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

Abstract

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 SFRP1 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.

Prognostic and predictive biomarkers in prostate cancer

“…Therefore, SFRP1 expression, which inversely correlates with the expression of β-catenin, appears to be a favorable prognostic biomarker in PCa. [23] In accordance 210 with these findings, restoration of normal SFRP1 levels in PCa cell lines treated with genisteinachieved through DNA methylation or histone modificationsreduced their proliferation, invasion and migration potential. [24] Similarly, a combination of DNA demethylation and EZH2 inhibition managed 215…”

Prognostic Relevance of SFRP1 Gene Promoter Methylation in Colorectal Carcinoma

“…MGMT in Gliomas (Weller et al, 2010). Some studies have also described value of SFRP1 as prognostic/predictive biomarker in cancer (Leygo et al, 2017;Zheng et al, 2015). The aim of our study was to look for promoter hypermethylation of SFRP1 gene in CRC, and find its prognostic significance.…”

Epigenetics of SFRP1: The Dual Roles in Human Cancers

“…SFRP1 negatively regulates AR through the CRD motif and binds with the Fz receptor to form SFRP1/Fz complexes. The inactivation of SFRP1 leads to the uncontrolled AR activation, which is involved in the pathogenesis of prostate cancer [87].…”