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

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Item Type:Article
Title:AHRR and SFRP2 in primary versus recurrent high-grade serous ovarian carcinoma and their prognostic implication
Creators Name:Monjé, N. and Dragomir, M.P. and Sinn, B.V. and Hoffmann, I. and Makhmut, A. and Simon, T. and Kunze, C.A. and Ihlow, J. and Schmitt, W.D. and Pohl, J. and Piwonski, I. and Marchenko, S. and Keunecke, C. and Calina, T.G. and Tiso, F. and Kulbe, H. and Kreuzinger, C. and Cacsire Castillo-Tong, D. and Sehouli, J. and Braicu, E.I. and Denkert, C. and Darb-Esfahani, S. and Kübler, K. and Capper, D. and Coscia, F. and Morkel, M. and Horst, D. and Sers, C. and Taube, E.T.
Abstract: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.
Keywords:Basic Helix-Loop-Helix Transcription Factors, Tumor Biomarkers, Serous Cystadenocarcinoma, Gene Expression Profiling, Membrane Proteins, Ovarian Neoplasms, Prognosis, Repressor Proteins
Source:British Journal of Cancer
Publisher:Nature Publishing Group
Page Range:1249-1260
Date:3 May 2024
Official Publication:https://doi.org/10.1038/s41416-023-02550-1
PubMed:View item in PubMed

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