Abstract
Ferroptosis is closely linked to various cancers, including lung adenocarcinoma (LUAD); however, the factors involved in the regulation of ferroptosis-related genes are not well established. In this study, we identified and characterized ferroptosis-related long noncoding RNAs (lncRNAs) in LUAD. In particular, a coexpression network of ferroptosis-related mRNAs and lncRNAs from The Cancer Genome Atlas (TCGA) was constructed. Univariate and multivariate Cox proportional hazards analyses were performed to establish a prognostic ferroptosis-related lncRNA signature (FerRLSig). We obtained a prognostic risk model consisting of 10 ferroptosis-related lncRNAs: AL606489.1, AC106047.1, LINC02081, AC090559.1, AC026355.1, FAM83A-AS1, AL034397.3, AC092171.5, AC010980.2, and AC123595.1. High risk scores according to the FerRLSig were significantly associated with poor overall survival (hazard ratio (HR) = 1.412, 95% CI = 1.271–1.568; P < 0.001). Receiver operating characteristic (ROC) curves and a principal component analysis further supported the accuracy of the model. Next, a prognostic nomogram combining FerRLSig with clinical features was established and showed favorable predictive efficacy for survival risk stratification. In addition, gene set enrichment analysis (GSEA) revealed that FerRLSig is involved in many malignancy-associated immunoregulatory pathways. Based on the risk model, we found that the immune status and response to immunotherapy, chemotherapy, and targeted therapy differed significantly between the high-risk and low-risk groups. These results offer novel insights into the pathogenesis of LUAD, including the contribution of ferroptosis-related lncRNAs, and reveal a prognostic indicator with the potential to inform immunological research and treatment.
Highlights
Lung cancer is one of the leading causes of cancer-related deaths worldwide [1, 2]
1621 ferroptosis-related long noncoding RNAs (lncRNAs) were identified by Pearson correlation analysis (|R2 | > 0.3, P < 0.001)
21 lncRNAs whose expression levels were correlated with patient outcomes, suggesting that they had prognostic value for lung adenocarcinoma (LUAD), were screened by univariate Cox regression (P < 0.01, Fig. 1A, Table S2)
Summary
Lung cancer is one of the leading causes of cancer-related deaths worldwide [1, 2]. Integrative therapies such as molecular targeted therapy, chemotherapy, and radiotherapy have been developed for lung adenocarcinoma (LUAD), the 5-year overall survival (OS) rate is only 15% [3, 4]. Ferroptosis is a newly identified type of programmed cell death that is distinguished from apoptosis, necrosis, pyroptosis, and autophagic cell death [5, 6]. It induces cell injury or death via the iron-dependent lipid peroxidation process [7,8,9]. Its precise roles in the origin and progression of LUAD remain unclear
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