Einfluss der Expression von Markern der Epithelial-Mesenchymalen Transition auf das klinische Überleben von Ovarialkarzinom-Patientinnen
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Philipps-Universität Marburg
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Abstract
With a five-year survival rate in advanced stages of only 20%, ovarian cancer is, along with breast cancer, the most frequently fatal gynecological cancer. This is due, among other things, to the fact that ovarian cancer is usually only diagnosed in the late stage, when metastases are already present [Robert Koch Institute 2021]. An important process in this metastasis is the epithelial-mesenchymal transition, during which the tumor cells lose their epithelial phenotype, assume a mesenchymal form and metastasize in this form. In the distant organ, the reverse process - the mesenchymal-epithelial transition – takes place and the cells again assume a more stable, epithelial phenotype. This is accompanied by an up- and down- regulation of multiple molecules [Brabletz et al. 2005; Chaffer et al. 2007; Thiery et al. 2009; Brabletz et al. 2021].
In this study, the expression of three EMT markers (TWIST, actin and vimentin) and four MET markers (occludin, BerEP4, E-cadherin and CK-18) is measured in the tissue of 80 patients with ovarian cancer. It is quantified in the tissue of the cancer itself and on the other hand in the tissue of the metastasis in the omentum. The present work is one of the first in which, in addition to the tissue of the primary tumor, metastatic tissue was also included in the study. The marker expression was then correlated with the progression-free survival of the patients as well as the clinical markers CRP and BMI.
A significance in correlation with progression-free survival was shown for the EMT marker vimentin in the tissue of the primary tumor. With low expression of vimentin in the ovary, the median PFS was 60.7 months, while with high expression of vimentin in the ovary it was
84.5 months. TWIST showed a significant correlation with body mass index, while E- cadherin even showed significance with both clinical parameters.
In this work, EMT was expected to occur in the primary tumor and MET in the metastasis. During EMT, epithelial markers should be up-regulated and mesenchymal markers should be down-regulated; during MET, conversely, mesenchymal markers should be up-regulated and epithelial markers should be down-regulated. However, it has been shown that EMT/MET is a transient and dynamic process during which endpoints on the fully epithelial or fully mesenchymal side are rarely reached. Rather, within the framework of EMT - which often only takes place partially - there are multiple intermediate stages that can be passed through in rapid succession and some of which also appear to be very carcinogenic [Kröger et al. 2019; Brabletz et al. 2021]. In order to be able to better map these carcinogenic hybrid stages and ultimately attack them in a more optimized way, a suitable combined selection of EMT and MET markers should be used in the future instead of individual markers [Armstrong e al. 2011; Huang et al. 2013; Tan et al. 2014; Guo et al. 2018]. In the current literature and the present work it has emerged that there is a greater similarity between primary tumor and metastasis than initially assumed [Blechschmidt et al. 2008; Köbel et al. 2011; Spizzo et al. 2011]. With regard to EMT/MET markers, an additional examination of ascites as a medium for metastasis of ovarian cancer might be helpful. In addition, within the framework of EMT research, the methodology must be standardized in the future so that better comparability can be guaranteed. In future studies, possibly with a larger patient population, the findings presented in this work can be built upon.
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Created: 2025Issued: 2025-06-04Updated: 2025-06-04
Faculty
Medizin
Publisher
Philipps-Universität Marburg
Language
ger
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DoctoralThesis
Keywords
ovarian cancerepithelial-mesenchymal transitionemt
DFG-subjects
EMTEpithelial-Mesenchymale TransitionOvarialkarzinom
DDC-Numbers
610
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Meyer, Jasmin: Einfluss der Expression von Markern der Epithelial-Mesenchymalen Transition auf das klinische Überleben von Ovarialkarzinom-Patientinnen. : Philipps-Universität Marburg 2025-06-04. DOI: https://doi.org/10.17192/z2025.0203.
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