Identification of the Ferroptosis-Related Long Non-Coding RNAs Signature to Improve the Prognosis Prediction in patients with NSCLC

Abstract Background: Non-small cell lung cancer (NSCLC) is the most prevalent type of lung carcinoma with an unfavorable prognosis. Ferroptosis, a novel iron-dependent programmed cell death, is involved in the development of multiple cancers. Of note, the prognostic value of ferroptosis-related lncRNAs in NSCLC remains uncertain. Methods: Gene expression profiles and clinical information of NSCLC were retrieved from the TCGA database. Ferroptosis-related genes (FRGs) were explored in the FerrDb database and ferroptosis-related lncRNAs (FRGs-lncRNAs) were identified by the correlation analysis and the LncTarD database. Next, 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 by the Lasso-penalized Cox model in the training cohort and verified by internal and external validation. Finally, the potential correlation between risk score, immune response, and chemotherapeutic sensitivity was further investigated.Results: 129 lncRNAs with a potential regulatory relationship with 59 differentially expressed FRGs were found in NSCLC and 10 FRGs-lncRNAs associated with the prognosis of NSCLC were identified (P<0.05). 9 prognostic-related FRGs-lncRNAs (AQP4-AS1, DANCR, LINC00460, LINC00892, LINC00996, MED4-AS1, SNHG7, UCA1, and WWC2-AS2) were used to construct the prognostic model and stratify patients with NSCLC into high- and low-risk groups. Kaplan-Meier analysis demonstrated a worse outcome in patients with high risk (P<0.05). Moreover, a good predictive capacity of this signature in predicting NSCLC prognosis was confirmed by the ROC curve analysis. Additionally, 45 immune checkpoint genes and 8 m6A-related genes were found differentially expressed in the two risk groups, and the sensitivity of 28 chemotherapeutics were identified to be correlated with the risk score. Conclusion: A novel FRGs-lncRNAs signature was successfully constructed, which may contribute to improving the management strategies of NSCLC.