ELP2/STAT3/SETD2基因组拷贝数变异与胃癌化疗反应的相关性研究  

Study on the correlation between ELP2/STAT3/SETD2 genomic copy number variation and chemotherapy response in gastric carcinoma

作　　者：刘琼茹[1] 黄秀芳[1] 梁津杰 方晓华[1] 蔡育波 杨文丽[1] 黄辉 陈艳虹 陈仙兰 张鑫[1,2] 林碧华 LIU Qiongru;HUANG Xiufang;LIANG Jinjie;FANG Xiaohua;CAI Yubo;YANG Wenli;HUANG Hui;CHEN Yanhong;CHEN Xianlan;ZHANG Xin;LIN Bihua(Department of Pathology,Jiangmen Central Hospital,Jiangmen,Guangdong 529030,China;Key Laboratory for Medical Molecular Diagnostics of Guangdong Province,Guangdong MedicalUniversity,Dongguan,Guangdong 523808,China;Department of Biochemistry and Molecular Biology,Guangdong Medical University,Dongguan,Guangdong 523808,China)

机构地区：[1]广东省江门市中心医院病理科,529030 [2]广东医科大学广东省医学分子诊断重点实验室,广东东莞523808 [3]广东医科大学生物化学与分子生物学教研室,广东东莞523808

出　　处：《重庆医学》2019年第9期1504-1508,共5页Chongqing medicine

基　　金：国家自然科学基金资助项目(81272434;81802918);广东省自然科学基金资助项目(2018A030310007);广东省医学科研基金资助项目(A2016395;A2017103);广东省中医药局科研项目(20172085;20181273);广东省东莞市医疗卫生科技计划项目(2016105101292);广东省江门市科技计划项目[江科(2013)81-30;江科(2018)123-115]

摘　　要：目的探讨与胃癌化疗反应相关基因的拷贝数变异情况。方法从癌症基因组图谱计划数据库(TCGA)中,获得胃癌的全基因组拷贝数变异数据和临床用药数据。利用GISTIC 2.0软件分析肿瘤组织中基因组拷贝数变异情况,并分析热点基因的拷贝数变异情况与患者临床治疗反应间的相关性。收集整理2008年1月到2013年12月在江门市中心医院就诊的胃癌患者信息,利用荧光定量PCR检测肿瘤组织中乙酰基转移酶延伸因子复合物亚基2(ELP2)、信号转导及转录激活因子3(STAT3)和组蛋白甲基转移酶SETD2编码基因的拷贝数变异,并分析其与患者临床治疗反应间的相关性。结果截止2018年5月31日,TCGA数据库中有135位胃癌患者记录了治疗反应情况,分析发现,ELP2和STAT3基因的扩增及SETD2基因的缺失与患者发生化疗抵抗相关(P<0.05),且预示着患者更短的总生存时间及无进展生存时间。在该院的64例胃癌患者中,验证到ELP2/STAT3/SETD2基因组拷贝数变异与患者发生化疗抵抗相关(P<0.05)。结论胃癌组织中ELP2/STAT3/SETD2基因组拷贝数变异可能与患者化疗反应相关,可预判患者的化疗反应情况。Objective To investigate the copy number variation(CNV)involved in the chemotherapy response in gastric carcinoma.Methods Patients′information and CNV data for gastric carcinoma were download from The Cancer Genome Atlas(TCGA).The CNV significant analysis was used by GISTIC 2.0 program.The correlation between CNV of hot genes and chemotherapy response of patients was analyzed.Collected the information of patients with gastric carcinoma from January 2008 to December 2013 in Jiangmen Central Hospital.The CNV of elongator acetyltransferase complex subunit 2(ELP2),gain of signal transducer and activator of transcription 3(STAT3),or deletion of Histone-Lysine N-Methyltransferase SETD2 encoding gene was analysis by real-time PCR.The correlation with chemotherapy response was analyzed by GraphPad Prism 5.0 program.Results Up to May 31,2018,there were 135 patients′clinical response in TCGA database.Analysis showed the amplification of ELP2 and STAT3 genes,the deletion of SETD2 gene was associated with the occurrence of chemotherapy resistance in patients(P<0.05).It also predicted that the CNV of ELP2/STAT3/SETD2 correlated with overall survival and progression survival in patients with gastric carcinoma from TCGA.There were 64 patients′chemotherapy response in Jiangmen Central Hospital,and the CNV of ELP2/STAT3/SETD2 correlated with chemotherapy resistant in patients(P<0.05).Conclusion Amplification of ELP2 and STAT3 or deletion of SETD2 might be involved in the chemotherapy response of gastric carcinoma,which predict the chemotherapy response of patients.

关 键 词：胃肿瘤 基因 拷贝数变异 乙酰基转移酶延伸因子复合物亚基2 信号转导及转录激活因子3 组蛋白甲基转移酶SETD2 

分 类 号：R735.2[医药卫生—肿瘤]