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High EVI1 and PARP1 expression as favourable prognostic markers in high-grade serous ovarian carcinoma

BACKGROUND: Mechanisms of development and progression of high-grade serous ovarian cancer (HGSOC) are poorly understood. EVI1 and PARP1, part of TGF-ß pathway, are upregulated in cancers with DNA repair deficiencies with DNA repair deficiencies and may influce disease progression and survival. There...

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Autores principales: Jank, Paul, Leichsenring, Jonas, Kolb, Svenja, Hoffmann, Inga, Bischoff, Philip, Kunze, Catarina Alisa, Dragomir, Mihnea P., Gleitsmann, Moritz, Jesinghaus, Moritz, Schmitt, Wolfgang D., Kulbe, Hagen, Sers, Christine, Stenzinger, Albrecht, Sehouli, Jalid, Braicu, Ioana Elena, Westhoff, Christina, Horst, David, Denkert, Carsten, Gröschel, Stefan, Taube, Eliane T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10388497/
https://www.ncbi.nlm.nih.gov/pubmed/37525239
http://dx.doi.org/10.1186/s13048-023-01239-6
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author Jank, Paul
Leichsenring, Jonas
Kolb, Svenja
Hoffmann, Inga
Bischoff, Philip
Kunze, Catarina Alisa
Dragomir, Mihnea P.
Gleitsmann, Moritz
Jesinghaus, Moritz
Schmitt, Wolfgang D.
Kulbe, Hagen
Sers, Christine
Stenzinger, Albrecht
Sehouli, Jalid
Braicu, Ioana Elena
Westhoff, Christina
Horst, David
Denkert, Carsten
Gröschel, Stefan
Taube, Eliane T.
author_facet Jank, Paul
Leichsenring, Jonas
Kolb, Svenja
Hoffmann, Inga
Bischoff, Philip
Kunze, Catarina Alisa
Dragomir, Mihnea P.
Gleitsmann, Moritz
Jesinghaus, Moritz
Schmitt, Wolfgang D.
Kulbe, Hagen
Sers, Christine
Stenzinger, Albrecht
Sehouli, Jalid
Braicu, Ioana Elena
Westhoff, Christina
Horst, David
Denkert, Carsten
Gröschel, Stefan
Taube, Eliane T.
author_sort Jank, Paul
collection PubMed
description BACKGROUND: Mechanisms of development and progression of high-grade serous ovarian cancer (HGSOC) are poorly understood. EVI1 and PARP1, part of TGF-ß pathway, are upregulated in cancers with DNA repair deficiencies with DNA repair deficiencies and may influce disease progression and survival. Therefore we questioned the prognostic significance of protein expression of EVI1 alone and in combination with PARP1 and analyzed them in a cohort of patients with HGSOC. METHODS: For 562 HGSOC patients, we evaluated EVI1 and PARP1 expression by immunohistochemical staining on tissue microarrays with QuPath digital semi-automatic positive cell detection. RESULTS: High EVI1 expressing (> 30% positive tumor cells) HGSOC were associated with improved progression-free survival (PFS) (HR = 0.66, 95% CI: 0.504–0.852, p = 0.002) and overall survival (OS) (HR = 0.45, 95% CI: 0.352–0.563, p < 0.001), including multivariate analysis. Most interestingly, mutual high expression of both proteins identifies a group with particularly good prognosis. Our findings were proven technically and clinically using bioinformatical data sets for single-cell sequencing, copy number variation and gene as well as protein expression. CONCLUSIONS: EVI1 and PARP1 are robust prognostic biomarkers for favorable prognosis in HGSOC and imply further research with respect to their reciprocity. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13048-023-01239-6.
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spelling pubmed-103884972023-08-01 High EVI1 and PARP1 expression as favourable prognostic markers in high-grade serous ovarian carcinoma Jank, Paul Leichsenring, Jonas Kolb, Svenja Hoffmann, Inga Bischoff, Philip Kunze, Catarina Alisa Dragomir, Mihnea P. Gleitsmann, Moritz Jesinghaus, Moritz Schmitt, Wolfgang D. Kulbe, Hagen Sers, Christine Stenzinger, Albrecht Sehouli, Jalid Braicu, Ioana Elena Westhoff, Christina Horst, David Denkert, Carsten Gröschel, Stefan Taube, Eliane T. J Ovarian Res Research BACKGROUND: Mechanisms of development and progression of high-grade serous ovarian cancer (HGSOC) are poorly understood. EVI1 and PARP1, part of TGF-ß pathway, are upregulated in cancers with DNA repair deficiencies with DNA repair deficiencies and may influce disease progression and survival. Therefore we questioned the prognostic significance of protein expression of EVI1 alone and in combination with PARP1 and analyzed them in a cohort of patients with HGSOC. METHODS: For 562 HGSOC patients, we evaluated EVI1 and PARP1 expression by immunohistochemical staining on tissue microarrays with QuPath digital semi-automatic positive cell detection. RESULTS: High EVI1 expressing (> 30% positive tumor cells) HGSOC were associated with improved progression-free survival (PFS) (HR = 0.66, 95% CI: 0.504–0.852, p = 0.002) and overall survival (OS) (HR = 0.45, 95% CI: 0.352–0.563, p < 0.001), including multivariate analysis. Most interestingly, mutual high expression of both proteins identifies a group with particularly good prognosis. Our findings were proven technically and clinically using bioinformatical data sets for single-cell sequencing, copy number variation and gene as well as protein expression. CONCLUSIONS: EVI1 and PARP1 are robust prognostic biomarkers for favorable prognosis in HGSOC and imply further research with respect to their reciprocity. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13048-023-01239-6. BioMed Central 2023-07-31 /pmc/articles/PMC10388497/ /pubmed/37525239 http://dx.doi.org/10.1186/s13048-023-01239-6 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Jank, Paul
Leichsenring, Jonas
Kolb, Svenja
Hoffmann, Inga
Bischoff, Philip
Kunze, Catarina Alisa
Dragomir, Mihnea P.
Gleitsmann, Moritz
Jesinghaus, Moritz
Schmitt, Wolfgang D.
Kulbe, Hagen
Sers, Christine
Stenzinger, Albrecht
Sehouli, Jalid
Braicu, Ioana Elena
Westhoff, Christina
Horst, David
Denkert, Carsten
Gröschel, Stefan
Taube, Eliane T.
High EVI1 and PARP1 expression as favourable prognostic markers in high-grade serous ovarian carcinoma
title High EVI1 and PARP1 expression as favourable prognostic markers in high-grade serous ovarian carcinoma
title_full High EVI1 and PARP1 expression as favourable prognostic markers in high-grade serous ovarian carcinoma
title_fullStr High EVI1 and PARP1 expression as favourable prognostic markers in high-grade serous ovarian carcinoma
title_full_unstemmed High EVI1 and PARP1 expression as favourable prognostic markers in high-grade serous ovarian carcinoma
title_short High EVI1 and PARP1 expression as favourable prognostic markers in high-grade serous ovarian carcinoma
title_sort high evi1 and parp1 expression as favourable prognostic markers in high-grade serous ovarian carcinoma
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10388497/
https://www.ncbi.nlm.nih.gov/pubmed/37525239
http://dx.doi.org/10.1186/s13048-023-01239-6
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