基于TCGA数据分析NEK2基因在恶性胸膜间皮瘤中的表达及预后意义  

Analysis of expression and prognostic significance of NEK2 genein malignant pleural mesothelioma based on TCGA data

作　　者：李锦松 李彬 刘如爱 普元倩 自加吉 余敏 熊伟 LI Jinsong;LI Bin;LIU Ruai;PU Yuanqian;ZI Jiaji;YU Min;XIONG Wei(Department of Biochemistry and Molecular Biology,School of Basic Medical Sciences,Dali University,Dali 671000,Yunnan,China;Yunnan Provincial Key Laboratory of Insect Biomedicine Research and Development,Dali 671000,Yunnan,China;Yunnan Provincial Key Laboratory of Clinical Biochemistry,Dali 671000,Yunnan,China;Laboratory of Biochemistry and Molecular Biology of College of Life Sciences,Yunnan University,Kunming 650091,Yunnan,China)

机构地区：[1]大理大学基础医学院生物化学与分子生物学教研室,云南大理671000 [2]云南省昆虫生物医药研发重点实验室,云南大理671000 [3]云南省高校临床生物化学检验重点实验室,云南大理671000 [4]云南大学生命科学学院生物化学与分子生物学实验室,云南昆明650091

出　　处：《右江医学》2024年第2期103-111,共9页Chinese Youjiang Medical Journal

基　　金：国家自然科学基金(82160516);云南省应用基础研究专项面上项目(202201AT070004,202301AT070023);云南省地方本科高校基础研究联合专项面上项目(202101BA070001-226);云南省地方本科高校基础研究联合专项青年项目(202101BA070001-282);云南省昆虫生物医药研发重点实验室开放课题(AG2022003,AP2022006)。

摘　　要：目的 分析永不有丝分裂基因A相关激酶2(NEK2)基因在恶性胸膜间皮瘤(MPM)中的表达及预后意义。方法 下载癌症基因组图谱(TCGA)数据库MPM基因表达数据、临床病理数据和生存状态数据;使用perl软件和R语言的limma、timeROC等程序包作NEK2基因在MPM中的差异分析、临床病理相关性分析、COX单因素和多因素分析以及基因富集分析,并绘制ROC曲线;利用TIMER2.0数据库分析MPM中NEK2表达与常见的免疫细胞浸润的相关性。选取12例MPM组织和6例非MPM胸膜组织,通过RT-qPCR的方法验证NEK2基因在MPM与非瘤组织中的表达情况。结果 与正常肺组织相比,NEK2在MPM组织中高表达(P<0.001)。NEK2基因mRNA表达量与MPM淋巴结分期具有显著相关性(P<0.05);NEK2高表达与MPM患者预后不良相关(P<0.001);NEK2基因表达与MPM中B淋巴细胞、巨噬细胞、树突状细胞浸润水平呈正相关(P<0.05),并在细胞周期、DNA复制、剪接体、mRNA监测等通路显著富集。在收集到的病例样本中,与非MPM胸膜组织相比,NEK2基因在MPM组织中的表达量显著增高(P<0.01)。结论 NEK2在MPM组织中高表达,且NEK2在MPM中高表达提示预后不良,可能成为治疗MPM的潜在靶点。Objective To analyse the expression and prognostic significance of the never-expressed mitogen A-related kinase 2(NEK2)gene in malignant pleural mesothelioma(MPM).Methods The gene expression data,clinicopathological data and survival status data of MPM were downloaded from the cancer genome atlas(TCGA)database,and perl software and R language packages such as limma and timeROC were used to make differential analysis of NEK2 gene in MPM,clinicopathological correlation analysis,COX unifactorial and multifactorial analysis as well as gene set enrichment analysis,and the ROC curve was plotted;and TIMER2.0 database was used to analyze correlation between NEK2 expression in MPM and common immune cell infiltration.12 MPM tissues and 6 non MPM pleural tissues were selected,and the expression of NEK2 gene in MPM and non tumor tissues was verified by RT-qPCR.Results NEK2 was highly expressed in MPM tissues compared with normal lung tissues(P<0.001).mRNA expression of NEK2 gene was significantly correlated with MPM lymph node staging(P<0.05),high expression of NEK2 was correlated with poor prognosis of MPM patients(P<0.001);and the expression of NEK2 gene was positively correlated with the infiltration levels of B-lymphocytes,macrophages,and dendritic cells in MPM(P<0.05),and they were significantly enriched in pathways such as cell cycle,DNA replication,spliceosome,mRNA monitoring,etc.In the collected case samples,compared with non MPM pleural tissue,the expression level of NEK2 gene in MPM tissue was significantly increased(P<0.01).Conclusion NEK2 is highly expressed in MPM tissues,and the high expression of NEK2 in MPM suggests a poor prognosis,which may be a potential therapeutic target for MPM.

关 键 词：恶性胸膜间皮瘤 永不有丝分裂基因A相关激酶2 癌症基因组图谱 预后 生物信息学 

分 类 号：R734.3[医药卫生—肿瘤]