KEAP1基因突变调控Nrf2-ABCG2信号介导胃癌耐药的研究  

Study on mutation of KEAP1 induced chemoresistance in gastric cancer by Nrf2-ABCG2 signalling

作　　者：王昕海[1] 巴桑 晋美 鄂福胜 李孟军[1] 吴双杰[1] 刘骏[1] 唐一帆[1] 

机构地区：[1]复旦大学附属华山医院普外科,上海200040 [2]西藏自治区日喀则市人民医院普外科,西藏日喀则857000

出　　处：《外科理论与实践》2016年第3期233-237,共5页Journal of Surgery Concepts & Practice

基　　金：上海市卫生计生委基金(201440559)

摘　　要：目的:研究KEAP1基因突变通过Nrf2-ABCG2信号通路介导胃癌耐药的分子机制。方法:PCR测序法检测胃癌病人肿瘤组织中KEAP1基因突变,免疫组织化学分析胃癌组织中Nrf2及ABCG2表达情况。根据是否携带KEAP1突变分为突变组和未突变组,比较组间术后生存期及Nrf2和ABCG2表达量。结果 :126例胃癌病人中检测到15例KEAP1基因突变,突变频率为11.9%。KEAP1基因突变组胃癌病人术后中位生存期为14.0个月,低于KEAP1基因无突变组(40.5个月),其差异有统计学意义(χ2=4.360,P<0.001)。KEAP1基因突变的胃癌病人中,Nrf2及ABCG2蛋白表达量高于KEAP1基因未突变的病人,其差异均有统计学意义(P<0.05)。结论 :KEAP1基因突变通过上调Nrf2及ABCG2的表达,增强胃癌细胞的耐药性。Objective To study on the molecular mechanism of chemoresistance induced by KEAP1 mutation via activation of Nrf2-ABCG2 signalling in gastric cancer. Methods Mutation of KEAP1 and expressions of Nrf2 and ABCG2 in gastric cancer were analyzed using PCR sequencing and immunohistochemistry, respectively. The patients were divided into two groups based on KEAP1 mutation. The expressions of Nrf2 and ABCG2, and postoperative survival were compared between KEAP1 mutation group and non-mutation group. Results Of 126 patients, 15 were found KEAP1 mutation with the mutation rate 11.9%. Median postoperative survival of the patients in KEAP1 mutation group was significantly lower than that in KEAP1 non-mutation group （14.0 months vs 40.5 months） （X2=4.360, P〈0.001）. The expressions of Nrf2 and ABCG2 in KEAP1 mutation group were significantly higher than those in KEAP1 non-mutation group （P〈0.05）. Coadusions KEAP1 mutation might promote chemoresistence of gastric cancer through upregulating the expression of Nrf and ABCG2.

关 键 词：胃癌 KEAP1 基因突变 NRF2 ABCG2 肿瘤耐药 

分 类 号：R735.2[医药卫生—肿瘤]