Abstract
BackgroundNon-small cell lung cancer (NSCLC) is the most prevalent type of lung carcinoma with an unfavorable prognosis. Ferroptosis is involved in the development of multiple cancers. Whereas, the prognostic value of ferroptosis-related lncRNAs in NSCLC remains uncertain.MethodsGene expression profiles and clinical information of NSCLC were retrieved from the TCGA database. Ferroptosis-related genes (FRGs) were explored in the FerrDb database and previous studies, ferroptosis-related lncRNAs (FRGs-lncRNAs) were identified by the correlation analysis and the LncTarD database. The differentially expressed FRGs-lncRNAs were screened and FRGs-lncRNAs associated with the prognosis were explored by univariate Cox regression analysis and Kaplan–Meier survival analysis. Then, an FRGs-lncRNAs signature was constructed and verified by the Lasso-penalized Cox analysis. Finally, the potential correlation between risk score, immune checkpoint genes, and chemotherapeutic sensitivity was further investigated.Results129 lncRNAs with a potential regulatory relationship with 59 differentially expressed FRGs were found in NSCLC, of which 10 were related to the prognosis of NSCLC (P < 0.05). 9 prognostic-related FRGs-lncRNAs were used to construct the prognostic model and stratify NSCLC patients into high- and low-risk groups. A worse outcome was found in patients with high risk (P < 0.05). Moreover, a good predictive capacity of this signature in predicting NSCLC prognosis was confirmed. Additionally, 45 immune checkpoint genes and 4 chemotherapeutics drugs for NSCLC were identified to be correlated with the risk score.ConclusionA novel FRGs-lncRNAs signature was successfully constructed, which may contribute to improving the management strategies of NSCLC.
Highlights
Lung cancer ranks top in the incidence of malignancies and imposes an enormous socio-economic burden worldwide [1]
Several studies have constructed some prognostic signatures in many cancers, including LUAD [16], head and neck squamous cell carcinoma [17], bladder [18], and colon cancer [19], by exploring the prognostic ferroptosis-related Long non-coding RNAs (lncRNAs) to assist clinicians to evaluate the prognosis of patients
Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that these DE-Ferroptosis-related genes (FRGs) participate in ferroptosis, arachidonic acid metabolism, glutathione metabolism, and NOD-like receptor signaling pathway (Fig. 3B)
Summary
Lung cancer ranks top in the incidence of malignancies and imposes an enormous socio-economic burden worldwide [1]. Li et al BMC Medical Genomics (2021) 14:286 in the targeted therapy and immunotherapy of lung cancer, the long-time survival rate of NSCLC remains unsatisfactory [4,5,6], and most patients will inevitably develop drug resistance. Since most anti-tumor drugs play a therapeutic role by inducing apoptosis of cancer cells, it is of great significance to pinpoint novel cell death pathways in NSCLC and discover new directions for identifying treatment strategies and evaluating prognosis. Several studies have constructed some prognostic signatures in many cancers, including LUAD [16], head and neck squamous cell carcinoma [17], bladder [18], and colon cancer [19], by exploring the prognostic ferroptosis-related lncRNAs to assist clinicians to evaluate the prognosis of patients. Non-small cell lung cancer (NSCLC) is the most prevalent type of lung carcinoma with an unfavorable prognosis. The prognostic value of ferroptosis-related lncRNAs in NSCLC remains uncertain
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