Urinary nerve growth factor as an oncologic biomarker for prostate cancer aggressiveness

Abstract

Objectives: We investigated urinary nerve growth factor (NGF) as a novel urinary biomarker for high-grade prostate cancer (PCa).

Methods and materials: After institutional review board approval for a prospective pilot study, we enrolled men at the preoperative visit before robotic-assisted radical prostatectomy. Demographics, urinary flow parameters, and urine samples were collected. Urinary NGF and urinary creatinine were obtained in the translational science laboratory. Pathologic and postoperative demographics were collected after surgery. NGF is the primary outcome variable (dependent variable). The pathologic Gleason score (ordinal variable ≤6, 7, and ≤8) served as an independent grouping variable. Multivariate analysis using a general linear model was conducted to investigate associations between independent variables and NGF (dependent variable) after adjusting for urinary concentration and volume.

Results: We enrolled and analyzed urine samples and pathologic data from 115 subjects. Patient pathology included 24% (n = 28) Gleason score 6 or less, 68% (n = 78) Gleason score 7, and 8% (n = 9) Gleason score 8 or greater. Perineural invasion was more prevalent in higher-grade disease (P<0.001). The median NGF level was 24.1 pg/ml (range: 0.16-270.5 pg/ml) and was transformed to the log base 10 scale. Total bladder volume, urinary creatinine level, prostate-specific antigen level, and diabetes were correlated with the Log NGF. In a general linear model, adjusting for bladder volume and urinary creatinine, increasing Log10 NGF was associated with higher Gleason score (Gleason category ≤6, 7, and ≥8; P = 0.003).

Conclusions: Urinary NGF may be a biomarker for higher-grade PCa. Our pilot study suggests further investigation is warranted to determine whether urinary NGF could provide unique additional information in patients with PCa.

Keywords: Biomarker; Gleason score; Neurogenesis; Prostate cancer.