幽门螺杆菌感染和端粒酶活性以及c-myc、p16基因的表达在胃黏膜癌变中的相关性研究

Helicobacter pylori Infection, Telomerase Activity and the Expression of c-myc and p16 Genes in the Process of Gastric Tumorigenesis

幽门螺杆菌(H.pylori)是胃癌的主要致病因子,H.pylori、端粒酶和肿瘤相关基因的关系在胃黏膜癌变发生过程中研究很少。目的:观察H.pylori感染和端粒酶活性以及c-myc、p16基因在胃癌中的关系。方法:通过胃镜活检和外科手术获取171例胃组织标本,快速尿素酶试验和H.pylori培养确定有无H.pylori感染;酶联免疫法检测H.pylori感染患者的血清CagA-IgG水平;聚合酶链反应.酶联免疫吸附测定(PCR-ELISA)法检测端粒酶活性;免疫组化法检测c-myc、p16基因的表达。结果:胃癌(GC)组端粒酶表达率显著高于其他各组(P<0.01);慢性萎缩性胃炎(CAG)伴中、重度肠化(IM)组端粒酶和c-myc表达率显著高于CAG伴轻度IM组(P<0.05);而慢性浅表性胃炎(CSG)和CAG伴轻度IM组p16表达率显著高于CAG伴中、重度IM、异型增生(Dys)和GC组(P<0.05)。在CAG伴轻、中、重度IM组中,H.pylori阳性组端粒酶活性比阴性组高:无论有无H.pylori感染,胃癌组端粒酶活性都非常高。在CAG伴中、重度IM、Dys和GC组中,H.pylori阳性亚组c-myc表达显著高于阴性亚组(P<0.01),而在ECAG伴中、重度IM和Dys组中,H.pylori阳性亚组p16基因表达显著低于阴性亚组(P<0.01)。结论:H pylori感染很可能主要通过c-myc基因的激活和p16基因的失活以及其他基因的变化来诱导CAG伴中。

Background: Helicobacter pylori (H. pylori) is a main etiological factor of gastric cancer, but there are only few studies on H. pylori infection, telomerase and cancer related genes in the process of gastric carcinogenesis. Aims: To explore the relationship between H. pylori infection, telomerase activity, expression of c-myc and p16 genes in gastric cancer. Methods: One hundred and seventy-one gastric biopsy specimens were taken at endoscopy and surgery. H. pylori was detected by rapid urease test and culture. CagA-IgG was determined by enzyme immunoassay and telomerase activity was assayed by polymerase chain reaction (PCR)-enzyme-linked immunosorbent assay (ELISA). The expression of c-myc and p16 genes was detected by immunohistochemical technique. Results: Telomerase activity was the highest in gastric cancer (GC) as compared with other groups (P<0.01). The telomerase activity and the expression of c-myc in chronic atrophic gastritis (CAG) with moderate or severe intestinal maetaplasia (IM) were significantly higher than those in CAG with mild IM (P<0.05), whereas the expression of p16 in chronic superficial gastritis (CSG) and CAG with mild IM was significantly higher than that in other groups, such as CAG with moderate or severe IM, dysplasia and GC (P<0.05). It was found that in case of H. pylori infection the telomerase activity was higher in CAG with mild IM and moderate or severe IM than those without the H. pylori infection. The telomerase activity was very high in gastric cancer with or without H. pylori infection. The expression of c-myc in H. pylori positive subgroup was significantly higher than that in H. pylori negative subgroup in CAG with moderate or severe IM, dysplasia and gastric cancer (P<0.01), while the expression of p16 in H. pylori positive subgroup was significantly lower than that in H. pylori negative subgroup in CAG with moderate or severe IM and dysplasia (P< 0.01). Conclusions: H. pylori may initiate the development of gastric cancer by activating c-myc and inactivating p16 genes through telomerase activity in CAG with moderate or severe IM, which may probably be one of the mechanisms that lead to gastric cancer.