基于数据挖掘分析ERO1L在肺腺癌中的表达及临床意义

Expression and clinical significance of ERO1L in lung adenocarcinoma through data mining

目的探索内质网氧化还原1样蛋白(endoplasmic reticulum oxidoreductin-1-like protein,ERO1L)在肺腺癌中的表达及意义。方法利用c Bio Portal在线分析癌症基因图谱(The Cancer Genome Atlas,TCGA)数据库中586例肺腺癌样本中的RNA-Seq数据,并结合患者的完整生存时间信息,采用KaplanMeier法分析ERO1L变异与肺腺癌患者生存之间的关系。通过基因表达谱动态分析(Gene Expression Profiling Interactive Analysis,GEPIA)数据库搜索ERO1L mRNA在正常肺组织与肺腺癌组织表达的情况,分析其在不同TNM分期中的表达情况。用MethHC数据库分析ERO1L基因在肺腺癌中的甲基化水平。String-DB数据库分析与ERO1L相互作用的蛋白。结果在230例肺腺癌样本中有18例发生ERO1L基因变异,变异率为8%。Kaplan-Meier生存曲线分析显示ERO1L变异组总体生存期(overall survival,OS)短于无变异组(P=0. 0268)。肺腺癌组织中ERO1L mRNA表达明显高于正常肺组织(P <0. 05),且其启动子甲基化水平显著减低(P <0. 005)。ERO1LB、ERP29、ERP44、GPX7、GPX8、INS、P4HB、PDIA4、PDIA6、TXNDC5等基因与ERO1L有明显的相互作用。结论通过肿瘤基因数据库信息挖掘表明,ERO1L在肺腺癌组织中呈高表达,且与患者预后不良相关,为深入研究ERO1L在肺腺癌发生发展中的作用提供重要理论依据。

Objective To explore the expression and significance of endoplasmic reticulum oxidoreductin-1-like protein （ERO1L） in lung adenocarcinoma. Methods The clinical data of 586 patients with RNA-Seq in the Cancer Genome Atlas （TCGA） database were analyzed by cBioPortal online analysis platform. Kaplan-Meier method was used to analyze the relationship between the ERO1L genetic alteration and lung adenocarcinoma survival. The expression of ERO1L mRNA in normal lung tissues and lung adenocarcinoma tissues was searched through Gene Expression Profiling Interactive Analysis （GEPIA） database, and the expression of ERO1L mRNA in different TNM stages was analyzed. ERO1L gene methylation level was analyzed by using the MethHC database. The ERO1L-interacting proteins were analyzed by String-DB database. Results In 230 patients, mutation of ERO1L gene was found in 18 patients with a mutation rate of 8%. Kaplan-Meier curve showed that overall survival （OS） of patients with ERO1L genetic alteration was significantly shorter than that in patients without ERO1L genetic alteration （ P =0.0268）. At the mRNA level, ERO1L was higher in lung adenocarcinoma than normal lung tissue （ P〈 0.05）. The methylation of ERO1L promoter in lung adenocarcinoma was decreased （ P〈 0.005）. The ERO1LB, ERP29, ERP44, GPX7, GPX8, INS, P4HB, PDIA4, DIA6, TXNDC5 and other genes had obvious interaction with ERO1L. Conclusion According to the information mining of tumor gene database, ERO1L mRNA is found highly expressed in lung adenocarcinoma tissue and the expression of ERO1L has a significant impact on prognosis of lung adenocarcinoma patients, which provides an important theoretical basis for further studying the role of ERO1L in the occurrence and development of lung adenocarcinoma.