Wnt通路拮抗基因SFRP1 SFRP2 SFRP4 SFRP5甲基化状态与肾透明细胞癌关系的研究

Aberrant Promoter Methylation of SFRPs,the Antagonists in Renal Clear Cell Carcinoma

目的:研究SFRPs家族中SFRP1、SFRP2、SFRP4、SFRP5基因启动子区甲基化状况,探讨基因的甲基化与肾透明细胞癌发生发展的关系。方法:采用甲基化特异性PCR(methylation specific PCR,MSP)方法检测66例肾透明细胞癌及30例癌旁组织中SFRP1、SFRP2、SFRP4、SFRP5基因启动子区甲基化状态及其与临床病理学资料之间的关系。结果:肾透明细胞癌组织中SFRP1、SFRP2、SFRP4、SFRP5基因甲基化率分别为77.3%(51/66)、72.7%(48/66)、59.1%(39/66)、69.7%(46/66),均显著高于相应的癌旁组织,结果有统计学意义(P<0.05)。与临床病理学资料相联系,肾透明细胞癌组织中SFRP1、SFRP5基因甲基化与肿瘤TNM分期相关;SFRP4基因甲基化与肿瘤的病理学分级相关(P<0.05)。结论:SFRP1、SFRP2、SFRP4、SFRP5基因的甲基化均可能参与肾透明细胞癌的发生。SFRP1、SFRP5基因甲基化可能与肾透明细胞癌的发展,浸润和转移有关。SFRP4基因甲基化可能与肾透明细胞癌的恶性行为有关。

Objective： To investigate the promoter methylation status of SFRP1, SFRP2, SFRP4, and SFRP5 genes in renal clearcell carcinoma （ CCRCC ） as well as to discuss the relationship between the methylation of genes and development of CCRCC. Methods： Methylation-specific polymerase chain reaction method was used to examine the methylation status of the 5＇ CpG island of SFRP1, SFRP2, SFRP4, and SFRP5 genes in 66 cases with CCRCC and 30 with paraneoplastic tissues. Related clinical data were analyzed. Results： Methylation frequency rates of SFRPI, SFRP2, SFRP4, and SFRP5 in CCRCC were 77.3% （ 51/66 ）, 72.7% （ 48/66 ）, 59.1% （ 39/66 ）, and 69.7% （ 46/66 ）, respectively, significantly higher than those in the paraneoplastic tissues （ P 〈 0.05 ）. Methylation status of SFRP1 and SFRP5 genes in CCRCC was related to TNM staging, whereas SFRP4 was correlated with tumor grading （ P 〈 0.05 ）. Conclusion： Methylation of SFRP1, SFRP2, SFRP4, and SFRP5 genes may be involved in the morbidity of patients with CCRCC. SFRP 1 and SFRP5 genes may be involved in the development, infiltration, and transfer of CCRCC. SFRP4 gene may be correlated with the malignant behaviors of CCRCC.