<i>WNT4</i> Gene and Protein Expression in Endometrial Cancer and Its Significance

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 <i>WNT4</i> gene expression and WNT4 protein immunoreactivity (Ir) in EC, considering tumor...

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Main Authors: Jolanta Kiewisz, Tomasz Waśniewski, Jacek Kieżun, Agnieszka Skowrońska, Monika M. Kaczmarek, Błażej Szóstak, Anna E. Kowalczyk, Zbigniew Kmieć
Format: Article
Language:English
Published: MDPI AG 2023-09-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/15/19/4780
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author Jolanta Kiewisz
Tomasz Waśniewski
Jacek Kieżun
Agnieszka Skowrońska
Monika M. Kaczmarek
Błażej Szóstak
Anna E. Kowalczyk
Zbigniew Kmieć
author_facet Jolanta Kiewisz
Tomasz Waśniewski
Jacek Kieżun
Agnieszka Skowrońska
Monika M. Kaczmarek
Błażej Szóstak
Anna E. Kowalczyk
Zbigniew Kmieć
author_sort Jolanta Kiewisz
collection DOAJ
description 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 <i>WNT4</i> gene expression and WNT4 protein immunoreactivity (Ir) in EC, considering tumor characteristics, the clinicopathological association and estrogen dependence. Methods: <i>WNT4</i> mRNA levels were compared between benign (control) endometrium (<i>n</i> = 8) and endometroid EC (EEC) and non-endometroid EC (non-EEC) samples (<i>n</i> = 28) using the real-time PCR technique. The WNT4-Ir and ERα-Ir were evaluated by immunohistochemistry (IHC). <i>WNT4</i> 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 (<i>n</i> = 549). Results: <i>WNT4</i> gene expression was decreased in EC samples (specifically in EEC but not in non-EEC) compared to the control. The <i>WNT4</i> gene expression was also decreased in EC samples categorized by the tumor characteristics. There was no statistical difference in WNT4-Ir or ERα-Ir between the control and EC. There was no correlation between OS and <i>WNT4</i> gene expression and WNT4-Ir. Bioanalysis showed that <i>WNT4</i> and <i>ESR1</i> gene expression alterations tended to be mutually exclusive. An alteration in <i>WNT4</i> 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 <i>WNT4</i> gene has the potential to be a marker of functional estrogen signaling in EEC.
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spelling doaj.art-6694e0d9b74440a581379805dfb04f4f2023-11-19T14:10:27ZengMDPI AGCancers2072-66942023-09-011519478010.3390/cancers15194780<i>WNT4</i> Gene and Protein Expression in Endometrial Cancer and Its SignificanceJolanta Kiewisz0Tomasz Waśniewski1Jacek Kieżun2Agnieszka Skowrońska3Monika M. Kaczmarek4Błażej Szóstak5Anna E. Kowalczyk6Zbigniew Kmieć7Department of Human Histology and Embryology, School of Medicine, Collegium Medicum, University of Warmia and Mazury, 10-082 Olsztyn, PolandDepartment of Gynecology and Obstetrics, School of Medicine, Collegium Medicum, University of Warmia and Mazury, 10-082 Olsztyn, PolandDepartment of Human Histology and Embryology, School of Medicine, Collegium Medicum, University of Warmia and Mazury, 10-082 Olsztyn, PolandDepartment of Human Physiology, School of Medicine, Collegium Medicum, University of Warmia and Mazury, 10-082 Olsztyn, PolandDepartment of Hormonal Action Mechanisms, Institute of Animal Reproduction and Food Research, Polish Academy of Science, 10-748 Olsztyn, PolandDepartment of Pathomorphology, The Regional Specialist Hospital, 10-561 Olsztyn, PolandDepartment of Human Histology and Embryology, School of Medicine, Collegium Medicum, University of Warmia and Mazury, 10-082 Olsztyn, PolandDepartment of Human Histology and Embryology, School of Medicine, Collegium Medicum, University of Warmia and Mazury, 10-082 Olsztyn, PolandBackground: 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 <i>WNT4</i> gene expression and WNT4 protein immunoreactivity (Ir) in EC, considering tumor characteristics, the clinicopathological association and estrogen dependence. Methods: <i>WNT4</i> mRNA levels were compared between benign (control) endometrium (<i>n</i> = 8) and endometroid EC (EEC) and non-endometroid EC (non-EEC) samples (<i>n</i> = 28) using the real-time PCR technique. The WNT4-Ir and ERα-Ir were evaluated by immunohistochemistry (IHC). <i>WNT4</i> 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 (<i>n</i> = 549). Results: <i>WNT4</i> gene expression was decreased in EC samples (specifically in EEC but not in non-EEC) compared to the control. The <i>WNT4</i> gene expression was also decreased in EC samples categorized by the tumor characteristics. There was no statistical difference in WNT4-Ir or ERα-Ir between the control and EC. There was no correlation between OS and <i>WNT4</i> gene expression and WNT4-Ir. Bioanalysis showed that <i>WNT4</i> and <i>ESR1</i> gene expression alterations tended to be mutually exclusive. An alteration in <i>WNT4</i> 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 <i>WNT4</i> gene has the potential to be a marker of functional estrogen signaling in EEC.https://www.mdpi.com/2072-6694/15/19/4780WNT4estrogenendometrial cancerqPCRIHC
spellingShingle Jolanta Kiewisz
Tomasz Waśniewski
Jacek Kieżun
Agnieszka Skowrońska
Monika M. Kaczmarek
Błażej Szóstak
Anna E. Kowalczyk
Zbigniew Kmieć
<i>WNT4</i> Gene and Protein Expression in Endometrial Cancer and Its Significance
Cancers
WNT4
estrogen
endometrial cancer
qPCR
IHC
title <i>WNT4</i> Gene and Protein Expression in Endometrial Cancer and Its Significance
title_full <i>WNT4</i> Gene and Protein Expression in Endometrial Cancer and Its Significance
title_fullStr <i>WNT4</i> Gene and Protein Expression in Endometrial Cancer and Its Significance
title_full_unstemmed <i>WNT4</i> Gene and Protein Expression in Endometrial Cancer and Its Significance
title_short <i>WNT4</i> Gene and Protein Expression in Endometrial Cancer and Its Significance
title_sort i wnt4 i gene and protein expression in endometrial cancer and its significance
topic WNT4
estrogen
endometrial cancer
qPCR
IHC
url https://www.mdpi.com/2072-6694/15/19/4780
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