A prognostic model based on ferroptosis-related long non-coding RNA signatures and immunotherapy responses for non-small cell lung cancer.

Abstract

Non-small cell lung cancer (NSCLC) ranks high in the incidence of malignant tumors, with limited treatment options and poor prognosis. Ferroptosis is a newly discovered cell death mechanism based on iron and reactive oxygen species (ROS). The role of ferroptosis-related long non-coding RNAs (lncRNAs) and associated prognostic mechanisms in NSCLC require investigation. We constructed a prognostic multi-lncRNA signature based on ferroptosis-related differentially expressed lncRNAs in NSCLC. The levels of ferroptosis-related lncRNA in normal lung cells and lung adenocarcinoma cells were verified by RT-PCR. We identified eight differentially expressed lncRNAs associated with NSCLC prognosis. The expression of AC125807.2, AL365181.3, AL606489.1, LINC02320, and AC099850.3 was upregulated, while SALRNA1, AC026355.1, and AP002360.1 were downregulated in NSCLC cell lines. Kaplan-Meier analysis showed that a high-risk patient group was associated with poor NSCLC prognosis. A risk assessment model based on ferroptosis-related lncRNAs was superior to NSCLC prognosis based on traditional clinicopathological features. Gene Set Enrichment Analysis (GSEA) identified immune- and tumor-related pathways in low-risk group patients. In addition, The Cancer Genome Atlas (TCGA) showed that T cell function during APC co-inhibition, APC co-stimulation, chemokine receptor (CCR), MHC class I, parainflammation, T cell co-inhibition, and check-point expression differed significantly between low- and high-risk groups. M6A-related mRNA comparisons between these groups also revealed significant differences in ZC3H13, RBM15, and METTL3 expression. Our new model of lncRNA-associated ferroptosis effectively predicted NSCLC prognoses.