Hypermethylation of the SPARC promoter and its prognostic value for prostate cancer.

Secreted protein acidic and rich in cysteine (SPARC) is a secreted matricellular glycoprotein and plays a key role in the development of many tissues and organ types. However, the role of SPARC in prostate cancer (PCa) is still controversial. The aim of the present study was to investigate the abnormalities in the expression of SPARC and its promoter hypermethylation in prostate cancers and in correlated clinicopathological profiles. We examined the hypermethylation of the SPARC promoter as a potential mechanism for suppressing SPARC in PCa. The clinicopathological correlation between SPARC and its promoter expression and the prognostic significance of the aberrantly expressed genes were evaluated to identify novel biomarkers of PCa. SPARC expression was decreased in PCa cell lines, which correlated with hypermethylation of the SPARC promoter. Treatment with the demethylating agent 5-Aza-Cdr restored SPARC expression. Seventy percent (145 of 207) of the primary tumors exhibited SPARC hypermethylation, while only 2.6% was found in normal prostate mucosa (n = 38). In PCa cases, SPARC hypermethylation was correlated with a poorer prognosis (P = 0.005; relative risk 2.659, 95% CI, 1.433-4.562). Our findings revealed potential diagnostic markers of PCa based on specific hypermethylated CpG sites and also provided new insights of SPARC as a novel biomarker and/or treatment modality for prostate cancer.