2026-06-10T22:12:02Zhttps://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 b2ce4fa6-6c6b-4df9-8ce7-983022a804ea 600 Bullock, Esme 2228986e-43b2-481d-a830-ff29b5ad2948 600 Xiao, Xue 73cf1739-b30c-435c-a656-4179086c9816 600 Guo, Jingjing fc86d8aa-f841-45c4-a1c3-563b9f1a1673 600 Zhu, Xuan 69026810-e25f-4a85-ba83-6fa040070c4d 600 Gómez Cuadrado, Laura 928 600 0000-0002-4754-2582 Oxvig, Claus d16b5e27-5762-4b91-9c63-b0fdb96401ef 600 Mallon, Elizabeth 615c90eb-6465-4156-a0d7-15be20294e85 600 Ammar, Aula 337e76c5-fb7f-43b0-a88e-c3181d38b5e5 600 Malty, Amna 9a8718c4-5242-4edc-8f9e-ad8ae9ff81cc 600 Pennel, Kathryn 1cb9278c-dd55-40db-8cf5-8cf473163f45 600 Edwards, Joanne beee3386-4db9-42a2-9977-88ad9413acbe 600 Brunton, Valerie G. 647cce9b-b9ca-4776-9053-5bfb5be6858d 600 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 THUMBNAIL Mabruk-CM_2026.pdf.jpg Mabruk-CM_2026.pdf.jpg IM Thumbnail image/jpeg 4782 https://riubu.ubu.es/bitstream/10259/11821/4/Mabruk-CM_2026.pdf.jpg 13228094f127c2a5913f2a7b64436943 MD5 4 LICENSE license.txt license.txt text/plain; charset=utf-8 1362 https://riubu.ubu.es/bitstream/10259/11821/3/license.txt 5d013bfa6e473ff0db22cd82a4d71a70 MD5 3 CC-LICENSE license_rdf license_rdf application/rdf+xml; charset=utf-8 908 https://riubu.ubu.es/bitstream/10259/11821/2/license_rdf 0175ea4a2d4caec4bbcc37e300941108 MD5 2 ORIGINAL Mabruk-CM_2026.pdf Mabruk-CM_2026.pdf application/pdf 4182034 https://riubu.ubu.es/bitstream/10259/11821/1/Mabruk-CM_2026.pdf 6fe5a641571bcf63e0fcf344dd6e2765 MD5 1 10259/11821 oai:riubu.ubu.es:10259/11821 2026-06-09 08:24:29.432 Repositorio Institucional de la Universidad de Burgos bubrep@ubu.es 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