title: Spondin-2, a secreted extracellular matrix protein, is a novel diagnostic biomarker for prostate cancer.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Urology, Andrology and Kidney Transplantation Unit, Departments of Emergency and Pathological Anatomy (ST, DDC), University of Bari, Bari, Italy. Electronic address: giuseppe.lucarelli@inwind.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lucarelli
authors.forename: Monica
authors.initials: M
authors.lastname: Rutigliano
authors.forename: Carlo
authors.initials: C
authors.lastname: Bettocchi
authors.forename: Silvano
authors.initials: S
authors.lastname: Palazzo
authors.forename: Antonio
authors.initials: A
authors.lastname: Vavallo
authors.forename: Vanessa
authors.initials: V
authors.lastname: Galleggiante
authors.forename: Senia
authors.initials: S
authors.lastname: Trabucco
authors.forename: Daniela
authors.initials: D
authors.lastname: Di Clemente
authors.forename: Francesco Paolo
authors.initials: FP
authors.lastname: Selvaggi
authors.forename: Michele
authors.initials: M
authors.lastname: Battaglia
authors.forename: Pasquale
authors.initials: P
authors.lastname: Ditonno
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D016326:Extracellular Matrix Proteins / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000097:blood*; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood* / Q000175:diagnosis*; D012521:Sarcosine / Q000097:blood
chemical_list: D015415:Biomarkers; D016326:Extracellular Matrix Proteins; D009363:Neoplasm Proteins; C122166:SPON2 protein, human; D017430:Prostate-Specific Antigen; D012521:Sarcosine
keywords: DRE; NEM; PCa; PSA; SPON2; SPON2 protein; biological markers; digital rectal exploration; fPSA; free-to-total PSA ratio; human; no malignancy evidence; prostate; prostate cancer; prostate specific antigen; prostate-specific antigen; prostatic neoplasms; spondin-2