Risk stratification of lung adenocarcinoma using a nomogram combined with ferroptosis-related LncRNAs and subgroup analysis with immune and N6-methyladenosine modification

Abstract

Background Determining the prognosis of lung adenocarcinoma (LUAD) is challenging. The present study aimed to identify prognostic ferroptosis-related long noncoding RNAs (FRLs) and construct a prognostic model. Moreover, differential analysis of immune and N6-methyladenosine (m6A)-related genes was systematically conducted. Methods A total of 504 patients selected from a dataset from The Cancer Genome Atlas were included. The patients with LUAD were randomly divided into a training group and a test group at a ratio of 1:1. Pearson correlation analysis and univariate Cox regression analysis were used to identify the prognostic FRLs. Then, a prognostic model was constructed from the optimized subset of prognostic FRLs based on the least absolute shrinkage and selection operator (LASSO) algorithm. Subsequently, the receiver operating characteristic (ROC) curve and survival analysis were used to evaluate the performance of the model. The risk score based on the prognostic model was analyzed using Cox regression analysis. Moreover, gene set enrichment analysis and differential analysis of immune- and m6A-related genes were conducted. Results After univariate Cox regression analysis and LASSO algorithm analysis, a total of 19 prognostic FRLs were selected to construct the final model to obtain the risk score. The area under the ROC curve of the prognostic model for 1-year, 3-year, and 5-year overall survival (OS) was 0.763, 0.745, and 0.778 in the training set and 0.716, 0.724, and 0.736 in the validation set, respectively. Moreover, the OS of the high-risk group was significantly worse than that of the low-risk group in the training group (P < 0.001) and in the test group (P < 0.001). After univariate and multivariate Cox regression analysis, the risk score [hazard ratio (HR) = 1.734; P < 0.001] and stage (HR = 1.557; P < 0.001) were both considered significant prognostic factors for LUAD. A nomogram was constructed based on clinical features and risk score. The expression of 34 checkpoint genes and 13 m6A-related genes varied significantly between the two risk groups. Conclusion This study constructed a prognostic model to effectively predict the OS of patients with LUAD, and these OS-related FRLs might serve as potential therapeutic targets of LUAD.

Characterization and validation of a ferroptosis-related LncRNA signature as a novel prognostic model for lung adenocarcinoma in tumor microenvironment

“…To highlight the superiority of our model, we compared the published literature on ferroptosis-related lncRNAs, among which Gao et al. ( 32 ), Guo et al. ( 33 ), Fei et al.…”

Prognostic Model Establishment and Immune Microenvironment Analysis of Lung Adenocarcinoma Based on Ferroptosis-Related Long Noncoding RNAs

“…Latest research has con rmed that FRLs can affect the occurrence and development of various cancers [9][10][11][12][13]. Relevant regulatory patterns have also been found in lung cancer [31]. However, there are still few studies on the relevant mechanisms.…”

Regulation of Ferroptosis in Lung Adenocarcinoma

“…In addition, bioinformatics analyses have revealed a potential clinical connection between the FRGs and LUAD patients. A prognostic model integrating several FRGs was used to predict the prognosis, mutation burden, tumor microenvironment (TME) cell infiltration characteristics, immunotherapy effects, and chemotherapy sensitivities in patients with LUAD [32][33][34][35][36][37].…”