AHRR and SFRP2 in primary versus recurrent high-grade serous ovarian carcinoma and their prognostic implication.

Autor: Monjé N; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Pathology, Charitéplatz 1, 10117, Berlin, Germany., Dragomir MP; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Pathology, Charitéplatz 1, 10117, Berlin, Germany.; German Cancer Consortium (DKTK), Partner Site Berlin, and German Cancer Research Center (DKFZ), Heidelberg, Germany.; Berlin Institute of Health (BIH), Berlin, Germany., Sinn BV; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Pathology, Charitéplatz 1, 10117, Berlin, Germany., Hoffmann I; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Pathology, Charitéplatz 1, 10117, Berlin, Germany., Makhmut A; Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC), Spatial Proteomics Group, Berlin, Germany., Simon T; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Pathology, Charitéplatz 1, 10117, Berlin, Germany., Kunze CA; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Pathology, Charitéplatz 1, 10117, Berlin, Germany., Ihlow J; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Pathology, Charitéplatz 1, 10117, Berlin, Germany.; Berlin Institute of Health (BIH), Berlin, Germany., Schmitt WD; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Pathology, Charitéplatz 1, 10117, Berlin, Germany., Pohl J; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Pathology, Charitéplatz 1, 10117, Berlin, Germany., Piwonski I; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Pathology, Charitéplatz 1, 10117, Berlin, Germany., Marchenko S; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Pathology, Charitéplatz 1, 10117, Berlin, Germany., Keunecke C; Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department for Gynecology with the Center for Oncologic Surgery Charité Campus Virchow-Klinikum, Charitéplatz 1, 10117, Berlin, Germany., Calina TG; TGC Ventures UG, Berlin, Germany., Tiso F; Center of Functional Genomics, Berlin Institute of Health at Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.; Department of Hematology, Oncology and Cancer Immunology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Hindenburgdamm 30, 12203, Berlin, Germany., Kulbe H; Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department for Gynecology with the Center for Oncologic Surgery Charité Campus Virchow-Klinikum, Charitéplatz 1, 10117, Berlin, Germany., Kreuzinger C; Translational Gynecology Group, Department of Obstetrics and Gynecology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria., Cacsire Castillo-Tong D; Translational Gynecology Group, Department of Obstetrics and Gynecology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria., Sehouli J; German Cancer Consortium (DKTK), Partner Site Berlin, and German Cancer Research Center (DKFZ), Heidelberg, Germany.; Berlin Institute of Health (BIH), Berlin, Germany.; Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department for Gynecology with the Center for Oncologic Surgery Charité Campus Virchow-Klinikum, Charitéplatz 1, 10117, Berlin, Germany., Braicu EI; German Cancer Consortium (DKTK), Partner Site Berlin, and German Cancer Research Center (DKFZ), Heidelberg, Germany.; Berlin Institute of Health (BIH), Berlin, Germany.; Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department for Gynecology with the Center for Oncologic Surgery Charité Campus Virchow-Klinikum, Charitéplatz 1, 10117, Berlin, Germany., Denkert C; Institute of Pathology, University Hospital Gießen and Marburg, Marburg, Germany., Darb-Esfahani S; Institute of Pathology, Berlin-Spandau, Stadtrandstraße 555, 13589, Berlin, Germany., Kübler K; German Cancer Consortium (DKTK), Partner Site Berlin, and German Cancer Research Center (DKFZ), Heidelberg, Germany.; Center of Functional Genomics, Berlin Institute of Health at Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.; Department of Hematology, Oncology and Cancer Immunology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Hindenburgdamm 30, 12203, Berlin, Germany.; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School Teaching Hospital, Charlestown, MA, USA., Capper D; German Cancer Consortium (DKTK), Partner Site Berlin, and German Cancer Research Center (DKFZ), Heidelberg, Germany.; Department of Neuropathology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany., Coscia F; Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC), Spatial Proteomics Group, Berlin, Germany., Morkel M; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Pathology, Charitéplatz 1, 10117, Berlin, Germany.; German Cancer Consortium (DKTK), Partner Site Berlin, and German Cancer Research Center (DKFZ), Heidelberg, Germany.; Berlin Institute of Health (BIH), Berlin, Germany., Horst D; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Pathology, Charitéplatz 1, 10117, Berlin, Germany.; German Cancer Consortium (DKTK), Partner Site Berlin, and German Cancer Research Center (DKFZ), Heidelberg, Germany.; Berlin Institute of Health (BIH), Berlin, Germany., Sers C; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Pathology, Charitéplatz 1, 10117, Berlin, Germany.; German Cancer Consortium (DKTK), Partner Site Berlin, and German Cancer Research Center (DKFZ), Heidelberg, Germany.; Berlin Institute of Health (BIH), Berlin, Germany., Taube ET; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Pathology, Charitéplatz 1, 10117, Berlin, Germany. eliane.taube@charite.de.
Jazyk: angličtina
Zdroj: British journal of cancer [Br J Cancer] 2024 May; Vol. 130 (8), pp. 1249-1260. Date of Electronic Publication: 2024 Feb 09.
DOI: 10.1038/s41416-023-02550-1
Abstrakt: Background: The aim of this study was to analyse transcriptomic differences between primary and recurrent high-grade serous ovarian carcinoma (HGSOC) to identify prognostic biomarkers.
Methods: We analysed 19 paired primary and recurrent HGSOC samples using targeted RNA sequencing. We selected the best candidates using in silico survival and pathway analysis and validated the biomarkers using immunohistochemistry on a cohort of 44 paired samples, an additional cohort of 504 primary HGSOCs and explored their function.
Results: We identified 233 differential expressed genes. Twenty-three showed a significant prognostic value for PFS and OS in silico. Seven markers (AHRR, COL5A2, FABP4, HMGCS2, ITGA5, SFRP2 and WNT9B) were chosen for validation at the protein level. AHRR expression was higher in primary tumours (p < 0.0001) and correlated with better patient survival (p < 0.05). Stromal SFRP2 expression was higher in recurrent samples (p = 0.009) and protein expression in primary tumours was associated with worse patient survival (p = 0.022). In multivariate analysis, tumour AHRR and SFRP2 remained independent prognostic markers. In vitro studies supported the anti-tumorigenic role of AHRR and the oncogenic function of SFRP2.
Conclusions: Our results underline the relevance of AHRR and SFRP2 proteins in aryl-hydrocarbon receptor and Wnt-signalling, respectively, and might lead to establishing them as biomarkers in HGSOC.
(© 2024. The Author(s).)
Databáze: MEDLINE
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