FKBPL: a marker of good prognosis in breast cancer

Laura Nelson, Hayley D. McKeen, Andrea Marshall, Laoighse Mulrane, Jane Starczynski, Sarah J. Storr, Fiona Lanigan, Christopher Byrne, Ken Arthur, Shauna Hegarty, Ahlam Abdunnabi Ali, Fiona Furlong, Helen O. McCarthy, Ian O. Ellis, Andrew R. Green, Emad Rakha, Leonie Young, Ian Kunkler, Jeremy Thomas, Wilma JackDavid Cameron, Karin Jirström, Anita Yakkundi, Lana McClements, Stewart G. Martin, William M. Gallagher, Janet Dunn, John Bartlett, Darran O'Connor, Tracy Robson

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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.

Original languageEnglish
Pages (from-to)12209-12223
Number of pages15
JournalOncotarget
Volume6
Issue number14
Early online date03 Apr 2015
Publication statusPublished - 03 Apr 2015

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