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Title:Vpliv signalizacije Wnt in epitelijsko-mezenhimske tranzicije na značilnost raka endometrija
Authors:ID Ledinek Štosir, Živa (Author)
ID Knez, Jure (Mentor) More about this mentor... New window
Files:.pdf DOK_Ledinek_Stosir_Ziva_2026.pdf (3,22 MB)
MD5: BD083CA36F4048DD6AF0E15B39CEB3C8
 
Language:Slovenian
Work type:Dissertation
Typology:2.08 - Doctoral Dissertation
Organization:MF - Faculty of Medicine
Abstract:Karcinom endometrija je najpogostejši ginekološki rak v razvitem svetu. Ker za to boleznijo letno umre vse več žensk, je pomembno, da razumemo mehanizme, ki zvišujejo tveganje za ponovitev bolezni. To je temelj za izbiro učinkovitega zdravljenja. Pomembno vlogo pri nastanku in napredovanju karcinoma endometrija ima aktivacija signalne poti Wnt, ki vodi v prepisovanje genov, ki regulirajo celični cikel. Signalna pot Wnt med drugim vodi k aktivaciji procesa epitelijsko-mezenhimske tranzicije (EMT), ki rakavim celicam omogoča migracijo in s tem zasevanje. V doktorski nalogi smo primerjali izražanje označevalcev signalne poti Wnt in EMT z izražanjem hormonskih receptorjev v tumorskih celicah in s klinično-patološkimi značilnostmi bolnic. S tem bi lahko na klinično uporaben način predvideli, ali je v tumorskih celicah prišlo do sprememb, ki pomenijo večje tvega-nje za napredovanje bolezni. V prospektivno kohortno raziskavo je bilo vključenih 65 bolnic s karcinomom endometrija, pri katerih smo z izvedbo imunohistokemičnih reakcij na parafinskih rezinah tumorskega tkiva vrednotili izražanje hormonskih receptorjev, označevalcev aktivacije signalne poti Wnt (β-katenina), antagonista Wnt (Dkk1) in označeval-cev EMT (E-kadherin, N-kadherin). Rezultate imunohistokemičnih reakcij za posamezne označevalce smo primerjali med seboj in s klinično-patološkimi lastnostmi tumorjev. Ugotovili smo, da je izražanje označevalcev Wnt in EMT koreliralo z izražanjem hormonskih receptorjev in ne z drugimi lastnostmi tumorjev. Izražanje antagonista Wnt, Dkk1, se je značilno razlikovalo med skupinami bolnic, ki se po smernicah ESGO/ESTRO/ESP razlikujejo v prognozi bolezni. Z rezultati naše raziskave bomo pripomogli k boljšemu razume-vanju povezave med signalno potjo Wnt in EMT ter odpirajo možnosti za nadaljnje preučevanje vloge Wnt antagonista Dkk1 v napredovanju bolezni, vključno z možnostjo razvoja tarčne terapije, ki vpliva na preučevane signalne poti.
Keywords:signalna pot Wnt, EMT (epitelijsko-mezenhimska tranzicija), karcinom endometrija, imunohistokemični označevalci
Place of publishing:Maribor
Publisher:[Ž. Ledinek Štosir]
Year of publishing:2026
PID:20.500.12556/DKUM-95936 New window
UDC:618.14-006+616-033.2:577.2(043.3)
COBISS.SI-ID:273585923 New window
Publication date in DKUM:30.03.2026
Views:204
Downloads:20
Metadata:XML DC-XML DC-RDF
Categories:MF
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Licences

License:CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
Link:http://creativecommons.org/licenses/by-nc-nd/4.0/
Description:The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.
Licensing start date:12.11.2025

Secondary language

Language:English
Title:The association of Wnt-signalling and EMT markers with clinical characteristics in women with endometrial cancer
Abstract:Endometrial carcinoma is the most common gynaecologic malignancy in the developed world. In order to have an efficient approach to treatment it is important to accurately predict the disease prognosis by considering molecular mechanisms causing disease progression. Upregulated Wnt signalling plays an important role in endometrial carcinoma initiation and progression and also by activating epithelial-to-mesenchymal transition (EMT) in tumour cells, causing the expression of mesenchymal markers, and enabling tumour cells to dissociate and migrate. The purpose of our study was to compare expression of Wnt and EMT markers with hormone receptor status and other clinico-pathological characteristics of tumours. We aimed to propose a clinically useful method to assess the risk of disease progression. Our prospective cohort study included 65 patients with endometrial carcinoma. We analysed expression of hormone receptors, markers of Wnt signalling (β-catenin), Wnt antagonist (DKK1) and EMT markers (E-cadherin, N-cadherin) on formalin fixed paraffin embedded tissue samples using im-munohistochemistry. We compared the results of immunohistochemical staining between the studied markers and with clinico-pathological data. Wnt signalling and EMT markers were significantly correlated with hormone receptors status in endometrial carcinoma, but not with other clinico-pathological characteristics. Expression of Wnt antagonist, Dkk1 was significantly different between the ESGO/ESTRO/ESP patient risk assessment categories using integrated molecular risk assessment. Our results contribute to better understanding of correlation between Wnt signalling and EMT. They offer new insights into the role of Dkk1 as Wnt antagonist and potential target for future development of targeted treatment options for endometrial carcinoma.
Keywords:Wnt pathway, EMT (epithelial to mesenchymal transformation), endometrial carcino-ma, immunohistochemical markers


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