Inactivation of COX-2, HMLH1 and CDKN2A Gene by Promoter Methylation in Gastric Cancer: Relationship with Histological Subtype, Tumor Location and Helicobacter pylori Genotype
Inactivation of COX-2, HMLH1 and CDKN2A Gene by Promoter Methylation in Gastric Cancer: Relationship with Histological Subtype, Tumor Location and Helicobacter pylori Genotype
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DOI：
10.1159/000329475
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发表时间：
2011-08
期刊：
影响因子：
5
通讯作者：
M. Alves;A. C. Ferrasi;Valeska Portela Lima;M. P. Ferreira;Maria Inês de Moura Campos Pardini;S. Rabenhorst
中科院分区：
文献类型：
--
作者：
M. Alves;A. C. Ferrasi;Valeska Portela Lima;M. P. Ferreira;Maria Inês de Moura Campos Pardini;S. Rabenhorst
目的：本研究旨在探讨胃癌组织中考克斯-2、HMLH 1和CDKN 2A基因启动子甲基化失活及其与幽门螺杆菌感染的关系。方法：从76 H. pylori阳性的胃肿瘤标本可通过甲基化特异性PCR和H. pylori分型。免疫组化法检测考克斯-2、p16 INK 4A和HMLH 1的表达。结果：发现这些标记物的表达与其基因启动子甲基化的存在之间存在强负相关。在贲门癌中，p16 INK 4A的阴性是一个重要的发现。另一方面，在非贲门部肿瘤中，组织学亚型具有不同的基因表达模式。在肠亚型中，一个显著的发现是HMLH 1甲基化失活，而在弥漫亚型中，CDKN 2A甲基化失活是显著的发现。考克斯-2和HMLH 1基因甲基化的肿瘤与H. pylori vacA s1（p分别为0.025和0.047），非甲基化肿瘤与基因flaA的存在相关。结论：这些数据表明，这些基因的甲基化失活发生不同的途径，根据组织学亚型和肿瘤的位置，并依赖于H。pylori基因型
Objective: We aimed to evaluate the inactivation of COX-2, HMLH1 and CDKN2A by promoter methylation and its relationship with the infection by different Helicobacter pylori strains in gastric cancer. Methods: DNA extracted from 76 H. pylori-positive gastric tumor samples was available for promoter methylation identification by methylation-specific PCR and H. pylori subtyping by PCR. Immunohistochemistry was used to determine COX-2, p16INK4A and HMLH1 expression. Results: A strong negative correlation was found between the expression of these markers and the presence of promoter methylation in their genes. Among cardia tumors, negativity of p16INK4A was a significant finding. On the other hand, in noncardia tumors, the histological subtypes had different gene expression patterns. In the intestinal subtype, a significant finding was HMLH1 inactivation by methylation, while in the diffuse subtype, CDKN2A inactivation by methylation was the significant finding. Tumors with methylated COX-2 and HMLH1 genes were associated with H. pylori vacA s1 (p = 0.025 and 0.047, respectively), and the nonmethylated tumors were associated with the presence of the gene flaA. Conclusions: These data suggest that the inactivation of these genes by methylation occurs by distinct pathways according to the histological subtype and tumor location and depends on the H. pylori genotype.