Spondin-2, a Secreted Extracellular Matrix Protein, is a Novel Diagnostic Biomarker for Prostate Cancer

Abstract

SPON2 belongs to the F-spondin family of secreted extracellular matrix proteins. It is deregulated in some tumors, including prostate cancer. In this prospective study we assessed the role of serum SPON2 as a biomarker for prostate cancer diagnosis as well as any association between SPON2 levels and clinicopathological features. We also compared the diagnostic performance of this biomarker to that of serum sarcosine, and percent free-to-total and total prostate specific antigen. SPON2 was measured using a sandwich enzyme linked immunosorbent assay in serum samples from 286 patients with prostate cancer and 68 with no evidence of malignancy, as confirmed by 10 to 12-core ultrasound guided prostate biopsy. Nonparametric statistical tests and ROC analysis were done to assess the diagnostic performance of SPON2 vs the other biomarkers. Median serum SPON2 was significantly higher in patients with prostate cancer than in those with no evidence of malignancy (77.5 vs 23.6 ng/ml, p<0.0001). ROC analysis showed a higher predictive value of SPON2 (AUC 0.952) than of serum sarcosine (AUC 0.674), percent free-to-total prostate specific antigen (AUC 0.806) and total prostate specific antigen (AUC 0.561). Moreover, patients with low grade prostate cancer had higher median SPON2 levels (p=0.001). Spearman rank correlation confirmed a negative association with Gleason score (rs=-0.29, p=0.0005). We found evidence that SPON2 levels were significantly higher in patients with prostate cancer than in healthy individuals. Moreover, this biomarker had better diagnostic performance than serum sarcosine, and percent free-to-total and total prostate specific antigen. This greater accuracy was also present in a subset of patients with normal prostate specific antigen.