Zhao Cheng-Hai, Bu Xian-Min, Zhang Ning
Department of Pathophysiology, School of Basic Medicine, China Medical University, Shenyang 110001, Liaoning Province, China.
World J Gastroenterol. 2007 Apr 21;13(15):2214-7. doi: 10.3748/wjg.v13.i15.2214.
To identify the methylation of secreted frizzled-related protein 1 (SFRP1) in gastric cancer and to investigate the aberrant expression of SFRP1 and its correlation with the clinical pathological features of patients.
We determined SFRP1 methylation and SFRP1 mRNA expression in 3 gastric cancer cell lines SGC-7901, BGC-823, HGC-27, from 52 primary gastric cancer specimens and matched tumor adjacent tissue specimens by methylation-specific (MSP) PCR and RT-PCR respectively. Fisher's exact test was used to analyze the statistical association between clinical pathological data and aberrant expression of SFRP1.
In 3 cancer cell lines, BGC-823 and HGC-27 had methylated SFRP1 and lost SFRP1 mRNA expression. After treatment of BGC-823 and HGC-27 with the demethylating agent, 5-aza-2'-deoxycytidine, SFRP1 was re-expressed. In 52 primary gastric cancer specimens and matched tumor adjacent tissue specimens, hypermethylation of SFRP1 was detected in 23 (44%) and 8 (15%) specimens respectively (chi(2) = 10.34, P < 0.01). Loss of SFRP1 expression was detected in 17(33%) and 6 (12%) specimens respectively (chi(2) = 6.75, P < 0.01). There was a significant correlation between SFRP1 hypermethylation and SFRP1 expression loss. SFRP1 expression was also correlated significantly with tumor stage and lymph node status, but not with patient sex, age and histological type.
SFRP1 inactivation is a common and early event caused mainly by hypermethylation in gastric cancer. SFRP1 expression loss may be correlated with tumor metastasis in primary gastric cancer.
鉴定胃癌中分泌型卷曲相关蛋白1（SFRP1）的甲基化状态，研究SFRP1的异常表达及其与患者临床病理特征的相关性。
分别采用甲基化特异性（MSP）PCR和RT-PCR技术，检测3种胃癌细胞系SGC-7901、BGC-823、HGC-27，52例原发性胃癌标本及其配对的癌旁组织标本中SFRP1的甲基化状态和SFRP1 mRNA表达。采用Fisher确切概率法分析临床病理数据与SFRP1异常表达之间的统计学关联。
在3种癌细胞系中，BGC-823和HGC-27的SFRP1发生甲基化，且SFRP1 mRNA表达缺失。用去甲基化剂5-氮杂-2'-脱氧胞苷处理BGC-823和HGC-27后，SFRP1重新表达。在52例原发性胃癌标本及其配对的癌旁组织标本中，SFRP1高甲基化分别在23例（44%）和8例（15%）标本中检测到（χ2 = 10.34，P < 0.01）。SFRP1表达缺失分别在17例（33%）和6例（12%）标本中检测到（χ2 = 6.75，P < 0.01）。SFRP1高甲基化与SFRP1表达缺失之间存在显著相关性。SFRP1表达还与肿瘤分期和淋巴结状态显著相关，但与患者性别、年龄和组织学类型无关。
SFRP1失活是胃癌中常见的早期事件，主要由高甲基化引起。原发性胃癌中SFRP1表达缺失可能与肿瘤转移相关。
