that FKBPL was also a significant predictor of relapse free interval (RFI) within the ER positive patient group, but it was only borderline significant within the smaller tamoxifen treated patient group (HR = 1.32 95% CI 1.05–1.65, p = 0.02 and HR = 1.23 95% CI 0.99–1.54, p = 0.06, respectively). The data suggests a role for FKBPL as a prognostic factor for BCSS, with the potential to be routinely evaluated within the clinic.
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