Department of Urology, Drum Tower Clinical Medical College of Nanjing Medical University, Nanjing, Jiangsu 210008, P.R. China.
Department of Urology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, P.R. China.
Oncol Rep. 2018 Feb;39(2):659-666. doi: 10.3892/or.2017.6121. Epub 2017 Nov 29.
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.
富含半胱氨酸的酸性分泌蛋白（SPARC）是一种分泌型细胞外基质糖蛋白，在许多组织和器官类型的发育中发挥着关键作用。然而，SPARC 在前列腺癌（PCa）中的作用仍存在争议。本研究旨在研究 SPARC 及其启动子异常甲基化在前列腺癌中的表达及其与相关临床病理特征的关系。我们研究了 SPARC 启动子的高甲基化是否为抑制 PCa 中 SPARC 的潜在机制。评估了 SPARC 及其启动子表达之间的临床病理相关性以及异常表达基因的预后意义，以确定 PCa 的新型生物标志物。SPARC 在 PCa 细胞系中的表达降低，与 SPARC 启动子的高甲基化相关。用去甲基化剂 5-Aza-Cdr 处理可恢复 SPARC 的表达。70%（207 例中的 145 例）的原发肿瘤表现出 SPARC 高甲基化，而正常前列腺黏膜中仅发现 2.6%（n=38）。在 PCa 病例中，SPARC 高甲基化与预后较差相关（P=0.005；相对风险 2.659，95%CI，1.433-4.562）。我们的研究结果揭示了基于特定高甲基化 CpG 位点的 PCa 的潜在诊断标志物，并为 SPARC 作为一种新的生物标志物和/或前列腺癌的治疗方式提供了新的见解。
