title: FKBPL: a marker of good prognosis in breast cancer.
abstract: 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.
authors.affiliation: School of Pharmacy, Queen's University Belfast, Belfast, United Kingdom.
authors.forename: Laura
authors.initials: L
authors.lastname: Nelson
authors.affiliation: School of Pharmacy, Queen's University Belfast, Belfast, United Kingdom.
authors.forename: Hayley D
authors.initials: HD
authors.lastname: McKeen
authors.affiliation: Warwick Clinical Trials Unit, University of Warwick, Coventry, United Kingdom.
authors.forename: Andrea
authors.initials: A
authors.lastname: Marshall
authors.affiliation: Conway Institute, University College Dublin, Dublin, Ireland.
authors.forename: Laoighse
authors.initials: L
authors.lastname: Mulrane
authors.affiliation: Ontario Institute for Cancer Research, Toronto, Canada.
authors.forename: Jane
authors.initials: J
authors.lastname: Starczynski
authors.affiliation: Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Storr
authors.affiliation: Conway Institute, University College Dublin, Dublin, Ireland.
authors.forename: Fiona
authors.initials: F
authors.lastname: Lanigan
authors.affiliation: Royal College of Surgeons Ireland, Dublin, Ireland.
authors.forename: Christopher
authors.initials: C
authors.lastname: Byrne
authors.affiliation: Northern Ireland Molecular Pathology Laboratory, CCRCB, Queens University Belfast, Belfast, United Kingdom.
authors.forename: Ken
authors.initials: K
authors.lastname: Arthur
authors.affiliation: Department of Pathology, Royal Group of Hospitals, Grosvenor Road, Belfast, United Kingdom.
authors.forename: Shauna
authors.initials: S
authors.lastname: Hegarty
authors.affiliation: School of Pharmacy, Queen's University Belfast, Belfast, United Kingdom.
authors.forename: Ahlam Abdunnabi
authors.initials: AA
authors.lastname: Ali
authors.affiliation: School of Pharmacy, Queen's University Belfast, Belfast, United Kingdom.
authors.forename: Fiona
authors.initials: F
authors.lastname: Furlong
authors.affiliation: School of Pharmacy, Queen's University Belfast, Belfast, United Kingdom.
authors.forename: Helen O
authors.initials: HO
authors.lastname: McCarthy
authors.affiliation: Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Ian O
authors.initials: IO
authors.lastname: Ellis
authors.affiliation: Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Green
authors.affiliation: Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Emad
authors.initials: E
authors.lastname: Rakha
authors.affiliation: Royal College of Surgeons Ireland, Dublin, Ireland.
authors.forename: Leonie
authors.initials: L
authors.lastname: Young
authors.affiliation: Edinburgh Breast Unit, The University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Ian
authors.initials: I
authors.lastname: Kunkler
authors.affiliation: Edinburgh Breast Unit, The University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Thomas
authors.affiliation: Edinburgh Breast Unit, The University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Wilma
authors.initials: W
authors.lastname: Jack
authors.affiliation: Edinburgh Breast Unit, The University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Cameron
authors.affiliation: Department of Clinical Sciences, Lund University, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Jirström
authors.affiliation: School of Pharmacy, Queen's University Belfast, Belfast, United Kingdom.
authors.forename: Anita
authors.initials: A
authors.lastname: Yakkundi
authors.affiliation: School of Pharmacy, Queen's University Belfast, Belfast, United Kingdom.
authors.forename: Lana
authors.initials: L
authors.lastname: McClements
authors.affiliation: Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Stewart G
authors.initials: SG
authors.lastname: Martin
authors.affiliation: Conway Institute, University College Dublin, Dublin, Ireland.
authors.forename: William M
authors.initials: WM
authors.lastname: Gallagher
authors.affiliation: Warwick Clinical Trials Unit, University of Warwick, Coventry, United Kingdom.
authors.forename: Janet
authors.initials: J
authors.lastname: Dunn
authors.affiliation: Ontario Institute for Cancer Research, Toronto, Canada.|Edinburgh Cancer Research Centre, The University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: John
authors.initials: J
authors.lastname: Bartlett
authors.affiliation: Conway Institute, University College Dublin, Dublin, Ireland.
authors.forename: Darran
authors.initials: D
authors.lastname: O'Connor
authors.affiliation: School of Pharmacy, Queen's University Belfast, Belfast, United Kingdom.
authors.forename: Tracy
authors.initials: T
authors.lastname: Robson
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D020104:Immunophilins / Q000235:genetics* / Q000378:metabolism*; D057285:Precision Medicine; D011379:Prognosis; D016019:Survival Analysis; D022021:Tacrolimus Binding Proteins
chemical_list: C400101:FKBPL protein, human; D022021:Tacrolimus Binding Proteins; D020104:Immunophilins
keywords: FKBPL; biomarker; breast cancer; personalized medicine