核因子κB p65及靶基因在CagAHp胃癌及癌前病变中的表达研究

Expression of NFκB p65 and its target genes in gastric cancer and precancerous lesions

目的 检测核因子κappaBp6 5 (NFκBp6 5 )及靶基因在幽门螺杆菌 (Hp)感染的肠上皮化生 (IM)、不典型增生 (Dys)、胃癌 (GC)组织中的表达 ,探讨表达细胞毒素相关抗原A的幽门螺杆菌(CagA+ Hp)致胃癌的分子生物学机制。方法 采用ELISA方法检测患者血液中的CagA抗体 ;以快速尿素酶试验和Warthinstarry法检测组织中的Hp ;以免疫组织化学方法检测 12 2例肠上皮化生、10 4例不典型增生及 6 3例胃癌组织中的NFκBp6 5及其靶基因c myc、CyclinD1和bcl xl的表达。结果 IMⅠ和IMⅡ、IMⅢ、DysⅠ、DysⅡ和DysⅢ以及GC组织中 ,NFκBp6 5阳性表达率在CagA阳性组较CagA阴性组高 ,差异有显著性。IMⅢ、DysⅡ和DysⅢ组织中 ,c myc、CyclinD1和bcl xl在CagA阳性组表达率较CagA阴性组高 ,差异有显著性。NFκBp6 5在IMⅢ、DysⅡ和DysⅢ组织中 ,阳性表达率与靶基因阳性表达相一致。CagA+ Hp感染的胃癌组织中 ,NFκBp6 5、c myc、CyclinD1和bcl xl阳性表达率在肠型胃癌中高于弥漫型胃癌 ,差异有显著性。结论 弥漫型胃癌与肠型胃癌的发生机制不同。CagA+ Hp感染与肠型胃癌发生有关 ;CagA+ Hp感染后 ,NFκBp6 5上调c myc、CyclinD1和bcl xl在肠上皮化生及不典型增生组织中的表达 ,促进肠型胃癌发生。通过抑制NFκBp6 5的活?

Objective To study the expression of NFκB p65 and its target genes in intestinal metaplasia (IM), dysplasia (Dys), gastric cancer (GC) infected with Helicobacter pylori (Hp) and explore the mechanism of infection by cytotoxin-associated antigen A expressing Hp (CagA^+Hp) in the development of gastric cancer. Methods CagA antibody in blood sample of 289 patients was determined by ELISA. Hp was detected by rapid urease test and Warthin starry staining. Expression of NFκB p65 and its target genes in IM, Dys and GC was examined by immunohistochemistry. Results In IM Ⅰ～Ⅱ, IMⅢ, DysⅠ, DysⅡ～Ⅲ and GC, the expression of NFκB p65 was significantly higher in patients with CagA^+Hp infection than those without CagA Hp infection. In IMⅢ and DysⅡ～Ⅲ, the expression of NFκB p65, c-myc, CyclinD_1 and bcl-xl was significantly higher in patients with CagA Hp infection than those without CagA Hp infection. In gastric cancer infected with CagA^+Hp, the expression of NFκB p65, c-myc, CyclinD_1 and bcl-xl was significantly higher in intestinal type than in diffuse type. Conclusion There are different mechanisms in intestinal type and diffuse type in the development of gastric cancer. The occurrence of intestinal type gastric cancer is associated with CagA^+Hp infection which by NFκB p65 upregulating the expression of c-myc, CyclinD_1, bcl-xl in patients with IMⅢ, DysⅡ～Ⅲ. It may be an effective method to prevent gastric cancer by inhibiting NFκB p65.