Diagnostic and Prognostic Significance of Keap1 mRNA Expression for Lung Cancer Based on Microarray and Clinical Information from Oncomine Database

• 作者: Guang-ya LIU Wei ZHANG Xu-chi CHEN Wen-juan WU Shi-qian WAN
• 来源期刊: 当代医学科学（英文）
• 年，卷（期）: 2021,（3）
• 所属期刊栏目: ORIGINAL ARTICLES
• 页码范围: 597-609
• 页数: 13页
• 语种: 英文
• DOI: 10.1007/s11596-021-2378-2

摘要

We performed a bioinformatics analysis with validation by multiple databases,aiming to evaluate the diagnostic and prognostic value of Kelch-like ECH-associated protein 1(Keap1)mRNA for lung cancer,and to explore possible mechanisms.Diagnostic performance of Keap1 mRNA was determined by receiver operating characteristic(ROC)curve analysis.Prognostic implication of Keap1 mRNA was estimated by Kaplan-Meier survival analysis.Co-expressed genes with both Keap1 and Nfe2L2 were identified by LinkedOmics.Mechanisms of Keap1-Nfe2L2-co-expressed genes underlying the pathogenesis of lung cancer were explored by function enrichment and pathway analysis.The ROC curve analysis determined a good diagnostic performance of Keap1 mRNA for lung squamous cell carcinoma(LUSC),with an area under the ROC curve(AUC)of 0.833,sensitivity of 72.7％,and specificity of 90.6％(P＜0.001).Multivariate Cox regression recognized high Keap1 mRNA to be an independent risk factor of mortality for overall lung cancer[hazard ratio(HR):11.034,P=0.044],but an independent antagonistic factor for lung adenocarcinoma(LUAD)(HR:0.404,P＜0.001).Validation by UALCAN and GEPIA supported Oncomine findings regarding the diagnostic value of Keapl mRNA for LUSC,but denied its prognostic value.After screening,we identified 17 co-expressed genes with both Keap1 and Nfe2L2 for LUAD,and 22 for LUSC,mainly enriched in signaling pathway of oxidative stress-induced gene expression via Nrf2.In conclusion,Keap1 mRNA has a good diagnostic performance,but controversial prognostic efficacy for LUSC.The pathogenesis of lung cancer is associated with Keap1-Nfe2L2-co-expressed genes by signaling pathway of oxidative stress-induced gene expression via Nrf2.