Diagnostic value of SFRP1 as a favorable predictive and prognostic biomarker in patients with prostate cancer.

Lei Zheng,Wentao Fan,Tao Jiang,Quanlin Li,Dongchen Sun,Zhiwei Zhang,Craig N Robson

doi:10.1371/journal.pone.0118276

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.

Highlights

Prostate cancer (PCa) is a common malignant tumor of the urinary system, which is the sixth leading cause of cancer related death in men [1,2,3], seriously affects the patient’s quality of life.PLOS ONE | DOI:10.1371/journal.pone.0118276 February 26, 2015Secreted Frizzled-Related Protein-1 (SFRP1) as a Biomarker in PCaFamily history of the disease, ethnicity and advanced age are recognized as the major factors driving PCa, whereas detailed pathogenesis of this disease is still inconclusive [4]
We showed that there was a negative correlation between SFRP1 and β-catenin in human PCa tissues by evaluating clinical-pathologic features
In order to investigate their roles in PCa, we examined whether the expression of SFRP1 and β-catenin correlated with clinical-pathologic features among the 61 PCa samples by χ2 test

Summary

Introduction

SFRP1 as a Biomarker in PCa. Family history of the disease, ethnicity and advanced age are recognized as the major factors driving PCa, whereas detailed pathogenesis of this disease is still inconclusive [4]. Radical surgical resection, radiation and endocrine therapy are used as treatments of PCa [5,6,7,8]. This disease is usually fatal for most patients diagnosed in advanced stages. It is quite important to identify valuable predictive and prognostic biomarkers for early diagnosis, and to clarify the pathogenesis of PCa

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