RT info:eu-repo/semantics/article
T1 High Expression of PAPP‐A Predicts Poor Outcomes in Oestrogen Receptor‐Positive Breast Cancer Patients
A1 Mabruk, Zeanap
A1 Bullock, Esme
A1 Xiao, Xue
A1 Guo, Jingjing
A1 Zhu, Xuan
A1 Gómez Cuadrado, Laura
A1 Oxvig, Claus
A1 Mallon, Elizabeth
A1 Ammar, Aula
A1 Malty, Amna
A1 Pennel, Kathryn
A1 Edwards, Joanne
A1 Brunton, Valerie G.
K1 Breast cancer
K1 IGF-1 signalling
K1 Invasive lobular carcinoma
K1 Pregnancy-associated plasma protein-A
K1 Mamas-Cáncer
K1 Breast-Cancer
AB Introduction: Insulin-like growth factor 1 (IGF-1)/IGF-1 receptor (IGF-1R) signalling is activated in breast cancer and asso-ciated with disease progression. Pregnancy-associated plasma protein-A (PAPP-A) is a metalloproteinase that can cleave IGFbinding proteins leading to the release of bioactive IGF-1 and the subsequent activation of IGF-1 signalling. Here, we aimed toassess the prognostic significance of PAPP-A in breast cancer.Methods: Breast cancer tissue microarrays were stained for PAPP-A and expression correlated with survival and other clinicalfeatures. Analysis of publicly available data sets was carried out to determine associations between PAPPA and gene sets associ-ated with IGF-1/IGF-1R pathway activation.Results: PAPP-A was expressed in both the tumour and stromal compartments in breast cancer specimens and was higher inoestrogen receptor (ER)-negative (ER-) than ER-positive (ER+) cases. There was a significant association between high PAPP-Aexpression and reduced cancer-specific survival (CSS) in ER+ (HR 1.389, 95% CI 1.051–1.836, p = 0.021) but not ER- patients (HR1.040, 95% CI 0.712–1.598, p = 0.838). In a second cohort of ER+ invasive lobular carcinoma (ILC) PAPP-A expression was alsoassociated with reduced CSS (HR 1.765, 95% CI 1.098–2.836, p = 0.019). PAPPA correlated with REACTOME PI3K-AKT andIGF1R signalling gene sets in ER+ breast cancers.Conclusion: High expression of PAPP-A is associated with poor prognosis in ER+ breast cancer and correlates with IGF-1/IGF-1R pathway activation
PB Wiley
SN 2045-7634
YR 2026
FD 2026-04
LK https://hdl.handle.net/10259/11821
UL https://hdl.handle.net/10259/11821
LA eng
NO This work was funded by an Endeavour Scholarship (734/2018/878) to Z.M.; Cancer Research UK (C157/A23219) to L.G.-C. and (CANTAC721\100018) to E.B.; Sichuan Science and Technology Program (NO. 2022YFS0601) and Sichuan Provincial People's Hospital (NO. 2021ZX02) to X.X. and was supported by the Cancer Research UK Scotland Centre (CTRQQR-2021\100006)
DS Repositorio Institucional de la Universidad de Burgos
RD 10-jun-2026