Molecular identification of an immunity- and Ferroptosis-related gene signature in non-small cell lung Cancer

Background Lung cancer is one of the dominant causes of cancer-related deaths worldwide. Ferroptosis, an iron-dependent form of programmed cell death, plays a key role in cancer immunotherapy. However, the role of immunity- and ferroptosis-related gene signatures in non-small cell lung cancer (NSCLC) remain unclear. Methods RNA-seq data and clinical information pertaining to NSCLC were collected from The Cancer Genome Atlas dataset. Univariate and multivariate Cox regression analyses were performed to identify ferroptosis-related genes. A receiver operating characteristic (ROC) model was established for sensitivity and specificity evaluation. Gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed to explore the function roles of differentially expressed genes. Results A signature composed of five ferroptosis-related genes was established to stratify patients into high- and low-risk subgroups. In comparison with patients in the low-risk group, those in the high-risk one showed significantly poor overall survival in the training and validation cohorts (P < 0.05). Multivariate Cox regression analysis indicated risk score to be an independent predictor of overall survival (P < 0.01). Further, the 1-, 2-, and 3-year ROCs were 0.623 vs. 0.792 vs. 0.635, 0.644 vs. 0.792 vs. 0.634, and 0.631 vs. 0.641 vs. 0.666 in one training and two validation cohorts, respectively. Functional analysis revealed that immune-related pathways were enriched and associated with abnormal activation of immune cells. Conclusions We identified five immunity- and ferroptosis-related genes that may be involved in NSCLC progression and prognosis. Targeting ferroptosis-related genes seems to be an alternative to clinical therapy for NSCLC.

Automated summary

Through the analysis of ferroptosis-related genes, we established a signature with five genes to stratify NSCLC patients into high-risk and low-risk subgroups. Patients in the high-risk group had significantly lower overall survival, and the risk score was an independent predictor of prognosis. Functional analysis revealed enrichment of immune-related pathways associated with abnormal activation of immune cells.