基于TCGA数据库分析GTSE1基因在肺腺癌中的表达及意义

Expression and significance of GTSE1 gene in lung adenocarcinoma based on TCGA database

目的:探究G2/S期表达蛋白1(G2 and S phase-expressed protein1,GTSE1)在肺腺癌中的表达情况以及对预后的影响。方法:从癌症基因组图谱(TCGA)数据库中下载肺腺癌患者表达谱数据以及临床信息资料,分析GTSE1表达水平与临床指标信息之间的相关性及对预后的影响,并用Cox比例风险回归模型分析影响患者预后的因素。采用免疫组化检测14例肺腺癌肿瘤组织和13例癌旁组织中GTSE1表达水平。采用基因集富集分析方法(GSEA)预测GTSE1在肺腺癌中可能参与并调控的相关通路。结果:在TCGA数据中,在肿瘤组织样本中GTSE1基因表达情况明显高于正常组织(t=18.165,P<0.05),且表达水平与肿瘤分级(χ^(2)=17.543,P=0.001)、T(χ^(2)=8.825,P=0.032)和N分期(χ^(2)=12.138,P=0.001)之间有显著相关,GTSE1高表达患者的总生存期显著低于GTSE1低表达的患者(χ^(2)=22.663,P<0.05),单因素Cox分析提示肿瘤分级(HR=1.56,95%CI:1.33~1.83)、TNM分期(T:HR=1.60,95%CI:1.31~1.95;N:HR=1.70,95%CI:1.40~2.06;M:HR=1.83,95%CI:1.03~3.25)和GTSE1表达水平(HR=2.32,95%CI:1.62~3.30)可影响患者的总生存期(均P<0.05)。多因素Cox分析提示T分期(HR=1.646,95%CI:1.038~2.610,P=0.034)和GTSE1的表达水平(HR=1.830,95%CI:1.269~2.637,P<0.05)是影响肺腺癌患者总生存期的独立危险因素。GTSE1基因高表达的样本在细胞周期以及p53信号通路等9个通路基因集中富集(P<0.05,FDR<0.01)。结论:GTSE1在肺腺癌患者肿瘤组织中显著高表达,是肺腺癌患者的独立预后因素。

Objective:To explore the expression of G2 and S phase-expressed protein 1(GTSE1)in lung adenocarcinoma and its effect on prognosis.Methods:The expression profile data and clinical information of patients with lung adenocarcinoma were downloaded from the Cancer Genome Atlas(TCGA)database to analyze the correlation between GTSE1 expression and clinical indicator information and its influence on prognosis,and Cox proportional hazard regression model was used to analyze the factors affecting the prognosis of patients.Immunohistochemistry was used to detect GTSE1 expression in 14 lung adenocarcinoma tumor tissues and 13 adjacent tissues.Gene set enrichment analysis(GSEA)was used to predict the relevant pathways that GTSE1 might participate in and regulate lung adenocarcinoma.Results:In the TCGA database,GTSE1 gene expression in tumor tissue samples was obviously higher than that of normal tissue(t=18.165,P<0.01),and the expression and tumor grade(χ^(2)=17.543,P=0.001),T(χ^(2)=8.825,P=0.032)and N stage(χ^(2)=12.138,P=0.001)had a significant correlation.The overall survival of patients with high expression of GTSE1 was significantly lower than that of patients with low expression of GTSE1(χ^(2)=22.663,P<0.05).Single factor analysis of Cox suggested tumor grade(HR=1.56,95%CI:1.33~1.83),TNM staging(T:HR=1.60,95%CI:1.31~1.95;N:HR=1.70,95%CI:1.40~2.06;M:HR=1.83,95%CI:1.03~3.25)and GTSE1 expression(HR=2.32,95%CI:1.62~3.30)affected the patient′s overall survival(all P<0.05).Multi-factors Cox analysis indicated that T stage(HR=1.646,95%CI:1.038~2.610,P=0.034)and GTSE1 expression(HR=1.830,95%CI:1.269~2.637,P<0.05)were independent risk factors for overall survival of patients with lung adenocarcinoma.The samples with high GTSE1 gene expression were concentrated in 9 pathway genes including cell cycle and p53 signaling pathway(P<0.05,FDR<0.01).Conclusion:GTSE1 is highly expressed in the tumor tissues of patients with lung adenocarcinoma,and is an independent prognostic factor for patients with lung adenocarcinoma.