膀胱癌HPSE基因启动子区低甲基化与临床病理特征相关性的研究

Correlation of promoter hypomethylation of HPSE gene in bladder cancer and the clinicopathoIogic characteristics

目的:探讨乙酰肝素酶(HPSE)基因启动子区甲基化与膀胱癌临床病理特征的相关性。方法:运用甲基化特异性聚合酶链反应(MSP)法检测27例膀胱癌标本及15例正常膀胱组织中HPSE基因启动子甲基化状态,并分析HPSE基因甲基化状态与不同临床病理特征的关系。结果:59.26%(16/27)膀胱癌组织HPSE基因启动子区发生低甲基化改变,另外2例甚至为完全去甲基化改变;而仅有3例(20.00%)正常膀胱组织HPSE基因启动子区发生低甲基化,χ2=5.999,P=0.014。在17例伴淋巴结转移的患者中,发生HPSE基因低甲基化改变15例(88.23%),而在10例无淋巴结转移的患者中,发生HPSE基因低甲基化改变1例(10.00%)。HPSE低甲基化阳性率随淋巴转移而增高,χ2=12.887,P=0.004。不同性别、年龄、瘤体大小、病理分级和临床分期与HPSE基因低甲基化无明显相关性,P>0.05。结论:HPSE基因启动子区低甲基化为频发事件,提示与膀胱癌患者的不良预后相关,可作为膀胱癌判断预后的生物学标志。

OBJECTIVE：To study the heparanase（HPSE） gene promoter hypomethylation and its relation with clinical pathology of bladder cancer. METHODS： Methylation specific PCR was used to detect the methylation status of HPSE promoter of bladder cancer tissues of 27 patients. Fifteen normal bladder tissues were also tested as control. RESULTS： The hypomethylation rate of baldder cancer and normal bladder tissue were 59. 26% and 20. 00%, respectively （2 = 5. 999,P= 0. 014）. The hepomethylation rate of patients with lymph node metastasis was 15/17 （88. 23 ~）, and 1/10 （10.00 %） case was detected hepomethylation in the non-lymph node metastasis group. The hypomethyiation rate significantly increased with lymph node metastasis （X^2 = 12. 887, P= 0. 004）. There were no significant associations between the hypomethylation frequencies for HPSE gene and patient gender, age, size of tumor, stages and histologic grades （P〉 0.05）. CONCLUSIONS： HPSE promoter hypomethylation may be a frequent epigenetic event of bladder cancer, and may also involve in tumor progression. The methylation rate of HPSE can be used as a molecular marker to predict the prognosis for bladder cancer.