结肠腺癌组织中谷胱甘肽过氧化物酶4的表达及其与患者临床病理特征和预后的关系  

Expression of glutathione peroxidases 4 in colon adenocarcinoma tissues and its relationship with clinicopathological features and prognosis of patients

作　　者：罗寿 刘文杰 苏昊 徐正 梁建伟 刘骞 周志祥 王锡山 周海涛 Luo Shou;Liu Wenjie;Su Hao;Xu Zheng;Liang Jianwei;Liu Qian;Zhou Zhixiang;Wang Xishan;Zhou Haitao(Department of Colorectal Surgery,Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,National Clinical Research Center for Cancer,National Cancer Center,Beijing 100021,China;Laboratory of Hepatological Surgery,Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,National Clinical Research Center for Cancer,National Cancer Center,Beijing 100021,China)

机构地区：[1]国家癌症中心,国家肿瘤临床医学研究中心,中国医学科学院,北京协和医学院肿瘤医院结直肠外科,北京100021 [2]国家癌症中心,国家肿瘤临床医学研究中心,中国医学科学院,北京协和医学院肿瘤医院肝胆外科实验室,北京100021

出　　处：《肿瘤研究与临床》2021年第8期572-578,共7页Cancer Research and Clinic

基　　金：中国医学科学院医学与健康科技创新工程(协同创新团队项目)(2017-12M-4-002);北京市东城区优秀人才计划;中国癌症基金会北京希望马拉松基金。

摘　　要：目的探讨谷胱甘肽过氧化物酶4(GPX4)在结肠腺癌中的表达情况及其与患者临床病理特征和预后的关系。方法在癌症基因组图谱(TCGA)数据库中获取结肠腺癌数据集,分析GPX4在结肠腺癌组织中的表达及其对总生存(OS)的预测价值。选取国家人类遗传资源共享服务平台提供的2009年11月至2010年5月行手术治疗的结肠腺癌组织93例及其配对癌旁组织87例,应用组织芯片免疫组织化学法检测GPX4蛋白表达水平。分析GPX4蛋白表达情况与结肠腺癌患者临床病理特征及OS的关系。采用Cox比例风险回归模型进行预后影响因素分析,建立和绘制预测OS率的列线图。结果对TCGA数据库数据分析显示,380例结肠腺癌患者中GPX4在结肠腺癌组织中的表达高于正常结肠黏膜组织[中位每千个碱基的转录每百万映射读取的片段数(FPKM)值:85.654(20.351~356.237)比56.230(48.783~63.931)],差异有统计学意义(Z=-6.150,P<0.05);GPX4高表达组(FPKM≥83.614)的OS较GPX4低表达组(FPKM<83.614)差(中位OS时间84.40个月比94.03个月,5年OS率58.6%比72.7%),差异有统计学意义(P<0.05)。组织芯片免疫组织化学染色结果显示,结肠腺癌组织GPX4蛋白高表达率高于癌旁正常组织[38.0%(35/92)比7.3%(6/82)],差异有统计学意义(χ^(2)=22.727,P<0.01);GPX4在左半结肠腺癌组织中的高表达率高于右半结肠腺癌组织[47.2%(25/53)比25.6%(10/39)],差异有统计学意义(χ^(2)=4.42,P=0.036);GPX4高表达组患者的5年OS率低于低表达组患者(25.7%比57.9%),差异有统计学意义(χ^(2)=9.051,P<0.05);多因素Cox比例风险回归模型分析结果显示,淋巴结转移(N1~N3期)(HR=2.241,95%CI 1.242~4.046,P=0.007)和GPX4高表达(HR=2.783,95%CI 1.598~4.848,P<0.01)是结肠腺癌患者不良预后的独立影响因素;应用上述因素建立预测结肠腺癌患者预后的列线图,C指数为0.739,提示该列线图具有较好的预测效能。结论GPX4在结肠腺癌组织中表达上调,且其高�Objective To investigate the expression of glutathione peroxidases 4(GPX4)in colon adenocarcinoma and its relationship with clinicopathological features and prognosis of patients.Methods The data set of colon adenocarcinoma was obtained from The Cancer Genome Atlas(TCGA)database to analyze the expression of GPX4 in colon adenocarcinoma tissues and its predictive value for overall survival(OS).A total of 93 colon adenocarcinoma tissues and 87 adjacent mucosa tissues after operation from November 2009 to May 2010 provided by the National Human Genetic Resources Sharing Service Platform were selected.The expression of GPX4 protein was detected by using tissue chip immunohistochemistry.The relations between the expression of GPX4 protein and the clinicopathological features and OS of colon adenocarcinoma patients were analyzed.Cox proportional hazards regression model was used to analyze the factors affecting the prognosis.The nomogram for predicting OS rate was established and drawn.Results The analysis of data from TCGA database showed that in 380 cases of colon adenocarcinoma,the expression of GPX4 in colon adenocarcinoma tissues were higher than that in the normal colonic mucosa tissues[the value of fragments per kilobase of exon per million fragments mapped(FPKM):85.654(20.351-356.237)vs.56.230(48.783-63.931)],and the difference was statistically significant(Z=-6.150,P<0.05).The OS in GPX4 high-expression group(FPKM≥83.614)were poorer than that in GPX4 low-expression group(FPKM<83.614)(median OS time:84.40 months vs.94.03 months,5-year OS rate:58.6%vs.72.7%),and the difference was statistically significant(P<0.05).Tissue chip immunohistochemical staining results show that the high-expression rate of GPX4 protein in colon adenocarcinoma tissues was higher than that in adjacent normal tissues[38.0%(35/92)vs.7.3%(6/82)],and the difference was statistically significant(χ^(2)=22.727,P<0.01);the high-expression rate of GPX4 protein in left colon adenocarcinoma tissues was higher than that in right colon adenocarcin

关 键 词：结肠肿瘤 腺癌 谷胱甘肽过氧化物酶4 预后 

分 类 号：R735.35[医药卫生—肿瘤]