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

OBJECTIVE: Non-small cell lung cancer (NSCLC) ranks high in the incidence of malignant tumors, with limited treatment op-tions 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 (ln-cRNAs) and associated prognostic mechanisms in NSCLC require investigation.MATERIALS AND METHODS: We construct-ed a prognostic multi-lncRNA signature based on ferroptosis-related differentially expressed lncRNAs in NSCLC. The levels of ferroptosis-re-lated lncRNA in normal lung cells and lung ade-nocarcinoma cells were verified by RT-PCR.RESULTS: We identified eight differentially ex-pressed lncRNAs associated with NSCLC prog-nosis. 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 NS-CLC prognosis. A risk assessment model based on ferroptosis-related lncRNAs was superior to NSCLC prognosis based on traditional clinico-pathological features. Gene Set Enrichment Anal-ysis (GSEA) identified immune-and tumor -relat-ed pathways in low-risk group patients. In addi-tion, 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 significant-ly between low-and high-risk groups. M6A-re-lated mRNA comparisons between these groups also revealed significant differences in ZC3H13, RBM15, and METTL3 expression.CONCLUSIONS: Our new model of ln-cRNA-associated ferroptosis effectively predict-ed NSCLC prognoses.