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Meta-Analysis
. 2015 May 20;6(14):12209-23.
doi: 10.18632/oncotarget.3528.

FKBPL: a marker of good prognosis in breast cancer

Laura Nelson  1 , Hayley D McKeen  1 , Andrea Marshall  2 , Laoighse Mulrane  3 , Jane Starczynski  4 , Sarah J Storr  5 , Fiona Lanigan  3 , Christopher Byrne  6 , Ken Arthur  7 , Shauna Hegarty  8 , Ahlam Abdunnabi Ali  1 , Fiona Furlong  1 , Helen O McCarthy  1 , Ian O Ellis  5 , Andrew R Green  5 , Emad Rakha  5 , Leonie Young  6 , Ian Kunkler  9 , Jeremy Thomas  9 , Wilma Jack  9 , David Cameron  9 , Karin Jirström  10 , Anita Yakkundi  1 , Lana McClements  1 , Stewart G Martin  5 , William M Gallagher  3 , Janet Dunn  2 , John Bartlett  4   11 , Darran O'Connor  3 , Tracy Robson  1
Affiliations
Meta-Analysis

FKBPL: a marker of good prognosis in breast cancer

Laura Nelson et al. Oncotarget. .

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.

Keywords: FKBPL; biomarker; breast cancer; personalized medicine.

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Figures

Figure 1
Figure 1. Optimisation of FKBPL antibody for IHC
(A) Optimisation of the FKBPL anti-body for IHC staining. Specificity was verified via Western blotting, and optimized for IHC using cell pellet arrays of parental (MCF-7 and MDA-B-231) and FKBPL overexpressing (3.1D2, 3.1D9; derived from MCF-7 and A3; derived from MDA-231) cell lines or following siRNA-mediated knockdown of FKBPL in MCF-7 cells. (B) Various expression levels of FKBPL protein in invasive breast carcinoma. Images (x10) represent tumour sections with absent (0), low (1+), moderate (2+) and high (3+) immunohistochemical staining intensity for FKBPL.
Figure 2
Figure 2. FKBPL expression Kaplan-Meier estimates of breast cancer specific survival for FKBPL in (A) cohort I (n = 290) (B) cohort II (n = 1214) (C) cohort III (n = 492) (D) cohort IV (n = 104) and (E) cohort V (n = 1169)
FKBPL histoscore was categorised into high and low groups using a cut-point of 190.
Figure 3
Figure 3. Hazard ratio plot of breast cancer specific survival against FKBPL levels by cohort using a one stage random effects meta-analysis model (n = 3279)
Figure 4
Figure 4. Hazard ratio plot of breast cancer specific survival against FKBPL levels by cohort using a one stage random effects meta-analysis model in (A) tamoxifen treated patients (n = 1649) and (B) ER-positive patients (n = 2365)
Figure 5
Figure 5. Hazard ratio plot of relapse free interval against FKBPL levels by cohort using a one stage random effects meta-analysis model in (A) tamoxifen treated patients (n = 1649) and (B) ER-positive patients (n = 2365)
See this image and copyright information in PMC

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