Identification and validation of an individualized prognostic signature of lung squamous cell carcinoma based on ferroptosis-related genes

Background: Lung squamous cell carcinoma (LUSC), one of the main pathological types of lung cancer, has led to consequential socioeconomic burden. Ferroptosis is an iron-dependent form of cell death process with potentials for therapeutic target in various kinds of tumors. However, whether ferroptosis-related genes (FRGs) are associated with the prognosis of LUSC patients is still unclear. The aim of this study was to establish a FRGs-based signature which could stratify patients with LUSC. Methods: The RNA sequencing profiles and corresponding clinical data of LUSC patients were retrieved from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) dataset. A FRG-based signature was developed using the TCGA-LUSC cohort and validated in the GEO cohort. Gene set enrichment analysis (GSEA) and analysis of immune cell characteristics were conducted to assess the relationship between FRGs and biological function or immune status. A nomogram based on selected clinical factors and the risk scores which were generated from the FRG-based signature was developed using the TCGA cohort and validated in the GEO cohort. Results: A set of 16 FRGs, significantly associated with overall survival (OS) in the TCGA cohort, was identified and could classify LUSC patients into two risk groups. Kaplan-Meier analysis illustrated that the survival rate of the high-risk group was significantly lower than the low-risk group. Assessment and external validation of the signature showed that the survival predictive performance of this signature was adequate. Additionally, multiple pathways and functions were enriched through GSEA and the analysis of immune cell characteristics showed significantly different abundances of immune cells among the two risk groups. Finally, a nomogram integrating the FRG-based signature and selected clinical factors was also developed and assessed in both the TCGA and GEO cohort. Conclusion: This study indicated the association between the FRGs and prognosis of patients with LUSC. Targeting ferroptosis may serve as a novel potential therapeutic alternative for LUSC. Keywords: ferroptosis; lung squamous cell carcinoma; overall survival; prognostic signature.