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

• Published in: British journal of cancer Vol. 130; no. 8; pp. 1249 - 1260
• Main Authors: Monjé, Nanna, Dragomir, Mihnea P., Sinn, Bruno V., Hoffmann, Inga, Makhmut, Anuar, Simon, Tincy, Kunze, Catarina A., Ihlow, Jana, Schmitt, Wolfgang D., Pohl, Jonathan, Piwonski, Iris, Marchenko, Sofya, Keunecke, Carlotta, Calina, Teodor G., Tiso, Francesca, Kulbe, Hagen, Kreuzinger, Caroline, Cacsire Castillo-Tong, Dan, Sehouli, Jalid, Braicu, Elena I., Denkert, Carsten, Darb-Esfahani, Silvia, Kübler, Kirsten, Capper, David, Coscia, Fabian, Morkel, Markus, Horst, David, Sers, Christine, Taube, Eliane T.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03-05-2024; Nature Publishing Group
• Subjects: 631/67/1517/1709; 692/53/2422; Biomarkers; Biomedical and Life Sciences; Biomedicine; Cancer Research; Drug Resistance; Epidemiology; Immunohistochemistry; Medical prognosis; Molecular Medicine; Multivariate analysis; Oncology; Ovarian cancer; Ovarian carcinoma; Ovaries; Signal transduction; Survival; Transcriptomics; Tumors; Wnt protein
• ISSN: 0007-0920; 1532-1827; 1532-1827
• DOI: 10.1038/s41416-023-02550-1

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.