Li Wei, Xia Ding, Wang Yuanbao, Li Yi, Xue Yanli, Wu Xin, Ye Zhangqun
Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Department of Urology, the People's Hospital of Yunnan Province, Kunming, 650032, China.
J Huazhong Univ Sci Technolog Med Sci. 2011 Dec;31(6):794-798. doi: 10.1007/s11596-011-0679-6. Epub 2011 Dec 16.
This study examined the promoter methylation of APO-1/CD95 (Fas) gene in bladder urothelial carcinoma and analyzed the relationship between the Fas promoter methylation and the biological behavior of bladder cancer. Promoter methylation of Fas gene was detected by methylation-specific PCR (MSP) in 4 bladder cancer cell lines, 50 human bladder urothelial carcinoma samples and l0 normal bladder tissue samples. Correlation of the aberrant methylation of Fas promoter with the clinicopathological parameters was statistically analyzed. The results showed that Fas was down-regulated at both mRNA and protein level in bladder cancer cell lines and tissue samples of bladder urothelial carcinoma. The positive rate of Fas protein expression in bladder urothelial carcinoma was 34.0% (17/50), significantly lower than that in normal bladder tissues (70.0%, 7/10) (P<0.01). Fas promoter methylation was detected, and the positive rate of Fas promoter methylation in bladder urothelial carcinoma was 42.0% (21/50), which was obviously higher than that in normal bladder tissues (0.0%, 0/10) (P<0.01). The aberrant methylation of Fas promoter was reversely correlated with Fas protein expression (P<0.05). Furthermore, the positive rates of Fas promoter methylation in high-grade and low-grade bladder urothelial carcinoma were 73.3% (11/15) and 34.2% (12/35), respectively, with significant difference shown (P<0.05). No statistical significance was found in the Fas promoter methylation among different clinical stages of bladder cancer. It was concluded that Fas promoter hypermethylation plays an important role in the pathogenesis of bladder urothelial carcinoma and may serve as a prognostic indicator of bladder urothelial carcinoma.
本研究检测了膀胱尿路上皮癌中APO-1/CD95（Fas）基因的启动子甲基化情况，并分析了Fas启动子甲基化与膀胱癌生物学行为之间的关系。采用甲基化特异性PCR（MSP）法检测4株膀胱癌细胞系、50例人膀胱尿路上皮癌组织样本及10例正常膀胱组织样本中Fas基因的启动子甲基化情况。对Fas启动子异常甲基化与临床病理参数的相关性进行统计学分析。结果显示，在膀胱癌细胞系及膀胱尿路上皮癌组织样本中，Fas在mRNA和蛋白水平均呈下调状态。膀胱尿路上皮癌中Fas蛋白表达阳性率为34.0%（17/50），显著低于正常膀胱组织（70.0%，7/10）（P<0.01）。检测到Fas启动子甲基化，膀胱尿路上皮癌中Fas启动子甲基化阳性率为42.0%（21/50），明显高于正常膀胱组织（0.0%，0/10）（P<0.01）。Fas启动子异常甲基化与Fas蛋白表达呈负相关（P<0.05）。此外，高级别和低级别膀胱尿路上皮癌中Fas启动子甲基化阳性率分别为73.3%（11/15）和34.2%（12/35），差异有统计学意义（P<0.05）。在膀胱癌不同临床分期中，Fas启动子甲基化无统计学差异。结论：Fas启动子高甲基化在膀胱尿路上皮癌的发病机制中起重要作用，可能作为膀胱尿路上皮癌的预后指标。
