{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:31:53Z","timestamp":1791930713506,"version":"4.3.4"},"reference-count":60,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T00:00:00Z","timestamp":1707264000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Arvid Nilssons Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pregnancy-associated plasma protein-A (PAPP-A) and PAPP-A2 modulate insulin-like growth factor (IGF) action and are inhibited by the stanniocalcins (STC1 and STC2). We previously demonstrated increased PAPP-A and IGF activity in ascites from women with ovarian carcinomas. In this prospective, longitudinal study of 107 women with ovarian cancer and ascites accumulation, we determined corresponding serum and ascites levels of IGF-1, IGF-2, PAPP-A, PAPP-A2, STC1, and STC2 and assessed their relationship with mortality. As compared to serum, we found highly increased ascites levels of PAPP-A (51-fold) and PAPP-A2 (4-fold). Elevated levels were also observed for IGF-1 (12%), STC1 (90%) and STC2 (68%). In contrast, IGF-2 was reduced by 29% in ascites. Patients were followed for a median of 38.4 months (range: 45 days to 8.9 years), during which 73 patients (68.2%) died. Overall survival was longer for patients with high serum IGF-1 (hazard ratio (HR) per doubling in protein concentration: 0.60, 95% CI: 0.40\u20130.90). However, patients with high ascites levels of IGF-1 showed a poorer prognosis (HR: 2.00 (1.26\u20133.27)). High serum and ascites IGF-2 levels were associated with increased risk of mortality (HR: 2.01 (1.22\u20133.30) and HR: 1.78 (1.24\u20132.54), respectively). Similarly, serum PAPP-A2 was associated with mortality (HR: 1.26 (1.08\u20131.48)). Our findings demonstrate the presence and activity of the IGF system in the local tumor ecosystem, which is likely a characteristic feature of malignant disease and plays a role in its peritoneal dissemination. The potential clinical implications are supported by our finding that serum levels of the proteins are associated with patient prognosis.<\/jats:p>","DOI":"10.3390\/ijms25042014","type":"journal-article","created":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T06:12:58Z","timestamp":1707286378000},"page":"2014","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The IGF\u2013PAPP-A\u2013Stanniocalcin Axis in Serum and Ascites Associates with Prognosis in Patients with Ovarian Cancer"],"prefix":"10.3390","volume":"25","author":[{"given":"Rikke","family":"Hjortebjerg","sequence":"first","affiliation":[{"name":"Steno Diabetes Center Odense, Odense University Hospital, 5000 Odense, Denmark"},{"name":"Department of Clinical Research, University of Southern Denmark, 5230 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claus","family":"H\u00f8gdall","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Juliane Marie Center, Rigshospitalet, 2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristian Horsman","family":"Hansen","sequence":"additional","affiliation":[{"name":"Endocrine Research Unit, Department of Endocrinology, Odense University Hospital, 5000 Odense, Denmark"},{"name":"OPEN Lab, Odense University Hospital, 5000 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4689-5658","authenticated-orcid":false,"given":"Estrid","family":"H\u00f8gdall","sequence":"additional","affiliation":[{"name":"Department of Pathology, Herlev University Hospital, 2730 Herlev, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Frystyk","sequence":"additional","affiliation":[{"name":"Department of Clinical Research, University of Southern Denmark, 5230 Odense, Denmark"},{"name":"Endocrine Research Unit, Department of Endocrinology, Odense University Hospital, 5000 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"595","DOI":"10.3389\/fonc.2018.00595","article-title":"Ascites Volumes and the Ovarian Cancer Microenvironment","volume":"8","author":"Penet","year":"2018","journal-title":"Front. 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