Department of Laparoscopic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei 430022, People's Republic of China.
Med Oncol. 2012 Mar;29(1):107-12. doi: 10.1007/s12032-010-9805-8. Epub 2011 Jan 25.
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.
在多种人类肿瘤中,内皮素受体 B(EDNRB)基因的启动子区域存在超甲基化。然而,其在胃癌形成中的作用尚不清楚。在这项研究中,使用焦磷酸测序法定量检测了 96 例患者配对的胃癌组织和相邻正常组织中 EDNRB 基因的甲基化状态。结果显示,胃癌中 EDNRB 基因启动子的甲基化(50.42 ± 9.03%)明显高于相邻正常组织(6.47 ± 2.98%)(P < 0.01)。在 96 例肿瘤组织中,EDNRB 基因启动子的高甲基化与肿瘤浸润(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(N0:45.4 ± 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%)有关(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。我们的结果表明,EDNRB 基因启动子的高甲基化在胃癌中很常见,可能在胃癌的发病机制中起作用。此外,EDNRB 基因的高甲基化与胃癌的浸润和转移显著相关,可能导致肿瘤的进展。