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(Keapl)mRNA for lung cancer,and to explore possible mechanisms.Diagnostic performance of Keapl mRNA was determined by receiver operating characteristic(ROC)curve analysis.Prognostic implication of Keapl mRNA was estimated by Kaplan-Meier survival analysis.Co-expressed genes with both Keapl and Nfe2L2 were identified by LinkedOmics.Mechanisms of Keapl-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 Keapl 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 Keapl 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 Keapl and Nfe2L2 for LUAD,and 22 for LUSC,mainly enriched in signaling pathway of oxidative stress-induced gene expression via Nrf2.In conclusion,Keapl mRNA has a good diagnostic performance,but controversial prognostic efficacy for LUSC.The pathogenesis of lung cancer is associated with Keapl-Nfe2L2-co-expressed genes by signaling pathway of oxidative stress-induced gene expression via Nrf2.
