Abstract
BackgroundLong non-coding RNAs (lncRNAs) are increasingly recognized as the crucial mediators in the regulation of ferroptosis and iron metabolism. A systematic understanding of ferroptosis and iron-metabolism related lncRNAs (FIRLs) in lung adenocarcinoma (LUAD) is essential for new diagnostic and therapeutic strategies.MethodsFIRLs were obtained through Pearson correlation analysis between ferroptosis and iron-metabolism related genes and all lncRNAs. Univariate and multivariate Cox regression analysis were used to identify optimal prognostic lncRNAs. Next, a novel signature was constructed and risk score of each patient was calculated. Survival analysis and ROC analysis were performed to evaluate the predictive performance using The Cancer Genome Atlas Lung Adenocarcinoma (TCGA-LUAD) and Gene Expression Omnibus (GEO) datasets, respectively. Furthermore, multivariate Cox and stratification analysis were used to assess prognostic value of this signature in whole cohort and various subgroups. The correlation of risk signature with immune infiltration and gene mutation was also discussed. The expression of lncRNAs was verified by quantitative real-time PCR (qRT-PCR).ResultsA 7-FIRLs signature including ARHGEF26-AS1, LINC01137, C20orf197, MGC32805, TMPO-AS1, LINC00324, and LINC01116 was established in the present study to assess the overall survival (OS) of LUAD. The survival analysis and ROC curve indicated good predictive performance of the signature in both the TCGA training set and the GEO validation set. Multivariate Cox and stratification analysis indicated that the 7‐FIRLs signature was an independent prognostic factor for OS. Nomogram exhibited robust validity in prognostic prediction. Differences in immune cells, immune functions and gene mutation were also found between high-risk and low-risk groups.ConclusionsThis risk signature based on the FIRLs may be promising for the clinical prediction of prognosis and immunotherapeutic responses in LUAD patients.
Highlights
Long non-coding RNAs are increasingly recognized as the crucial mediators in the regulation of ferroptosis and iron metabolism
14,142 Long non-coding RNAs (lncRNAs) were identified in the TCGA-lung adenocarcinoma (LUAD) and 1632 lncRNAs were identified in the GSE37745 according to the lncRNA annotation file
These lncRNAs were subjected to Pearson correlation analysis with 296 ferroptosis and iron metabolism related genes (Additional file 1: Figure S1A, B; |Correlation Coefficient| > 0.3 and p < 0.001)
Summary
Long non-coding RNAs (lncRNAs) are increasingly recognized as the crucial mediators in the regulation of ferroptosis and iron metabolism. A systematic understanding of ferroptosis and iron-metabolism related lncRNAs (FIRLs) in lung adenocarcinoma (LUAD) is essential for new diagnostic and therapeutic strategies. Ferroptosis has been identified as a potential prevention or therapeutic strategies to trigger cancer cell death, especially for malignancies that are resistant to traditional treatments [20]. Some studies have noticed the potential function of ferroptosis and iron metabolism in lung cancer development and suppression, but the detailed regulators remain unclear. LncRNAs have been shown to function as master regulators in various disease processes including cancer [11]. It has been found that lncRNAs are the crucial mediators in the regulation of ferroptosis and iron metabolism in cancer [33].
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