基于TCGA数据库数据分析肺腺癌组织中ESYT3基因的表达变化、临床意义及其分子作用机制

Expression changes,clinical significance,and molecular mechanism of ESYT3 gene in lung adenocarcinoma based on TCGA database

目的基于TCGA数据库数据分析肺腺癌组织中扩展突触标记蛋白3(ESYT3)基因的表达变化和临床意义,并探讨其分子作用机制。方法从TCGA数据库中下载肺腺癌患者的临床相关资料,观察肺腺癌组织和正常肺组织中ESYT3 RNA的表达量、ESYT3 DNA甲基化水平。以肺腺癌组织中ESYT3 RNA表达量中位值为界,将肺腺癌患者分为低表达组和高表达组,单因素Logistic回归分析ESYT3 RNA高、低表达与肺腺癌患者临床病理特征的关系,采用Kaplan-Meier法分析ESYT3 RNA高、低表达组患者中位生存期。通过R语言“limma”包筛选ESYT3 RNA高、低表达组患者的差异表达基因,并对低表达组中的差异表达基因进行GO生物过程富集分析和KEGG信号通路富集分析。提取KEGG细胞周期信号通路相关基因,分析其在ESYT3 RNA高、低表达组患者的差异表达情况,并利用Pearson相关性分析ESYT3与差异表达基因的相关性。结果肺腺癌组织中ESYT3 RNA的表达量为1.335(0.704,2.546),正常肺组织中ESYT3 RNA的表达量为3.953(2.986,4.737),两者相比,P<0.001。肺腺癌组织中ESYT3 DNA甲基化水平高于正常肺组织(P<0.01)。ESYT3 RNA高、低表达与肺腺癌患者性别、临床分期和T分期有关(P均<0.05)。低表达组肺腺癌患者中位生存期低于高表达组(P<0.01)。共筛选出ESYT3 RNA高、低表达组患者的差异表达基因1396个,GO生物学过程和KEGG信号通路富集分析结果显示,ESYT3低表达组中表达上调的基因主要在细胞周期等相关通路富集。共筛选出BUB1、BUB1B、CCNA2等26个参与KEGG细胞周期信号通路的差异表达基因,相关性分析结果显示,ESYT3与CCNA2、MAD2L1、PLK13个基因表达中度负相关。结论ESYT3基因在肺腺癌组织中低表达,ESYT3表达水平与患者性别、临床分期、T分期、生存期有关。ESYT3低表达影响细胞周期等信号通路,并与CCNA2、MAD2L1、PLK1等基因的表达呈负相关关系。

Objective To analyze the expression changes and clinical significance of ESYT3 gene in lung adenocarcinoma(LUAD),and to explore its molecular mechanism based on TCGA database.Methods The clinical data of LUAD patients were downloaded from TCGA database.The expression and DNA methylation of ESYT3 in LUAD and normal lung tissues were analyzed.Patients were divided into the high expression and low expression groups based on the median expression of ESTY3.Univariate Logistic regression was used to analyze the correlation between the expression of ESYT3 and clinicopathologic parameters of LUAD patients.Kaplan-Meier method was used to analyze the median survival time of the patients.The differentially expressed genes identified by R package“Limma”between the high and low expression groups,were subjected to GO and KEGG pathway enrichment analysis.KEGG cell cycle signaling pathway-related genes were selected.The relationship between the expression of ESYT3 and differentially expressed genes were determined by the Person correlation method.Results The expression levels of ESYT3 RNA were 1.335(0.704,2.546)in LUAD,and 3.953(2.986,4.737)in the normal lung tissues(both P<0.001).The methylation level of ESYT3 DNA in LUAD was higher than that in the normal lung tissues(P<0.01).The expression of ESYT3 RNA was related to sex,clinical stage,and T stage of LUAD patients(all P<0.05).The median survival time of LUAD patients was lower in the low ESYT3 expression group than in the high ESYT3 expression group(P<0.01).A total of 1396 differentially expressed genes were identified between the high and low ESYT3 expression groups,and the up-regulated genes in the low ESYT3 expression group were mainly enriched in cell cycle-related pathways.Twenty-six genes involved in cell cycle pathway were expressed differently in the high and low ESYT3 expression groups,and ESYT3 was moderately negatively correlated with the expression of CCNA2,MAD2L1 and PLK1 genes.Conclusions The expression of ESYT3 gene decreased in LUAD,and the expression of ESYT3 was correlated with the sex,clinical stage and T stage.Low expression of ESYT3 affected cell cycle signaling pathways and was negatively correlated with the expression of CCNA2,MAD2L1 and PLK1 genes.