胃幽门螺杆菌感染与抑癌基因失活的关系

目的探讨胃癌及癌前病变组织中幽门螺杆菌(H.pylori)感染与抑癌基因失活间的相互关系.方法运用DNA-PCR技术检测H.Pylori感染,采用PCR-RFLP,PCR-SSCP,RT-PCR及免疫组化技术分析182例胃癌及癌前病变及正常胃粘膜中抑癌基因APC,MCC,DCC,YNZ22及p53基因的杂合缺失、突变、mRNA及蛋白异常表达.结果胃癌及癌前病变组织中H.pylori的感染率(IM61.7%,Dys 63.3%,GC 42.3%)显著高于正常胃粘膜(17.5%,P＜0.05).但胃癌及癌前病变间H.pylori感染率无显著差别(P＞0.05),胃肠两型胃癌中H.pylori感染率分别为47.1%及42.2%,两者无显著差别(P＞0.05).胃癌及癌前病变组织中存在多种抑癌基因失活.H.pylori感染与癌前病变-肠化生中APC基因异常蛋白表达有关(Hp+43.2%vsHp-13.0%,P＜0.05).胃癌组织H.pylori感染阳性组中APC基因突变(50.0%)及蛋白表达(63.6%)、p53基因蛋白表达率(59.1%)显著高于阴性组(vs16.7%,P＜0.05;vs30.0%,P＜0.01;vs20.0%,P＜0.01).结论幽门螺杆菌感染及多种抑癌基因失活可能与胃癌的发生发展相关,H.pylori感染与APC,p53基因失活可能相关.

A study on relationship between infection of Helicobacter pylori and inactivation of antioncogenes in cancer and pre-cancerous lesion

AIM To explore the relationship between the infection of Helicobacter pylori(H.pylori)and the inactivation of antioncogenes in tissue of gastric cancer(GC)and pre- cancerous lesions. METHODS Infection of H.pylori was detected with technique of DNA-PCR.Inactivation of antioncogenes of APC,MCC,DCC,YNZ22 and p53 was investigated by PCR- SSCP,PCR-RFLP,RT-PCR and immunohistochemical technique in GC and precancerous lesions. RESULTS The frequence of H.pylori infection in GC and precancerous lesions(IM 61.7%,Dys 63.3%,GC 42.3%) was significantly higher than that of control normal gastric mucosa(17.5%,P<0.05).There was no notable difference in H.pylori infection between GC and precancerous lesions, neither between gastric type and intestinal type of GC (47.1% vs 42.2%,P>0.05).Inactivation(mutation,loss of heterozygosity or expression and protein expression)of multiple antioncogenes was detected in GC and precancerous lesions.There was significant relationship between H.pylori infection and expression of APC gene protein in precancerous lesions(IM Hp~ 43.2% vs Hp~- 13.0%,P<0.05).The rate of APC gene mutation and protein expression and p53 protein expression was significantly higher in H.pylori infection positive group(50.0%,63.6%,59.1%)than that of negative group in GC(vs 16.7%,P<0.05;vs 30.0%,P<0.01;vs 20.0%,P<0.01). CONCLUSION Inactivation of multiple antioncogenes and H.pylori infection may be involved in the development and progress of GC,and H.pylori infection may be associated with the inactivation of APC and p53 genes.