铜死亡基因在子宫内膜癌中的预后意义  

Prognostic significance of copper death gene in endometrial cancer

作　　者：张亚萍 李朝明 韩红 刘红艳 冲喜会 刘小凤 陈凡 魏林珍 张芸中[5,6] 秦天生 Zhang Yaping;Li Chaoming;Han Hong;Liu Hongyan;Chong Xihui;Liu Xiaofeng;Chen Fan;Wei Linzhen;Zhang Yunzhong;Qin Tiansheng(Department of Obstetrics and Gynecology,Pingliang Second People's Hospital,Pingliang,744000,China;Departmeat of Urinary Surgery,The First People's Hospital of Longnan,Longnan 742500,China;Obstetrics and Gynecology,The First People's Hospital of Longnan,Longnan 742500,China;The First Clinical Medical School,Gansu University of Chinese Medicine,Lanzhou 730000,China;Department of Obstetrics and Gynecology,Second Hospital of Lanzhou University,Lanzhou 730030,China;The Second Clinical Medical School,Lanzhou University,Lanzhou 730000,China)

机构地区：[1]平凉市第二人民医院妇产科,甘肃平凉744000 [2]陇南市第一人民医院泌尿外科,甘肃陇南742500 [3]陇南市第一人民医院妇产科,甘肃陇南742500 [4]甘肃中医药大学第一临床医学院,甘肃兰州730000 [5]兰州大学第二医院妇产科,甘肃兰州730000 [6]兰州大学第二临床医学院,甘肃兰州730000

出　　处：《兰州大学学报（医学版）》2023年第6期55-61,共7页Journal of Lanzhou University（Medical Sciences）

基　　金：甘肃省教育厅重大专项资助项目(LCCX2021011);甘肃省中医药管理局科研资助项目(GZKG-2021-52);甘肃省自然科学基金资助项目(20JR5RA332);兰州市科技局科研资助项目(2020-RC-52)。

摘　　要：目的近年来铜死亡机制备受关注,但它在子宫内膜癌中的作用机制尚不清楚,本文探讨了铜死亡相关基因在子宫内膜癌中的预后与应用价值。方法使用癌症基因组图谱(TCGA)数据库获取原始数据,“limma”软件包用于鉴定癌组织和正常组织之间的差异表达基因;“ConsensusClusterPlus”包将子宫内膜癌病例分为两个亚组;“ggplot2”分析分型间差异基因与临床特征间的相关性,最后通过环氧合酶分析确定与子宫内膜癌患者预后相关的铜死亡基因。基于铜死亡基因鉴定了子宫内膜癌的亚型(C1、C2),分析2个亚型与富集的信号通路、总生存期(OS)、临床特征和免疫浸润的相关性。结果在10个铜死亡基因中筛选出子宫内膜癌组织与正常癌旁组织中差异表达的6个基因。功能富集分析表明C1激活了癌症相关的信号通路,C2激活了抑癌相关的信号通路,差异有统计学意义(P<0.05)。C1的OS大于C2,二者差异有统计学意义(P<0.001)。病理分级、分期、年龄等临床特征在2个亚型中存在显著差异(P<0.05)。与C2相比,C1存在更大的免疫细胞浸润(P<0.05)。结论基于铜死亡基因,可鉴定子宫内膜癌的亚型,基因PDHA1、GLS、CDKN2A与子宫内膜癌预后存在相关性。Objective The mechanism of copper death has attracted much attention in recent years,but its mechanism of action in endometrial cancer is still unclear.This paper explored the prognostic and application value of copper death-related genes in endometrial cancer.Methods Raw data were acquired using TCGA database;the"limma"package was used to identify differentially expressed genes between cancerous and normal tissues.Endometrial cancer cases were divided into two subgroups using the"ConsensusClusterPlus"package;correlations between differential genes and clinical characteristics were analyzed using"ggplot2",and finally,copper death genes associated with prognosis in endometrial cancer patients were identified by Cox analysis.Overall,endometrial cancer subtypes(C1 and C2)were identified based on copper death genes,and the correlation between the two subtypes and enriched signaling pathways,overall survival(OS),clinical features,and immune infiltration were all analyzed.Results Screened were 6 out of 10 copper death genes differentially expressed in endometrial cancer tissues and normal paracancerous tissues.Functional enrichment analysis showed that C1 activated cancer-related signaling pathways and C2 activated cancer-inhibitingrelated signaling pathways,with statistically significant differences(P<0.05).Overall survival(OS)analysis showed a statistically significant difference in superior OS in C1 compared to C2(P<0.001).Clinical characteristics,including pathological grading,staging and age,were significantly different between the two groups in both subtypes(P<0.05).Conclusion Based on copper death genes,subtypes of endometrial cancer were identified,and analysis identified PDHA1,GLS and CDKN2A as genes associated with prognosis of endometrial cancer.

关 键 词：铜死亡 子宫内膜癌 预后 生物信息学 

分 类 号：R737.33[医药卫生—肿瘤]