2026-06-10T20:46:27Zhttps://riubu.ubu.es/oai/request

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

Mabruk, Zeanap Bullock, Esme Xiao, Xue Guo, Jingjing Zhu, Xuan Gómez Cuadrado, Laura Oxvig, Claus Mallon, Elizabeth Ammar, Aula Malty, Amna Pennel, Kathryn Edwards, Joanne 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 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) application/pdf eng Wiley Cancer Medicine. V. 15, n. 4, art. e71815 https://doi.org/10.1002/cam4.71815 Atribución 4.0 Internacional http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess Breast cancer IGF-1 signalling Invasive lobular carcinoma Pregnancy-associated plasma protein-A Mamas-Cáncer Breast-Cancer High Expression of PAPP‐A Predicts Poor Outcomes in Oestrogen Receptor‐Positive Breast Cancer Patients info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Cancer Medicine 15 4 e71815