2026-06-10T20:47:16Zhttps://riubu.ubu.es/oai/request

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

High Expression of PAPP‐A Predicts Poor Outcomes in Oestrogen Receptor‐Positive Breast Cancer Patients 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. Breast cancer IGF-1 signalling Invasive lobular carcinoma Pregnancy-associated plasma protein-A Mamas-Cáncer Breast-Cancer 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) 2026-06-08T11:59:51Z 2026-06-08T11:59:51Z 2026-04 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion 2045-7634 https://hdl.handle.net/10259/11821 10.1002/cam4.71815 2045-7634 eng 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 application/pdf Wiley https://riubu.ubu.es/bitstream/10259/11821/4/Mabruk-CM_2026.pdf.jpg Hispana TEXT http://creativecommons.org/licenses/by/4.0/ RIUBU. Repositorio Institucional de la Universidad de Burgos https://hdl.handle.net/10259/11821