{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T19:46:39Z","timestamp":1787168799043,"version":"build-2736575974"},"reference-count":41,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T00:00:00Z","timestamp":1776038400000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C157\/A23219"],"award-info":[{"award-number":["C157\/A23219"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["CANTAC721\\100018"],"award-info":[{"award-number":["CANTAC721\\100018"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["CTRQQR\u20102021\\100006"],"award-info":[{"award-number":["CTRQQR\u20102021\\100006"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012542","name":"Sichuan Provincial Science and Technology Support Program","doi-asserted-by":"publisher","award":["NO.2022YFS0601"],"award-info":[{"award-number":["NO.2022YFS0601"]}],"id":[{"id":"10.13039\/100012542","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Insulin\u2010like growth factor 1 (IGF\u20101)\/IGF\u20101 receptor (IGF\u20101R) signalling is activated in breast cancer and associated with disease progression. Pregnancy\u2010associated plasma protein\u2010A (PAPP\u2010A) is a metalloproteinase that can cleave IGF binding proteins leading to the release of bioactive IGF\u20101 and the subsequent activation of IGF\u20101 signalling. Here, we aimed to assess the prognostic significance of PAPP\u2010A in breast cancer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Breast cancer tissue microarrays were stained for PAPP\u2010A and expression correlated with survival and other clinical features. Analysis of publicly available data sets was carried out to determine associations between\n                      <jats:italic>PAPPA<\/jats:italic>\n                      and gene sets associated with IGF\u20101\/IGF\u20101R pathway activation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      PAPP\u2010A was expressed in both the tumour and stromal compartments in breast cancer specimens and was higher in oestrogen receptor (ER)\u2010negative (ER\u2010) than ER\u2010positive (ER+) cases. There was a significant association between high PAPP\u2010A expression and reduced cancer\u2010specific survival (CSS) in ER+ (HR 1.389, 95% CI 1.051\u20131.836,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.021) but not ER\u2010 patients (HR 1.040, 95% CI 0.712\u20131.598,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.838). In a second cohort of ER+ invasive lobular carcinoma (ILC) PAPP\u2010A expression was also associated with reduced CSS (HR 1.765, 95% CI 1.098\u20132.836,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.019).\n                      <jats:italic>PAPPA<\/jats:italic>\n                      correlated with REACTOME PI3K\u2010AKT and IGF1R signalling gene sets in ER+ breast cancers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>High expression of PAPP\u2010A is associated with poor prognosis in ER+ breast cancer and correlates with IGF\u20101\/IGF\u20101R pathway activation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.71815","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T11:31:00Z","timestamp":1776079860000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["High Expression of\n                    <scp>PAPP<\/scp>\n                    \u2010A Predicts Poor Outcomes in Oestrogen Receptor\u2010Positive Breast Cancer Patients"],"prefix":"10.1002","volume":"15","author":[{"given":"Zeanap","family":"Mabruk","sequence":"first","affiliation":[{"name":"Cancer Research UK Scotland Centre (Edinburgh), Institute of Genetics &amp; Cancer University of Edinburgh  Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esme","family":"Bullock","sequence":"additional","affiliation":[{"name":"Cancer Research UK Scotland Centre (Edinburgh), Institute of Genetics &amp; Cancer University of Edinburgh  Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8824-2439","authenticated-orcid":false,"given":"Xue","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Pathology, Sichuan Provincial People's Hospital, School of Medicine University of Electronic Science and Technology of China  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Pathology, Sichuan Provincial People's Hospital, School of Medicine University of Electronic Science and Technology of China  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Sichuan Provincial People's Hospital, School of Medicine University of Electronic Science and Technology of China  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"G\u00f3mez\u2010Cuadrado","sequence":"additional","affiliation":[{"name":"Cancer Research UK Scotland Centre (Edinburgh), Institute of Genetics &amp; Cancer University of Edinburgh  Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claus","family":"Oxvig","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics University of Aarhus  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Mallon","sequence":"additional","affiliation":[{"name":"Department of Pathology Queen Elizabeth University Hospital  Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0375-062X","authenticated-orcid":false,"given":"Aula","family":"Ammar","sequence":"additional","affiliation":[{"name":"School of Cancer Sciences, Wolfson Wohl Cancer Research Centre University of Glasgow  Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amna","family":"Malty","sequence":"additional","affiliation":[{"name":"School of Cancer Sciences, Wolfson Wohl Cancer Research Centre University of Glasgow  Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0186-1331","authenticated-orcid":false,"given":"Kathryn","family":"Pennel","sequence":"additional","affiliation":[{"name":"School of Cancer Sciences, Wolfson Wohl Cancer Research Centre University of Glasgow  Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7192-6906","authenticated-orcid":false,"given":"Joanne","family":"Edwards","sequence":"additional","affiliation":[{"name":"School of Cancer Sciences, Wolfson Wohl Cancer Research Centre University of Glasgow  Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7778-8794","authenticated-orcid":false,"given":"Valerie G.","family":"Brunton","sequence":"additional","affiliation":[{"name":"Cancer Research UK Scotland Centre (Edinburgh), Institute of Genetics &amp; 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