Quantitative analysis of promoter methylation of the EDNRB gene in gastric cancer

Quantitative analysis of promoter methylation of the EDNRB gene in gastric cancer
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胃癌EDNRB基因启动子甲基化的定量分析

DOI:
10.1007/s12032-010-9805-8
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发表时间:
2012-03-01
期刊:
影响因子:
3.4
通讯作者:
Wang, Guobin
Wang, Guobin
中科院分区:
医学4区
文献类型:
--
作者:
Tao, Kaixiong;Wu, Chuanqing;Wang, Guobin

文献摘要

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内皮素受体B(EDNRB)基因启动子区的高甲基化已被证明在几种人类肿瘤。然而,其在胃癌形成中的作用仍不清楚。本研究采用焦磷酸测序法对96例胃癌患者的配对组织及癌旁正常组织中EDNRB基因的甲基化状态进行了定量检测。结果显示,胃癌组织中EDNRB基因启动子甲基化率(50.42 ± 9.03%)显著高于癌旁正常组织(6.47 ± 2.98%)(P< 0.01)。在96例肿瘤组织中,EDNRB基因启动子区甲基化与肿瘤浸润(T1:47.4 ± 7.31%T2:48.2 ± 9.17%T3:52.9 ± 6.48%T4:53.2 ± 10.45%)、淋巴结转移(N 0:45.4 ± 6.99%N1:49.0 ± 9.10%N2:52.0 ± 8.40%N3:53.7 ± 9.92%)和远处转移(M0:48.9 ± 6.99%M1:53.9 ± 11.98%)相关(P< 0.05),但与其他临床病理特征无关。此外,用去甲基化剂处理人胃癌细胞系SGC-7901可以恢复EDNRB的表达。本研究结果提示EDNRB基因启动子区甲基化在胃癌中存在,可能在胃癌的发病机制中起一定作用。EDNRB基因甲基化与胃癌的浸润和转移密切相关,可能是胃癌进展的重要因素。
Hypermethylation has been shown in the promoter region of the endothelin receptor B (EDNRB) gene in several human tumors. However, its role in gastric cancer formation is still unclear. In this study, the methylation status of the EDNRB gene in paired gastric cancer tissues and adjacent normal tissues from 96 patients was detected quantitatively using pyrosequencing. The results showed the methylation of promoter of EDNRB gene in gastric cancer (50.42 ± 9.03%) was significantly higher than in adjacent normal tissues (6.47 ± 2.98%) (P< 0.01). Among 96 tumor tissues, promoter hypermethylation of the EDNRB gene was correlated with tumor infiltration (T1: 47.4 ± 7.31% T2:48.2 ± 9.17% T3:52.9 ± 6.48% T4:53.2 ± 10.45%), lymph node metastasis (N0:45.4 ± 6.99% N1:49.0 ± 9.10% N2:52.0 ± 8.40% N3:53.7 ± 9.92%), and distant metastasis (M0:48.9 ± 6.99% M1:53.9 ± 11.98%) (P< 0.05), but it was not associated with other clinicopathological characteristics. In addition, the treatment of the human gastric cancer cell line, SGC-7901, with demethylation agent can restore the expression of EDNRB. Our results suggest that promoter hypermethylation of EDNRB gene is highly prevalent in gastric cancer, which may play a role in the pathogenesis of gastric cancer. Futhermore, hypermethylation of EDNRB gene was remarkably related to infiltration and metastasis of gastric cancer and may attribute to the tumor progression.