进展期胃癌患者O^6-甲基鸟嘌呤-DNA-甲基转移酶蛋白表达与预后的关系  

The relationships between the expression of MGMT and prognosis in the advanced patients with gastric carcinoma

作　　者：贾存慧[1] 禹立霞[1] 魏嘉[1] 邹征云[1] 钱晓萍[1] 刘宝瑞[1] 

机构地区：[1]南京大学医学院附属鼓楼医院肿瘤中心暨南京大学临床肿瘤学研究所

出　　处：《医学研究生学报》2011年第5期460-466,共7页Journal of Medical Postgraduates

基　　金：江苏省人事厅六大人才高峰(07-B-028);南京市2008年第一批科技发展计划项目(200801078)

摘　　要：目的 O6-甲基鸟嘌呤-DNA-甲基转移酶(O6-methylguanine-DNA-methylt ransferase,MGMT)是修复烷化剂对DNA损伤的关键酶,同时也是烷化剂类抗肿瘤药物耐药的主要因素之一。p53蛋白是p53抑癌基因的蛋白产物,其基因突变与肿瘤的发生、发展密切相关。文中探讨了MGMT蛋白在进展期胃癌患者肿瘤组织中的表达与临床病理参数及预后的关系,以及MGMT蛋白与p53蛋白在进展期胃癌组织中表达的相关性及对预后的影响。方法采用免疫组织化学法检测158例进展期胃癌切除标本中MGMT的表达水平,并分析其与胃癌临床病理特征及联合分析MGMT蛋白表达和临床检测指标p53蛋白表达与患者预后的关系。结果进展期胃癌组织中MGMT蛋白的阳性率为76.58%(121/158)。MGMT蛋白表达情况与患者的肿瘤部位及大小、肿瘤分期、分化程度、神经是否侵犯、脉管是否存在癌栓均无相关性(P>0.05)。Spearman相关系数分析显示MGMT与p53的表达呈负相关:r=-0.2534,P=0.0023。COX回归多因素分析显示MGMT(相对危险度:1.339,P=0.1363)和p53(相对危险度:1.174,P=0.4082)不能作为生存时间的独立预测指标。MGMT(+)、p53(-)组的总生存期显著长于MGMT(+)、p53(-)组,差异有统计学意义(P<0.05)。p53(+)、MGMT低表达组的总生存期要显著高于p53(+)、MGMT高表达组(P<0.05)。结论 MGMT蛋白的表达缺失及p53蛋白的表达增强可能共同参与了胃癌的发展过程,联合分析MGMT和p53蛋白的表达情况对于进展期胃癌患者的预后评估可能具有一定的参考价值;而MGMT蛋白低表达相较高表达时的总生存期略长可能存在其他影响因素。Objective O6-methylguanine-DNA-methyltransferase(MGMT)is the key enzyme to repair the DNA damage caused by alkylating agents damage DNA.It is also one of the reasons of resistence for alkylating agent drugs.p53 protein is the product of p53 gene.p53 gene mutation is related to the development and progression of tumors.Our experiment is to study the expression of MGMT in advanced gastric carcinoma tissues and to investigate the relationship between MGMT protein expression and the clinicopathological features of advanced gastric carcinoma.The study also aimed to explore the correlation of the expressions of MGMT protein and p53 protein,the relationship between their expressions and prognosis in advance gastric carcinoma.Methods We investigated the expression of MGMT in 158 advanced gastric cancer specimens by immunohistochemical assay.The relationship among clinicopathologic features,prognosis and expressions of MGMT protein and p53 protein were studied.Results The positive rates of MGMT protein expression in advanced gastric carcinoma was 76.58 %(121/158).MGMT expressions were not related to histologic classification,infiltrating depth,lymph nodes metastasis,TNM stages,nerve encroachment,cancer embolus of vessel.Spearman analysis indicated that the expressions of MGMT and P53 in the advanced gastric carcinoma were negative related each other(r=-0.2534,P=0.0023).COX multivariate regression analysis revealed that MGMT and p53 protein expression did not impact on OS(hazard ratio:1.339,P=0.1363;hazard ratio:1.174,P=0.4082,respectively).The survival curve showed that the loss and decrease of MGMT protein were correlated with a poor prognosis.Combined evaluation of MGMT and p53 revealed that the survival of patients with positive status for MGMT and negative status for p53 were more beneficial.The survival of p53(+),low MGM expression group were higher than that of p53(+),high MGMT expression group.Conclusion The loss and decrease of MGMT protein expression and the enhancement of p53 protein may be related to the progre

关 键 词：MGMT蛋白 P53蛋白 进展期胃癌 免疫组织化学 

分 类 号：R[医药卫生]