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Title: Evaluating the prognostic and predictive potential of FKBPL and associated proteins as biomarkers in breast and ovarian cancer
Author: Nelson, Laura
ISNI:       0000 0004 5369 7219
Awarding Body: Queen's University Belfast
Current Institution: Queen's University Belfast
Date of Award: 2015
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Despite adjuvant systemic therapies improving breast cancer survival rates, some patients are over- or under-treated. This is particularly problematic for the management of early stage ER+/LN- breast cancers. Identifying patients at a higher risk of relapse for whom additional adjuvant chemotherapy is necessary, remains a significant challenge. The primary focus of this thesis was to evaluate the prognostic potential of FKBPL within breast TMA cohorts, and as part of a meta-analysis. FKBPL was shown to be an independent prognostic marker, which is able to predict breast cancer specific survival in ER positive, node positive patients. I As many prognostic tests now focus on the inclusion of multiple markers, the prognostic ability of two FKBPL-associated proteins, phospho-ERα and p21, were also assessed, however both failed to correlate with survival. In an attempt to evaluate the prognostic potential of additional FKBPL-associated proteins, the relationship between FKBPL and an FKBPL-interacting protein, USP19, was characterised in breast cancer cell lines. After an interaction between the two proteins was confirmed, subsequent analysis identified a role for USP19 in the deubiquitination and stabilisation of FKBPL. USP19 was shown to positively regulate FKBPL protein expression in breast cancer cell lines, functionally suppressing breast cancer cell proliferation . . ALM201, an anti-angiogenic peptide based on FKBPLs active anti-angiogenic domain, is soon to enter Phase 1111 clinical trials in ovarian cancer patients. Therefore, the current study also aimed to evaluate FKBPL's prognostic potential within an ovarian cancer TMA cohort, with the potential to utilize the FKBPL biomarker as a companion diagnostic. Unfortunately, FKBPL was not prognostic in the ovarian cancer setting. In conclusion, FKBPL has the ability to further stratify ER+/LN- breast cancer patients, identifying patients who may benefit from additional adjuvant chemotherapy. Validating the prognostic potential of USP19, within the breast cancer setting might prove beneficial to further sensitise the marker.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available