EXO1的高表达是肺腺癌预后不良的独立预测因子  

High Expression of EXO1 is an Independent Predictor of Poor Prognosis of Lung Adenocarcinoma

作　　者：朱娅霖 王永红 梁阳 冯文莉[1] 袁颖[2] Zhu Yalin;Wang Yonghong;Liang Yang;Feng Wenli;Yuan Ying(Key Laboratory of Medical Diagnostics of Ministry of Education,Faculty of Laboratory Medicine,Chongqing Medical University,Chongqing,400016;Department of Respiratory and Critical Care Medicine,The First Affiliated Hospital of Chongqing Medical University,Chongqing,400016)

机构地区：[1]重庆医科大学检验医学院,临床检验诊断学教育部重点实验室,重庆400016 [2]重庆医科大学附属第一医院呼吸与危重症医学科,重庆400016

出　　处：《基因组学与应用生物学》2022年第3期691-698,共8页Genomics and Applied Biology

基　　金：国家自然科学基金项目(81703095);重庆市自然科学基金项目(cstc2021jcyj-msxmX0214)共同资助

摘　　要：核酸外切酶1(exonuclease 1,EXO1)已被证明在一些肿瘤中可作为具有临床意义的生物标志物,然而其在肺腺癌中的作用尚不清楚。为了研究EXO1在肺腺癌中的作用,我们首先利用癌症基因组图谱数据集(the cancer genome atlas,TCGA)对肺腺癌患者各临床特征与EXO1表达量之间的关系进行了生物信息学分析,并通过蛋白质免疫印迹和CCK-8实验在肺腺癌细胞株中进行验证。结果显示,EXO1在肺腺癌中呈现高表达,并且其表达程度与肺腺癌的临床分期相关,我们推测EXO1是影响肺腺癌总体生存的独立危险因素;此外,通过基因富集分析确定了EXO1与DNA传感途径、碱基切除修复、DNA复制、细胞周期、P53信号通路和ERBB信号通路有关,这些途径在高EXO1表达的肺腺癌中高度富集。蛋白免疫印迹和CCK-8实验结果显示,EXO1在肺腺癌细胞中高表达,干扰EXO1表达水平可以抑制肺腺癌细胞的增殖能力。本研究证明了EXO1在肺腺癌的中高表达水平,它可以作为潜在的独立预后分子标志物,为肺腺癌患者的诊断治疗和预后评价提供新思路。Exonuclease 1(EXO1)has been reported as a potential biomarker in various cancers.However,its role in lung adenocarcinoma is poorly understood.To investigate the role of EXO1 in lung adenocarcinoma,we used the cancer genome atlas(TCGA)dataset to evaluate the relationship between the clinical features and EXO1 expression in the lung adenocarcinoma patients with bioinformatics analysis.The results were further verified in lung adenocarcinoma cell lines by Western blot and CCK-8 assay.The results showed that EXO1 was highly expressed in lung adenocarcinoma and its expression was related to the TNM staging of lung adenocarcinoma.EXO1 was proved to be an independent risk factor for overall survival.In addition,Gene set enrichment analysis(GSEA)determined that EXO1 was associated with the DNA sensing pathway,base excision repair,DNA replication,cell cycle,P53 signaling pathway,and ERBB signaling pathway.These pathways are highly enriched in lung adenocarcinoma with high EXO1 expression.Western blot and CCK-8 assays showed that EXO1 was highly expressed in lung adenocarcinoma cell lines.Moreover,targeting EXO1 inhibited the proliferation of lung adenocarcinoma cells.This study discovered that EXO1 was highly expressed in lung adenocarcinoma and is a potential independent prognostic biomarker,providing new insights for the diagnosis,treatment,and prognosis evaluation of lung adenocarcinoma patients.

关 键 词：肺腺癌 EXO1 基因表达 预后因子 

分 类 号：R734.2[医药卫生—肿瘤]