Wang Zhenkai, Ye Yaqing, Liu Dan, Yang Xiaoqian, Wang Fangyu
Endoscopy Center, Nanjing hospital of Traditional Chinese Medicine, Nanjing, Jiangsu Province.
Fujian Health Vocational and Technical College, Fuzhou, Fujjian Province.
Medicine (Baltimore). 2018 Dec;97(52):e13734. doi: 10.1097/MD.0000000000013734.
Wnt antagonist genes hypermethylation has been found in several tumors. Accordingly, the events that occur during the progression of adenoma to carcinoma have been characterized and include activation of the Wnt-pathway. Further, gastric adenoma (GA) is a premalignant lesion of gastric adenocarcinoma (GAC). In this paper, we focused our interesting on Wnt signaling path function in the pathogenesis of GAC.We compared the differences between low grade adenoma (LGA), high grade adenoma (HGA), GACs and corresponding normal gastric tissue (NGT). Specific indexes include the pathological characteristics of gastric neoplasia, Helicobacter pylori infection, β-catenin mutation status, and methylation status of Wnt antagonist genes.There was significant difference of β-catenin expression in patient with NGT, LGA, HGA, and GAC, the results respectively were 4.2%, 41.7%, 83.3%, and 91.7%. Only 1 GACs was detected exon 3 of β-catenin mutation. Wnt antagonist genes mRNA expression levels, such as APC, sFRP-1, Wif-1, and Dkk-1, were significantly reduced in GAC. Promoter methylation levels of the 4 genes were significantly elevated in GAC and HGA compared to NGT and LGA. However, there was no significant difference between HGAs and GACs. The β-catenin abnormal expression was correlated with hypermethylation of these 4 genes. Multiple gene concurrent methylation phenomenon was increased from NGTs to GACs; the amount of methylation genes in GACs and HGAs was more than NGTs and LGAs. The more methylation of the above-mentioned genes, the more severity of local inflammation. The infection rate of H pylori was significantly higher in patient with HGA (66.7%, 16/24) and GAC (58.5%, 14/24) than in LGAs (16.7%,4/24) (PHGA-LGA = .024, PGAC-LGA = .032). In addition, the present of H pylori also correlated with the β-catenin abnormal expression and the hypermethylation status of Wnt antagonist genes (P < .001). But other parameters in adenoma cases had no significantly related with infection of H pylori.Hypermethylation of Wnt antagonist genes may have a tight relationship with gastric tumorigenesis. And these genes may increase the incidence of GAC. Additionally, H pylori may have promotion function in GA formation.
在几种肿瘤中已发现Wnt拮抗剂基因的高甲基化。因此，腺瘤向癌进展过程中发生的事件已得到表征，包括Wnt信号通路的激活。此外，胃腺瘤（GA）是胃腺癌（GAC）的癌前病变。在本文中，我们重点研究了Wnt信号通路在GAC发病机制中的作用。我们比较了低级别腺瘤（LGA）、高级别腺瘤（HGA）、GAC和相应正常胃组织（NGT）之间的差异。具体指标包括胃肿瘤的病理特征、幽门螺杆菌感染、β-连环蛋白突变状态以及Wnt拮抗剂基因的甲基化状态。NGT、LGA、HGA和GAC患者的β-连环蛋白表达存在显著差异，结果分别为4.2%、41.7%、83.3%和91.7%。仅在1例GAC中检测到β-连环蛋白第3外显子突变。GAC中Wnt拮抗剂基因mRNA表达水平，如APC、sFRP-1、Wif-1和Dkk-1，显著降低。与NGT和LGA相比，GAC和HGA中这4个基因的启动子甲基化水平显著升高。然而，HGA和GAC之间没有显著差异。β-连环蛋白异常表达与这4个基因的高甲基化相关。从NGT到GAC，多基因同时甲基化现象增加；GAC和HGA中的甲基化基因数量多于NGT和LGA。上述基因甲基化越多，局部炎症越严重。HGA患者（66.7%，16/24）和GAC患者（58.5%，14/24）的幽门螺杆菌感染率显著高于LGA患者（16.7%，4/24）（PHGA-LGA = 0.024，PGAC-LGA = 0.032）。此外，幽门螺杆菌的存在也与β-连环蛋白异常表达和Wnt拮抗剂基因的高甲基化状态相关（P < 0.001）。但腺瘤病例中的其他参数与幽门螺杆菌感染无显著相关性。Wnt拮抗剂基因的高甲基化可能与胃肿瘤发生密切相关。并且这些基因可能增加GAC的发病率。此外，幽门螺杆菌可能在GA形成中具有促进作用。
