基于生物信息数据库探讨肺腺癌中ECT2基因的表达和临床意义

Analysis of the expression and clinical significance of ECT2 gene in lung adenocarcinoma based on bioinformatics database

目的基于生物信息数据库探讨肺腺癌中上皮序列转化2(ECT2)基因的表达和临床预后意义。方法从TCGA、GEO、Sangerbox等生物信息数据库获取肺腺癌组织中ECT2基因的表达数据和临床病理特征参数,比较肺腺癌和癌旁组织中ECT2的表达差异,分析ECT2表达与临床特征、表皮生长因子受体(EGFR)突变状态的相关性,探讨ECT2作为独立预后因素评估患者预后的意义,通过基因集富集分析(GSEA)挖掘ECT2参与的信号通路,利用ESTIMATE算法评估ECT2表达与肺腺癌微环境中免疫细胞浸润程度的相关性。结果在TCGA、GSE31210、GSE40791、GSE10072、GSE32863、GSE75037数据库中,肺腺癌组织中ECT2基因的表达均显著高于正常组织(P<0.001)。ECT2表达与性别、吸烟情况、T分期、N分期、TNM分期密切相关,且在EGFR突变的患者中表达显著降低(P<0.05)。ECT2高表达可作为肺腺癌患者预后的独立危险因素,联合T分期和N分期的列线图模型能更准确地预测患者的预后。GSEA分析表明,ECT2高表达患者存在mTORC1通路、未折叠蛋白反应、有丝分裂纺锤体、Myc靶点、G 2/M细胞周期检查点、E2F靶点、DNA损伤修复等信号通路激活富集。ESTIMATE算法结果显示,ECT2表达与基质评分、免疫评分、ESTIMATE评分呈负相关,并与B细胞、CD4+T细胞和中性粒细胞浸润程度密切相关。结论ECT2在肺腺癌患者中高表达,是恶性生物学表型及不良预后的独立危险因素,且与EGFR基因突变状态及肿瘤微环境中的免疫细胞浸润密切相关,可作为治疗筛选及预后监测的潜在生物标志物。

Objective To explore the expression and clinical prognostic significance of epithelium cell transforming sequence 2(ECT2)gene in lung adenocarcinoma based on bioinformatics database.Methods We obtained ECT2 gene expression data and clinicopathological characteristics parameters in lung adenocarcinoma tissues from bioinformatics databases including TCGA,GEO,and Sangerbox.Then we compared the differences in ECT2 expression in lung adenocarcinoma and adjacent tissues,analyzed the correlation of ECT2 expression with clinical characteristics and epidermal growth factor receptor(EGFR)mutation status,explored the significance of ECT2 as an independent prognostic factor to assess patient prognosis,mined the signaling pathways involved in ECT2 by gene set enrichment-analysis(GSEA),and assessed the correlation between ECT2 expression and the degree of immune cell infiltration in the microenvironment of lung adenocarcinoma using ESTIMATE algorithm.Results In the TCGA,GSE31210,GSE40791,GSE10072,GSE32863 and GSE75037 databases,the expression of ECT2 gene in lung adenocarcinoma tissues was significantly higher than that in adjacent tissues(P<0.001).ECT2 expression was strongly correlated with gender,smoking status,T-stage,N-stage and TNM-stage,and was significantly lower in patients with EGFR mutation(P<0.05).High ECT2 expression showed as an independent prognostic risk factor for lung adenocarcinoma patients,and the nomogram model combining T-stage and N-stage could more accurately predict the prognosis of patients.The GSEA analysis showed that patients with high ECT2 expression were enriched for activation of signaling pathways such as mTORC1 signaling,unfolded protein response,mitotic spindle,Myc targets,G 2/M checkpoint,E2F targets and DNA repair.ESTIMATE algorithm results showed that ECT2 expression was correlated with stromal score,immune score,and with B cells,CD4+T cells,and neutrophil granulocyte infiltration(P<0.05).Conclusion ECT2 is highly expressed in patients with lung adenocarcinoma and is an independent risk factor for malignant phenotype and poor prognosis,and is closely associated with EGFR mutation status and immune cell infiltration in the tumor microenvironment,which can be used as a potential biomarker for therapeutic screening and prognostic monitoring.