FKBPL: a marker of good prognosis in breast cancer

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

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.

Citation

Nelson, L., McKeen, H. D., Ellis, I., Rakha, E., Marshall, A., Mulrane, L., Starczynski, J., Storr, S. J., Lanigan, F., Byrne, C., Arthur, K., Hegarty, S., Abdunnabi Ali, A., Furlong, F., McCarthy, H. O., Ellis, I. O., Green, A. R., Rakha, E., Young, L., Kunkler, I., …Robson, T. (2015). FKBPL: a marker of good prognosis in breast cancer. Oncotarget, 6(14), 12209-12223. https://doi.org/10.18632/oncotarget.3528

• Journal Article Type: Article
• Acceptance Date: Mar 9, 2015
• Online Publication Date: Apr 3, 2015
• Publication Date: Apr 3, 2015
• Deposit Date: Aug 14, 2018
• Publicly Available Date: Oct 17, 2018
• Electronic ISSN: 1949-2553
• Publisher: Impact Journals
• Peer Reviewed: Peer Reviewed
• Volume: 6
• Issue: 14
• Pages: 12209-12223
• DOI: https://doi.org/10.18632/oncotarget.3528
• Keywords: FKBPL, breast cancer, biomarker, personalized medicine
• Public URL: https://nottingham-repository.worktribe.com/output/1107030
• Publisher URL: http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=3528&path[]=9217
• PMID: 00035900
• Contract Date: Oct 17, 2018