胃癌组织中miR-218和凋亡相关蛋白Bcl-2、Bax、xIAP、Survivin mRNA的表达观察

Expression of miR-218 and apoptosis-related proteins Bcl-2,Bax,xIAP and Survivin mRNA in gastric cancer

目的观察胃癌组织中微小RNA-218(miR-218)和凋亡相关蛋白Bcl-2、Bax、x IAP、Survivin mRNA的表达变化,并探讨其意义。方法胃癌患者80例,手术过程中留取癌组织及癌旁组织,采用实时定量PCR法对胃癌组织及癌旁组织中的miR-218和凋亡相关蛋白Bcl-2、Bax、x IAP、Survivin mRNA进行检测,分析其相关性。以胃癌组织中miR-218相对表达强度的平均值为界,将胃癌患者分为miR-218高表达组与miR-218低表达组,对比分析其临床病理参数及预后。结果胃癌组织中miR-218及Bcl-2、Bax、x IAP、Survivin mRNA的相对表达强度分别为0. 3077±0. 118 1、0. 817 7±0. 272 6、0. 248 1±0. 110 8、0. 599 5±0. 261 3、0. 820 9±0. 342 6,癌旁组织中分别为0. 565 9±0. 226 0、0. 277 4±0. 116 7、0. 444 4±0. 201 9、0. 298 7±0. 147 8、0. 247 0±0. 112 2,两种组织各指标相比,P均<0. 01。胃癌组织中miR-218与Bcl-2 mRNA的表达呈负相关(r=-0. 341,P <0. 01),miR-218与Bax mRNA的表达呈正相关(r=0. 522,P <0. 01),Bcl-2 mRNA与Bax mRNA的表达呈负相关(r=-0. 439,P <0. 01),Bcl-2 mRNA与Survivin mRNA的表达呈正相关(r=0. 235,P <0. 01)。80例胃癌患者中,胃癌组织中miR-218高表达组42例、低表达组38例; miR-218高表达组中TNM分期Ⅰ期+Ⅱ期21例、Ⅲ期+Ⅳ期21例,miR-218低表达组中Ⅰ期+Ⅱ期9例、Ⅲ期+Ⅳ期29例,两组相比,P <0. 05; miR-218高表达组中淋巴结转移者29例,miR-218低表达组中淋巴结转移者34例,两组相比,P <0. 05;胃癌组织中miR-218高表达组、低表达组的5年生存率分别为66. 67%、28. 95%,两组相比,χ2=9. 789,P <0. 01。结论胃癌组织中miR-218呈低表达; miR-218可能通过参与凋亡相关蛋白Bcl-2、Bax、Survivin基因表达的相互调节而参与肿瘤细胞凋亡过程;胃癌组织中miR-218低表达预示肿瘤处于较高临床分期、淋巴结转移可能性较大,患者预后较差。

Objective To observe the expression of microRNA 218(miR-218)and apoptosis-related genes Bcl-2,Bax,xIAP,and Survivin mRNA in the gastric cancer tissues.Methods Eighty gastric cancer patients were enrolled in this study,and gastric cancer tissues,cancer-adjacent normal tissues were collected during operations,then real-time PCR was applied to test miR-128 and apoptosis-related genes Bcl-2,Bax,xIAP,and Survivin mRNA.Meanwhile,the correlation among these indexes was investigate.We used the mean value of the relative expression intensity of miR-218 in gastric cancer tissues as the boundary,and the gastric cancer patients were divided into the high miR-218 group and low miR-218 group,and then clinicopathological parameters and prognosis were also investigated.Results The levels of miR-218 and Bcl-2,Bax,xIAP,Survivin mRNA in the gastric cancer tissues were 0.307 7±0.118 1,0.817 7±0.272 6,0.248 1±0.110 8,0.5995±0.2613,and 0.820 9±0.342 6,respectively,and these indexes in the cancer-adjacent normal tissues were 0.5659±0.226 0,0.277 4±0.116 7,0.444 4±0.201 9,0.298 7±0.147 8,and 0.247 0±0.112 2,respectively,with statistical difference(all P<0.01).There was a negative correlation between miR-218 and Bcl-2 mRNA expression in the gastric cancer tissues(r=-0.341,P<0.01),and miR-218 was positively correlated with Bax mRNA expression(r=0.522,P<0.01).Bcl-2 mRNA was negatively correlated with the expression of Bax mRNA(r=-0.439,P<0.01),and Bcl-2 mRNA was positively correlated with the expression of Survivin mRNA(r=0.235,P<0.01).In 80 patients,42 cases were in the high miR-218 group,and 38 cases were in the low miR-218 group;there were 21 cases of stageⅠ+Ⅱand 21 cases of stageⅢ+Ⅳin the high miR-218 group,and there were 9 cases of stage I+II and 29 cases of stageⅢ+Ⅳin the low miR-218 group,with significant difference(P<0.05).Twenty-nine cases with lymphatic metastasis were verified in the high miR-218 group,and 34 cases with lymphatic metastasis were verified in the low miR-218 group,with significant difference(P<0.05).The 5-year survival rates in the high miR-218 group and low miR-218 group were 66.67%and 28.95%,respectively,with significant difference(χ^2=9.789,P<0.01).Conclusion The miR-218 in gastric cancer is lowly expressed,miR-218 may be invovled in progression of gastric cancer by regulating Bcl-2,Bax,and survivin genes,and the low expression of miR-218 in gastric cancer tissues indicates that the tumor is in a high clinical stage,the possibility of lymph node metastasis is high,and the prognosis is poor.