摘要
目的分析与子宫内膜癌化疗反应相关基因的拷贝数变异情况。方法从肿瘤基因组图谱数据库(TCGA)中,获得子宫内膜癌的全基因组拷贝数变异数据和临床用药数据。分析TCGA数据库中患者的用药信息及药物反应情况,并利用GISTIC2.0软件分析患者肿瘤组织中基因组拷贝数变异情况。利用IGV软件定位拷贝数变异热点区域的关键基因,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。结果截至2017年5月31日,TCGA数据库中有65例子宫内膜癌患者记录了治疗反应情况,其中49例呈完全缓解,为化疗敏感(CS)患者,2例呈部分缓解、2例呈病情稳定及12例呈病情进展,此3类患者合称化疗抵抗(CR)患者。进一步分析发现,22q12.2和Xp11.23区段特异性在CR患者肿瘤组织中扩增,1q44区段是CR患者肿瘤组织特异性缺失区段。其中22q12.2区段的扩增中心是白血病抑制因子(LIF)的编码基因,Xp11.23区段的扩增中心是果蝇Porcupine基因同源基因(PORCN)和依莫帕米结合蛋白(EBP)编码基因,1q44区段的缺失中心是驱动蛋白家族成员26B(KIF26B)的编码基因。此外,LIF的扩增和PORCN/EBP的扩增与患者发生化疗抵抗相关(P<0.05),但是KIF26B的缺失与化疗抵抗不相关(P>0.05)。结论子宫内膜癌组织中22q12.2区段(LIF)和Xp11.23区段(PORCN/EBP)的扩增及1q44区段(KIF26B)的缺失可能与患者化疗的抵抗相关,可以预判患者的化疗反应情况。
OBJECTIVE To investigate the copy number variations（ CNV） involved in the chemotherapy of endometrial cancer.METHODS The patients＇ information and CNV data for endometrial cancer were download from The Cancer Genome Atlas（ TCGA）.The CNV significant analysis was used by GISTIC2. 0 program,and patients＇ drug information was analyzed. The hot pot of CNV in genome location was visualized by IGV program,and the correlated with drug respond was analyzed. RESULTS Up to May 31,2017,there were 65 patients ＇drug information in TCGA database,including 49 patients with complete response,2 patients with partial response,2 patients with stable diseases,and 12 patients with disease progressed. The patients with complete response were defined as chemotherapy sensitive,while the rest was defined as chemotherapy resistant. The 22 q12. 2 and Xp11. 23 were amplified in patient＇s cancer tissues with chemotherapy resistant,and the 1 q44 was deleted in patient＇s cancer tissues with chemotherapy resistant. The hot plot of 22 q12.2 was the gene of leukemia inhibitory factor（ LIF）,the hot plot of Xp11.23 was genes of porcupine homolog-drosophila（ PORCN） and emopamil binding protein（ EBP）; the hot plot of 1 q44 was the gene of kinesin family member 26 B（ KIF26 B）. Clinical analysis showed that amplification of LIF and PORCN/EBP on DNA levels was correlated with patients with chemotherapy resistant（ P〈0.05）,while deletion of KIF26 B was not significantly correlation（ P〈0.05）. CONCLUSION Amplification of 22 q12.2（ LIF）and Xp11.23（ PORCN/EBP） might be involved in the chemotherapy of endometrial cancer.
作者
刘琼茹
杨文丽
蔡育波
梁津杰
余卫东
方晓华
黄辉
陈艳虹
陈仙兰
张鑫
林碧华
LIU Qiongru;YANG Wenli;CAI Yubo;LIANG Jinjie;YU Weidong;FANG Xiaohua;HUANG Hui;CHEN Yanhong;CHEN Xianlan;ZHANG Xin;LIN Bihua(Department of Pathology, Jiangmen Central Hospital, Jiangmen, Guangdong 529030, China;Gnangdong Medical University, Key Laboratory for Medical Molecular Diagnostics of Guangdong Province, Dongguan , Guangdong 523808, China;Department of Biochemistry and Molecular Biology, Guangdong Medical University, Dongguan, Guangdong 523808, China)
出处
《今日药学》
CAS
2018年第3期179-183,共5页
Pharmacy Today
基金
国家自然科学基金项目(81272434)
广东省医学科研基金项目(A2016395,A2017103)
广东省中医药局科研项目(2017208520181273)
东莞市医疗卫生科技计划项目(2016105101292)
