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Evaluation of Vav3.1 as prognostic marker in endometrial cancer

M. Boesch, S. Sopper, C. Marth, H. Fiegl, A. Wiedemair, J. Rössler, J. Hatina, D. Wolf, D. Reimer, AG. Zeimet,

. 2018 ; 144 (10) : 2067-2076. [pub] 20180806

Jazyk angličtina Země Německo

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc19000490

PURPOSE: Vav3 is a guanine nucleotide exchange factor that regulates the activity of Rho/Rac family GTPases. In a study on ovarian cancer, we recently demonstrated pronounced prognostic and predictive value of Vav3.1, a specific truncation variant of the parental Vav3 gene. Here, we sought to investigate the role of Vav3.1 in the most prevalent gynecological tumor entity, endometrial cancer. METHODS: Vav3.1 transcript levels were determined in a large cohort of endometrial cancer patients using variant-specific PCR (n = 239), and non-malignant endometrial tissue served as control (n = 26). Expression levels of Vav3.1 were stratified according to established clinicopathological characteristics and correlated to long-term patient survival (average follow-up of > 7.5 years). Type 1 and type 2 cancers were separately investigated. RESULTS: While Vav3.1 was markedly overexpressed in endometrial cancer tissue, we could not detect associations with clinical parameters related to prognosis, such as FIGO stage and tumor grade. Kaplan-Meier estimators of different measures of survival failed to show prognostic significance of Vav3.1 in endometrial cancer. Lack of prognostic value was observed for both type 1 and type 2 cancers. CONCLUSIONS: Our study shows that Vav3.1 is not suited as a marker of cancer progression and/or treatment response in endometrial cancer. Feasibility and potential benefit of targeting Vav3.1 in endometrial cancer needs to be evaluated in future studies, proceeding from its clear, roughly ten-fold, induction in the malignant endometrium.

Citace poskytuje Crossref.org

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$a Boesch, Maximilian $u Lungenzentrum, Kantonsspital St. Gallen, Rorschacherstrasse 95, 9007, St. Gallen, Switzerland. Maximilian.Boesch@kssg.ch. Internal Medicine V, Medical University of Innsbruck (MUI), 6020, Innsbruck, Austria. Maximilian.Boesch@kssg.ch. Tyrolean Cancer Research Institute (TKFI), 6020, Innsbruck, Austria. Maximilian.Boesch@kssg.ch. Oncotyrol, Center for Personalized Cancer Medicine GmbH, 6020, Innsbruck, Austria. Maximilian.Boesch@kssg.ch.
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$a Evaluation of Vav3.1 as prognostic marker in endometrial cancer / $c M. Boesch, S. Sopper, C. Marth, H. Fiegl, A. Wiedemair, J. Rössler, J. Hatina, D. Wolf, D. Reimer, AG. Zeimet,
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$a PURPOSE: Vav3 is a guanine nucleotide exchange factor that regulates the activity of Rho/Rac family GTPases. In a study on ovarian cancer, we recently demonstrated pronounced prognostic and predictive value of Vav3.1, a specific truncation variant of the parental Vav3 gene. Here, we sought to investigate the role of Vav3.1 in the most prevalent gynecological tumor entity, endometrial cancer. METHODS: Vav3.1 transcript levels were determined in a large cohort of endometrial cancer patients using variant-specific PCR (n = 239), and non-malignant endometrial tissue served as control (n = 26). Expression levels of Vav3.1 were stratified according to established clinicopathological characteristics and correlated to long-term patient survival (average follow-up of > 7.5 years). Type 1 and type 2 cancers were separately investigated. RESULTS: While Vav3.1 was markedly overexpressed in endometrial cancer tissue, we could not detect associations with clinical parameters related to prognosis, such as FIGO stage and tumor grade. Kaplan-Meier estimators of different measures of survival failed to show prognostic significance of Vav3.1 in endometrial cancer. Lack of prognostic value was observed for both type 1 and type 2 cancers. CONCLUSIONS: Our study shows that Vav3.1 is not suited as a marker of cancer progression and/or treatment response in endometrial cancer. Feasibility and potential benefit of targeting Vav3.1 in endometrial cancer needs to be evaluated in future studies, proceeding from its clear, roughly ten-fold, induction in the malignant endometrium.
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$a Sopper, Sieghart $u Internal Medicine V, Medical University of Innsbruck (MUI), 6020, Innsbruck, Austria. Tyrolean Cancer Research Institute (TKFI), 6020, Innsbruck, Austria. Oncotyrol, Center for Personalized Cancer Medicine GmbH, 6020, Innsbruck, Austria.
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$a Marth, Christian $u Department of Gynecology and Obstetrics, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria.
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$a Wiedemair, Annemarie $u Department of Gynecology and Obstetrics, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria.
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$a Rössler, Julia $u Department of Gynecology and Obstetrics, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria.
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$a Hatina, Jiri $u Department of Biology and Biomedical Centre, Faculty of Medicine Pilsen, Charles University Prague, 30100, Pilsen, Czech Republic.
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$a Wolf, Dominik $u Internal Medicine V, Medical University of Innsbruck (MUI), 6020, Innsbruck, Austria. Oncotyrol, Center for Personalized Cancer Medicine GmbH, 6020, Innsbruck, Austria. Medical Clinic III, Oncology, Hematology and Rheumatology, University Clinic Bonn (UKB), 53127, Bonn, Germany.
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$a Reimer, Daniel $u Oncotyrol, Center for Personalized Cancer Medicine GmbH, 6020, Innsbruck, Austria. Department of Gynecology and Obstetrics, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria.
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$a Zeimet, Alain G $u Oncotyrol, Center for Personalized Cancer Medicine GmbH, 6020, Innsbruck, Austria. Alain.Zeimet@i-med.ac.at. Department of Gynecology and Obstetrics, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria. Alain.Zeimet@i-med.ac.at.
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