{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T16:49:06Z","timestamp":1761324546362,"version":"build-2065373602"},"reference-count":52,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T00:00:00Z","timestamp":1695859200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"School of Medicine, Collegium Medicum, University of Warmia and Mazury","award":["61.610.001-110"],"award-info":[{"award-number":["61.610.001-110"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: The inappropriate action of WNT4 and estrogens affects uterine homeostasis and function, and may lead to endometrial cancer (EC). Objective: The aim was to evaluate the alterations of WNT4 gene expression and WNT4 protein immunoreactivity (Ir) in EC, considering tumor characteristics, the clinicopathological association and estrogen dependence. Methods: WNT4 mRNA levels were compared between benign (control) endometrium (n = 8) and endometroid EC (EEC) and non-endometroid EC (non-EEC) samples (n = 28) using the real-time PCR technique. The WNT4-Ir and ER\u03b1-Ir were evaluated by immunohistochemistry (IHC). WNT4 mRNA gene and WNT4-Ir were correlated with clinicopathological and blood morphological parameters. Overall survival (OS) was assessed. The bioanalysis was utilized to study WNT4 expression in large patient cohort (n = 549). Results: WNT4 gene expression was decreased in EC samples (specifically in EEC but not in non-EEC) compared to the control. The WNT4 gene expression was also decreased in EC samples categorized by the tumor characteristics. There was no statistical difference in WNT4-Ir or ER\u03b1-Ir between the control and EC. There was no correlation between OS and WNT4 gene expression and WNT4-Ir. Bioanalysis showed that WNT4 and ESR1 gene expression alterations tended to be mutually exclusive. An alteration in WNT4 expression was found in different histological tumor types in a large group of EC patients. Conclusions: There is a great need to evaluate the molecular background of EC. Our study suggests that the WNT4 gene has the potential to be a marker of functional estrogen signaling in EEC.<\/jats:p>","DOI":"10.3390\/cancers15194780","type":"journal-article","created":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T05:48:13Z","timestamp":1695966493000},"page":"4780","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["WNT4 Gene and Protein Expression in Endometrial Cancer and Its Significance"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2738-8952","authenticated-orcid":false,"given":"Jolanta","family":"Kiewisz","sequence":"first","affiliation":[{"name":"Department of Human Histology and Embryology, School of Medicine, Collegium Medicum, University of Warmia and Mazury, 10-082 Olsztyn, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomasz","family":"Wa\u015bniewski","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, School of Medicine, Collegium Medicum, University of Warmia and Mazury, 10-082 Olsztyn, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacek","family":"Kie\u017cun","sequence":"additional","affiliation":[{"name":"Department of Human Histology and Embryology, School of Medicine, Collegium Medicum, University of Warmia and Mazury, 10-082 Olsztyn, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2274-8867","authenticated-orcid":false,"given":"Agnieszka","family":"Skowro\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Human Physiology, School of Medicine, Collegium Medicum, University of Warmia and Mazury, 10-082 Olsztyn, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8213-4381","authenticated-orcid":false,"given":"Monika M.","family":"Kaczmarek","sequence":"additional","affiliation":[{"name":"Department of Hormonal Action Mechanisms, Institute of Animal Reproduction and Food Research, Polish Academy of Science, 10-748 Olsztyn, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B\u0142a\u017cej","family":"Sz\u00f3stak","sequence":"additional","affiliation":[{"name":"Department of Pathomorphology, The Regional Specialist Hospital, 10-561 Olsztyn, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna E.","family":"Kowalczyk","sequence":"additional","affiliation":[{"name":"Department of Human Histology and Embryology, School of Medicine, Collegium Medicum, University of Warmia and Mazury, 10-082 Olsztyn, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9801-8166","authenticated-orcid":false,"given":"Zbigniew","family":"Kmie\u0107","sequence":"additional","affiliation":[{"name":"Department of Human Histology and Embryology, School of Medicine, Collegium Medicum, University of Warmia and Mazury, 10-082 Olsztyn, Poland"},{"name":"Department of Histology, Medical University of Gdansk, 80-211 Gdansk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,28]]},"reference":[{"key":"ref_1","first-page":"1531","article-title":"Obesity, Endogenous Hormones, and Endometrial Cancer Risk: A Synthetic Review","volume":"11","author":"Kaaks","year":"2002","journal-title":"Cancer Epidemiol. 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