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

Background: Neuropilin (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 cohort: sNRP-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. - Results: Higher 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. - Conclusions: In 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.

Identiferoai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:91526
Date06 June 2024
CreatorsKlotz, Daniel Martin, Kuhlmann, Jan Dominik, Link, Theresa, Goeckenjan, Maren, Hofbauer, Lorenz C., Göbel, Andy, Rachner, Tilman D., Wimberger, Pauline
PublisherFrontiers Media
Source SetsHochschulschriftenserver (HSSS) der SLUB Dresden
LanguageEnglish
Detected LanguageEnglish
Typeinfo:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text
Rightsinfo:eu-repo/semantics/openAccess
Relation2234-943X, 10.3389/fonc.2022.974885

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