Diagnostic Value of SFRP1 as a Favorable Predictive and Prognostic Biomarker in Patients with Prostate Cancer

<div><p>Growing genetic and molecular biological evidence suggests that the disruption of balance between Secreted Frizzled-Related Protein-1 (SFRP1) and β-catenin plays an important role in the initiation and development of multiple cancers. The aim of this study was to examine whether the expression of SFRP1 and β-catenin is associated with the clinical-pathologic features of patients with prostate cancer (PCa), and to evaluate their potential roles as predictive and prognostic biomarkers. In this study, a total of 61 patients with PCa and 10 patients with benign prostatic hyperplasia were included, and we showed that the expression of SFRP1 and β-catenin was correlated with the Gleason score, survival rate and response for endocrine therapy of PCa. The survival rates of PCa patients with low SFRP1 expression (P = 0.016) or high β-catenin expression (P = 0.004) were significantly poorer. A negative correlation (r = -0.275, P = 0.032) between SFRP1 and β-catenin was observed by Chi-square test. Multivariate analysis suggested that SFRP1 (hazard ratio, 0.429; 95% confidence intervals, 0.227–0.812; P = 0.009) may serve as an independent predictive and prognostic factor for PCa. We also showed that the protein and mRNA levels of SFRP1 in androgen-dependent PCa cell line LNCaP were significantly higher than those in androgen-independent PCa cell lines DU145 and PC3. However, the protein level of β-catenin in LNCaP cells was significantly lower than that in DU145 and PC3 cells, and no significant difference of β-catenin mRNA level was observed in LNCaP, DU145 and PC3 cells. Bisulfite sequencing PCR assay revealed significantly lower methylation level of <i>SFRP1</i> promoter in LNCaP cells than that in DU145 and PC3 cells. Taken together, these findings suggest that SFRP1, which expression inversely correlates with that of β-catenin, is a favorable predictive and prognostic biomarker.</p>