子宫内膜癌组织中GPX4、ELK1表达变化及其与上皮—间充质转化和预后的关系OACSTPCD
Expression changes of GPX4 and ELK1 in endometrial cancer tissues and their relationships with EMT and prognosis
目的 观察子宫内膜癌(EC)组织中谷胱甘肽过氧化物酶4(GPX4)、含ETS域转录因子Elk1(ELK1)表达变化,分析二者与上皮—间充质转化(EMT)及预后的关系.方法 EC患者90例,留取肿瘤组织与癌旁正常组织,采用免疫组化法检测GPX4、ELK1蛋白,采用实时荧光定量PCR法检测GPX4 mRNA、ELK1 mRNA及EMT相关基因[E-钙黏素(E-cad)、N-钙黏素(N-cad)、碱性螺旋—环—螺旋转录因子(TWIST)mRNA].采用Pearson相关分析法分析EC组织中GPX4 mRNA、ELK1 mRNA与E-cad mRNA、N-cad mRNA、TWIST mRNA表达的相关性.采用R软件分析癌症基因组图谱数据库中EC的RNA-seq数据,绘制Kaplan-Meier曲线,比较不同GPX4、ELK1 mRNA表达情况EC患者的预后.结果 EC组织中GPX4、ELK1蛋白阳性表达率高于癌旁组织(P均<0.05).EC组织中GPX4、ELK1、N-cad、TWIST mRNA表达高于癌旁组织,E-cad mRNA表达低于癌旁组织(P均<0.05).EC组织中GPX4 mRNA与ELK1 mRNA表达呈正相关;GPX4 mRNA、ELK1 mRNA表达与E-cad mRNA表达呈负相关,与N-cad mRNA、TWIST mRNA表达呈正相关(P均<0.05).EC组织中GPX4、ELK1 mRNA表达与FIGO分期、组织学分级和淋巴结转移有关,FIGO分期越高、组织学分级越高、有淋巴结转移者肿瘤组织中GPX4、ELK1 mRNA表达更高(P均<0.05).GPX4 mRNA高表达组、ELK1 mRNA高表达组5年总生存率分别低于低表达组(P均<0.05).结论 EC组织中GPX4、ELK1呈高表达,二者表达与EMT、患者预后有关,有望成为EC患者预后评估的标志物.
Objective To observe the expression changes of glutathione peroxidase 4(GPX4)and ETS-domain tran-scription factor Elk-1(ELK1)in endometrial cancer(EC)tissues,and to investigate their relationships with epithelial-mesenchymal transition(EMT)and prognosis.Methods Ninety patients with EC were selected,and the tumor tissues and adjacent normal tissues were collected.The expression levels of GPX4 and ELK1 proteins in tissues were detected by immunohistochemical method.The expression of GPX4 mRNA,ELK1 mRNA,and EMT markers[E-cadherin(E-cad)mRNA,N-cadherin(N-cad)mRNA,and alkaline spiral ring spiral transcription factor(TWIST)mRNA]in tissues were detected by real-time fluorescent quantitative PCR.Pearson correlation analysis was performed on the correlation between GPX4 mRNA,ELK1 mRNA,E-cad mRNA,N-cad mRNA,and TWIST mRNA.R software was used to analyze the RNA-seq data of EC in the cancer genome map database,and Kaplan Meier curve was drawn to compare the prognosis of EC pa-tients with different GPX4 mRNA and ELK1 mRNA expression levels.Results The positive rates of GPX4 and ELK1 proteins in the EC tissues were higher than those in the adjacent tissues(both P<0.05).The GPX4 mRNA,ELK1 mRNA,N-cad mRNA,and TWIST mRNA in the EC tissues were higher than those in the adjacent tissues,while the E-cad mRNA was lower than that in the adjacent tissues,with statistically significant difference(all P<0.05).In the EC tissues,the expression of GPX4 mRNA was positively correlated with the expression of ELK1 mRNA;the expression levels of GPX4 mRNA and ELK1 mRNA were negatively correlated with the expression of E-cad mRNA,and were positively cor-related with the expression levels of N-cad mRNA and TWIST mRNA(all P<0.05).The expression levels of GPX4 mRNA and ELK1 mRNA in the EC tissues were related to FIGO staging,histological grading,and lymph node metastasis.The higher the FIGO staging,histological grading,and having lymph node metastasis,the higher expression levels of GPX4 mRNA and ELK1 mRNA in the EC tissues(all P<0.05).The 5-year overall survival rates of the high GPX4 mRNA expression group and high ELK1 mRNA expression group were lower than those of the low expression groups,respectively(both P<0.05).Conclusions In the EC tissues,GPX4 and ELK1 are highly expressed.Their expression levels are re-lated to EMT and the prognosis of patients,and are expected to become markers for prognostic evaluation of EC patients.
董瑞丽;毛建英;周秀枝
内蒙古自治区人民医院妇科,呼和浩特 010017
临床医学
子宫内膜癌谷胱甘肽过氧化物酶4含ETS域转录因子Elk1上皮—间充质转化
endometrial carcinomaglutathione peroxidase 4ETS-domain transcription factor Elk-1epithelial-mesenchymal transition
《山东医药》 2024 (020)
16-20 / 5
内蒙古自治区自然科学基金项目(2024MS08024);内蒙古医疗卫生科技计划项目(201901269).
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