2026-06-10T20:46:20Zhttps://riubu.ubu.es/oai/request

oai:riubu.ubu.es:10259/118212026-06-09T06:24:29Zcom_10259_6168com_10259_5086com_10259_2604col_10259_6169

00925njm 22002777a 4500 dc 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. author 2026-04 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 2045-7634 https://hdl.handle.net/10259/11821 10.1002/cam4.71815 2045-7634 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