Construction Of A Prognostic Risk Prediction Model For Patients With Lung Adenocarcinoma Based On Ferroptosis-related LncRNAs

Objective:Based on bioinformatics analysis of the potential correlation between ferroptosis-related lnc RNAs and the prognosis of lung adenocarcinoma(LUAD),a prognostic risk prediction model for patients with lung adenocarcinoma was constructed.METHODS:Downloaded RNA-sequencing(RNA-seq)data and corresponding clinical information of LUAD patients from The Cancer Genome Atlas(TCGA)database,extracted the expression of ferroptosis genes based on the Ferroptosis Database,and used the R language "limma package" to co-share lnc RNAs and ferroptosis-related genes expression analysis,found ferroptosis-related lnc RNAs,and then performed differentially expressed genes(DEGs)analysis on ferroptosis-related lnc RNAs,and screened out genes that were differentially expressed between normal samples and tumor samples.Combined the different lnc RNAs with the clinical survival data of LUAD patients to obtain survival-related lnc RNAs,and survival analysis of lnc RNAs associated with overall survival for model construction using R language "survival package" screened key genes associated with LUAD prognosis,construct a prognostic model for the prognostic-related lnc RNAs.According to the median risk score,LUAD patients were divided into high-risk and low-risk groups,Univariate and multivariate Cox regression analysis were used to evaluate whether the prognostic model was independent of other clinical features in predicting overall survival(OS)in patients with LUAD.Prognostic model was integrated with clinical characteristics,and comprehensive curves(including survival curve,ROC curve and risk curve)and clinical correlation heat map were drawn to verify the predictive ability of the model.Finally,functional enrichment analysis was performed on the differentially expressed genes.Gene enrichment analysis(GSEA),TIMER and other toolkits were used to conduct gene enrichment analysis and immune correlation analysis on the high-risk group and low-risk group,and the immune differences between the two groups were compared.RESULTS:Thirteen lnc RNAs with prognostic significance related to ferroptosis were screened out to construct a multi-gene prognostic risk prediction model,which were AL606489.1,AC069542.1,AL365181.3,AC034102.8,LINC01235,MEG3,MIR193 BHG,LINC02320,LINC00543,AC090559.1,AL049836.1,AF131215.5,and LINC00941.Univariate and multivariate Cox regression analysis showed that the prognostic model could predict OS of LUAD patients independently from other clinical features as an independent prognostic factor.Kaplan-Meier survival analysis,ROC curve,risk curve and clinical correlation heat map further proved that the model had accurate prediction ability.Among them,the overall survival time of the high-risk group and the low-risk group was significantly different(P <0.01),the prognosis of patients with LUAD in the high-risk group was significantly lower than that in low-risk group.In addition,based on the constructed prognostic risk prediction model,functional enrichment analysis showed that DEGs were mainly enriched in ferroptosis pathway,HIF-1 signaling pathway,cysteine and methionine metabolism pathway,and GSEA showed that different pathways and signaling pathways were involved between high and low risk groups,and immune correlation analysis suggested that the immune status was different between the high-risk group and the low-risk group.Conclusions:In this study,13 LUAD prognostic genes of ferroptosis-related lnc RNAs were screened out based on bioinformatics analysis.The risk model based on these 13 biomarkers can independently predict the prognosis of LUAD patients.In addition,the biological effects of ferroptosis-related lnc RNAs and LUAD were discussed through functional enrichment analysis,and the relationship between ferroptosis-related lnc RNAs and anti-tumor immunity was studied through GSEA and immune correlation analysis.