Neuropilin-1 is a blood-based prognostic biomarker in patients with ovarian cancer

Ovarian cancer ranks as the primary contributor of death in patients with gynecological malignancies and over 70% of patients receive their diagnosis at an advanced stage.  Despite advances in treatment, a large number of ovarian cancer patients still are confronted with a poor overall prognosis. The discovery of blood-based biomarkers that can predict outcomes or provide prognostic insights is promising as findings could lead to the identification of novel drug targets and tailored treatments for ovarian cancer patients.

Neuropilin-1 is a blood-based prognostic biomarker in patients with ovarian cancer

Neuropilin-1 is a transmembrane cell-surface receptor that has been implicated in various aspects of cancer biology. It is found on the surface of cancer cells and is shed into the circulation where it can successfully be measured in blood samples with a conventional ELISA assay. Neuropilin-1 is associated with tumor progression and the formation of new blood vessels to support tumor growth is a process called angiogenesis. Neuropilin-1 interacts with molecules like vascular endothelial growth factor (VEGF) and Semaphorins promoting the survival and migration of cancer cells.

Neuropilin-1 is a blood-based prognostic biomarker in patients with ovarian cancer

The BIOMEDICA Neuropilin-1 (NRP-1) ELISA assay was highlighted in a recent study (1) showing for the first time that NRP-1 is a blood based prognostic biomarker in patients with ovarian cancer. The results encourage further research to analyse whether soluble NRP-1 could be considered as a predictive and prognostic routine tool in patients with ovarian cancer.

EASY measurement of soluble Neuropilin-1 in blood samples:

Total Soluble Neuropilin-1 ELISA | BI-20409

• Method: conventional 96-well ELISA format
• Sample volume: 10µl / well
• Sample matrix: human serum, plasma, urine, cell culture supernatant
• High homology between human NRP-1 and non-human samples –  protocol available
• Full validation package – click here 

 

Only assay that measures free and ligand bound soluble NRP1

Reference

1. Clinical impact of soluble Neuropilin-1 in ovarian cancer patients and its association with its circulating ligands of the HGF/c-MET axis.   Klotz DM, Kuhlmann JD, Link T, Goeckenjan M, Hofbauer LC, Göbel A, Rachner TD, Wimberger P. Front Oncol. 2022 Oct 21;12:974885. doi: 10.3389/fonc.2022.974885. PMID: 36338759; PMCID: PMC9635484.

 

Abstract

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.