FKBPL: A marker of good prognosis in breast cancer

Nelson, L; McKeen, HD; Marshall, A; Mulrane, L; Starczynski, J; Storr, SJ; Lanigan, F; Byrne, C; Arthur, K; Hegarty, S; Ali, AA; Furlong, F; McCarthy, HO; Ellis, IO; Green, AR; Rakha, E; Young, L; Kunkler, I; Thomas, J; Jack, W; Cameron, D; Jirström, K; Yakkundi, A; McClements, L; Martin, SG; Gallagher, WM; Dunn, J; Bartlett, J; O'Connor, D; Robson, T

FKBPL: A marker of good prognosis in breast cancer

Nelson, L McKeen, HD Marshall, A Mulrane, L Starczynski, J Storr, SJ Lanigan, F Byrne, C Arthur, K Hegarty, S Ali, AA Furlong, F McCarthy, HO Ellis, IO Green, AR Rakha, E Young, L Kunkler, I Thomas, J Jack, W Cameron, D Jirström, K Yakkundi, A McClements, L

Martin, SG Gallagher, WM Dunn, J Bartlett, J O'Connor, D Robson, T

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Publication Type:: Journal Article
Citation:: Oncotarget, 2015, 6 (14), pp. 12209 - 12223
Issue Date:: 2015-01-01

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Field	Value	Language
dc.contributor.author	Nelson, L	en_US
dc.contributor.author	McKeen, HD	en_US
dc.contributor.author	Marshall, A	en_US
dc.contributor.author	Mulrane, L	en_US
dc.contributor.author	Starczynski, J	en_US
dc.contributor.author	Storr, SJ	en_US
dc.contributor.author	Lanigan, F	en_US
dc.contributor.author	Byrne, C	en_US
dc.contributor.author	Arthur, K	en_US
dc.contributor.author	Hegarty, S	en_US
dc.contributor.author	Ali, AA	en_US
dc.contributor.author	Furlong, F	en_US
dc.contributor.author	McCarthy, HO	en_US
dc.contributor.author	Ellis, IO	en_US
dc.contributor.author	Green, AR	en_US
dc.contributor.author	Rakha, E	en_US
dc.contributor.author	Young, L	en_US
dc.contributor.author	Kunkler, I	en_US
dc.contributor.author	Thomas, J	en_US
dc.contributor.author	Jack, W	en_US
dc.contributor.author	Cameron, D	en_US
dc.contributor.author	Jirström, K	en_US
dc.contributor.author	Yakkundi, A	en_US
dc.contributor.author	McClements, L https://orcid.org/0000-0002-4911-1014	en_US
dc.contributor.author	Martin, SG	en_US
dc.contributor.author	Gallagher, WM	en_US
dc.contributor.author	Dunn, J	en_US
dc.contributor.author	Bartlett, J	en_US
dc.contributor.author	O'Connor, D	en_US
dc.contributor.author	Robson, T	en_US
dc.date.available	2015-03-09	en_US
dc.date.issued	2015-01-01	en_US
dc.identifier.citation	Oncotarget, 2015, 6 (14), pp. 12209 - 12223	en_US
dc.identifier.uri	http://hdl.handle.net/10453/127448
dc.description.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.	en_US
dc.relation.ispartof	Oncotarget	en_US
dc.relation.isbasedon	10.18632/oncotarget.3528	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Breast Neoplasms	en_US
dc.subject.mesh	Immunophilins	en_US
dc.subject.mesh	Prognosis	en_US
dc.subject.mesh	Survival Analysis	en_US
dc.subject.mesh	Cohort Studies	en_US
dc.subject.mesh	Female	en_US
dc.subject.mesh	Precision Medicine	en_US
dc.title	FKBPL: A marker of good prognosis in breast cancer	en_US
dc.type	Journal Article
utslib.citation.volume	14	en_US
utslib.citation.volume	6	en_US
utslib.for	1112 Oncology and Carcinogenesis	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	open_access
pubs.issue	14	en_US
pubs.publication-status	Published	en_US
pubs.volume	6	en_US

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.

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http://hdl.handle.net/10453/127448