Unidade Integrada de Farmacologia e Gastroenterologia, Universidade São Francisco, Av. São Francisco de Assis, 218. Jd. São José, Bragança Paulista, SP, Brazil.
Dig Dis Sci. 2013 Oct;58(10):2850-7. doi: 10.1007/s10620-013-2742-6. Epub 2013 Jun 14.
Helicobacter pylori infection is usually acquired in childhood and persists into adulthood if untreated. The bacterium induces a chronic inflammatory response, which is associated with epigenetic alterations in oncogenes, tumor-suppressor genes, cell-cycle regulators, and cell-adhesion molecules.
The aim of this study was to analyze the effect of H. pylori infection on the methylation status of Thrombospondin-1 (THBS1), Hypermethylated in cancer 1 (HIC1) and Gata binding protein-4 (GATA-4) in gastric biopsy samples from children and adults infected or uninfected with the bacterium and in samples obtained from gastric cancer patients.
The methylation pattern was analyzed with methylation-specific PCR.
Our results showed that H. pylori infection was associated with methylation of the promoter regions of the THBS1 and GATA-4 genes in pediatric and adult samples (p < 0.01). HIC1 showed the lowest level of methylation, which was not an early event during gastric carcinogenesis.
The results from this study indicate that methylation of THBS1 and GATA-4 occurs in the early stages of chronic gastritis and gastric cancer in association with H. pylori infection; however, in gastric cancer samples, other mechanisms cooperate with the down-regulation of these genes. Methylation of HIC1 may not be the principal mechanism implicated in its down-regulation in gastric cancer samples.
幽门螺杆菌感染通常在儿童时期获得，如果未经治疗，会持续到成年。该细菌会引起慢性炎症反应，与癌基因、肿瘤抑制基因、细胞周期调节剂和细胞黏附分子的表观遗传改变有关。
本研究旨在分析幽门螺杆菌感染对儿童和成人感染或未感染细菌的胃活检样本中血栓素-1（THBS1）、癌症中高甲基化 1（HIC1）和 GATA 结合蛋白-4（GATA-4）基因的甲基化状态的影响，以及胃癌患者的样本。
采用甲基化特异性 PCR 分析甲基化模式。
我们的结果表明，幽门螺杆菌感染与儿科和成人样本中 THBS1 和 GATA-4 基因启动子区域的甲基化有关（p < 0.01）。HIC1 显示出最低的甲基化水平，这不是胃癌发生过程中的早期事件。
本研究结果表明，THBS1 和 GATA-4 的甲基化发生在慢性胃炎和与幽门螺杆菌感染相关的胃癌的早期阶段；然而，在胃癌样本中，其他机制与这些基因的下调协同作用。HIC1 的甲基化可能不是其在胃癌样本中下调的主要机制。
