Soluble Neuropilin-1 is an independent marker of poor prognosis in early breast cancer

Abstract

Background: Neuropilin-1 (NRP-1) is a transmembrane protein that acts as a multifunctional non-tyrosine kinase receptor with an established role in development and immunity. NRP-1 also regulates tumor biology, and high expression levels of tissue NRP-1 have been associated with a poor prognosis. Recently, ELISA-based quantification of soluble NRP-1 (sNRP-1) has become available, but little is known about the prognostic value of sNRP-1 in malignancies.

Materials and methods: We measured sNRP-1 in the serum of 509 patients with primary early breast cancer (BC) at the time of diagnosis using ELISA.

Results: Mean serum values of sNRP-1 were 1.88 ± 0.52 nmol/l (= 130.83 ± 36.24 ng/ml). SNRP-1 levels weakly correlated with age, and were higher in peri- and postmenopausal patients compared to premenopausal patients, respectively (p < 0.0001). Low levels of sNRP-1 were associated with a significant survival benefit compared to high sNRP-1 levels at baseline (p = 0.005; HR 1.94; 95%CI 1.23-3.06). These findings remained significant after adjustment for tumor stage including lymph node involvement, grading, hormone receptor, HER2 status, and age (p = 0.022; HR 1.78; 95%CI 1.09-2.91).

Conclusion: Our findings warrant further investigations into the prognostic and therapeutic potential of sNRP-1 in BC.

Keywords: Breast cancer; Neuropilin-1; Prognosis.

Fig. 1

sNRP-1 levels weakly correlate with age. sNRP-1 serum levels positively correlate with the age of assessed subjects

Fig. 2

sNRP-1 is a prognostic marker for breast cancer-specific survival. Baseline levels of sNRP-1 were measured in 506 patients diagnosed with primary, non-metastatic breast cancer using ELISA. The patient cohort was divided at the median into a sNRP-1^high and sNRP-1^low group. Kaplan–Meier curve for breast cancer-specific survival (BCSS) was assessed using the log-rank (Mantel-Cox) test based on survival data of 501 patients

Fig. 3

sNRP-1 is an independent prognostic marker in breast cancer. Univariate and multivariate Cox regression analyses for BCSS dependent on sNRP-1 levels and clinicopathological parameters were performed. Multivariate analyses adjusted for tumor stage (T), lymph node involvement (N), grade (G) and the expression of estrogen, progesterone receptor and HER2 as well as age confirmed the independent prognostic value of sNRP-1 in breast cancer. All included parameters were used in a binominal fashion (sNRP-1: high vs low; tumor stage: pT4, pT3, pT2 vs pT1; lymph node involvement: positive vs negative; grade: III, II vs I; hormone receptor and HER2 status: positive vs negative; age: > 60 vs < 60)