2026-06-10T19:22:43Zhttps://riubu.ubu.es/oai/requestoai:riubu.ubu.es:10259/118212026-06-09T06:24:29Zcom_10259_6168com_10259_5086com_10259_2604col_10259_6169
Repositorio Institucional de la Universidad de Burgos
author
Mabruk, Zeanap
author
Bullock, Esme
author
Xiao, Xue
author
Guo, Jingjing
author
Zhu, Xuan
author
Gómez Cuadrado, Laura
author
Oxvig, Claus
author
Mallon, Elizabeth
author
Ammar, Aula
author
Malty, Amna
author
Pennel, Kathryn
author
Edwards, Joanne
author
Brunton, Valerie G.
2026-06-08T11:59:51Z
2026-06-08T11:59:51Z
2026-04
2045-7634
https://hdl.handle.net/10259/11821
10.1002/cam4.71815
2045-7634
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
eng
Atribución 4.0 Internacional
Breast cancer
IGF-1 signalling
Invasive lobular carcinoma
Pregnancy-associated plasma protein-A
High Expression of PAPP‐A Predicts Poor Outcomes in Oestrogen Receptor‐Positive Breast Cancer Patients
info:eu-repo/semantics/article
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Mabruk-CM_2026.pdf