Clinical impact of soluble Neuropilin-1 in ovarian cancer patients and its association with its circulating ligands of the HGF/c-MET axis

• Verfasst von: Klotz, Daniel Martin [VerfasserIn]
• Verfasst von: Kuhlmann, Jan Dominik [VerfasserIn]
• Verfasst von: Link, Theresa [VerfasserIn]
• Verfasst von: Goeckenjan, Maren [VerfasserIn]
• Verfasst von: Hofbauer, Lorenz C. [VerfasserIn]
• Verfasst von: Göbel, Andy [VerfasserIn]
• Verfasst von: Rachner, Tilman D. [VerfasserIn]
• Verfasst von: Wimberger, Pauline [VerfasserIn]
• Titel: Clinical impact of soluble Neuropilin-1 in ovarian cancer patients and its association with its circulating ligands of the HGF/c-MET axis
• Verf.angabe: Daniel Martin Klotz, Jan Dominik Kuhlmann, Theresa Link, Maren Goeckenjan, Lorenz C. Hofbauer, Andy Göbel, Tilman D. Rachner and Pauline Wimberger
• E-Jahr: 2022
• Jahr: 21 October 2022
• Umfang: 10 S.
• Fussnoten: Gesehen am 11.01.2023
• Titel Quelle: Enthalten in: Frontiers in oncology
• Ort Quelle: Lausanne : Frontiers Media, 2011
• Jahr Quelle: 2022
• Band/Heft Quelle: 12(2022) vom: Okt., Artikel-ID 974885, Seite 1-10
• ISSN Quelle: 2234-943X
• DOI: doi:10.3389/fonc.2022.974885
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1830824430

Abstract

BackgroundNeuropilin (NRP) is a transmembrane protein, which has been shown to be a pro-angiogenic mediator and implicated as a potential driver of cancer progression. NRP-1 up-regulation in ovarian cancer tissue predicts poor prognosis. However, the clinical relevance of the soluble form of NRP-1 (sNRP-1) as a circulating biomarker in ovarian cancer patients is unknown.Methods/patients cohortsNRP-1 levels were quantified in a cohort of 88 clinically documented ovarian cancer patients by a commercially available sNRP-1 enzyme-linked immunosorbent assay (ELISA) kit (Biomedica, Vienna, Austria). Patients (81.8% with FIGOIII/IV) received primary cytoreductive surgery with the aim of macroscopic complete resection (achieved in 55.7% of patients) and the recommendation of adjuvant chemotherapy in line with national guidelines.ResultsHigher levels of sNRP-1 reflected more advanced disease (FIGO III/IV) and indicated a trend towards suboptimal surgical outcome, i.e. any residual tumor. sNRP-1 was neither related to the patients’ age nor the BRCA1/2 mutational status. Patients with higher sNRP-1 levels at primary diagnosis had a significantly reduced progression-free survival (PFS) (HR = 0.541, 95%CI: 0.304 - 0.963; p = 0.037) and overall survival (OS) (HR = 0.459, 95%CI: 0.225 - 0.936; p = 0.032). Principal component analysis showed that sNRP-1 levels were unrelated to the circulating hepatocyte growth factor (HGF) and the soluble ectodomain of its receptor the tyrosine kinase mesenchymal-epithelial transition (c-MET), suggesting that there is no proportional serological concentration gradient of soluble components of the NRP-1/HGF/c-MET signaling axis.ConclusionsIn line with the previously shown tissue-based prognostic role, we demonstrated for the first time that sNRP-1 can also act as a readily accessible, prognostic biomarker in the circulation of patients with ovarian cancer at primary diagnosis. Given its known role in angiogenesis and conferring resistance to the poly ADP-ribose polymerase (PARP) inhibitor olaparib in vitro, our results encourage more detailed investigation into sNRP-1 as a potential predictive biomarker for bevacizumab and/or PARP-inhibitor treatment.