Novel ferroptosis-related gene signature as a potential prognostic tool for gastric cancer

Abstract

Objectives Gastric cancer (GC) is a major global health concern and is difficult to diagnose in the early stage. Ferroptosis is an iron-dependent, novel form of non-apoptotic cell death. In recent years, inducing the upregulation of ferroptosis-related genes has become a promising therapeutic alternative for cancers, especially those resistant to traditional treatments. However, the relationship between ferroptosis-related genes and GC remains to be further elucidated. Methods In the present study, mRNA expression profiles and corresponding clinical data of patients with GC were retrieved from The Cancer Genome Atlas and used as test data. A multigene signature was constructed using the least absolute shrinkage and selection operator Cox regression model. Data of patients with GC from ‘GSE84426’ in the Gene Expression Omnibus database were used as Training data for validation. Results More than half ferroptosis-related genes were differentially expressed in GC tissues and adjacent normal tissue samples (58.43%) in the test data. Univariate Cox regression analysis showed that 16 differentially expressed genes were related to the prognosis of GC (all p < 0.05). Expression profiles of the 16 DGEs were analysed using LASSO Cox regression, and a prognostic model was established by selecting the 10 best genes for λ. These 10 genes were used to construct a 10-gene signature and stratify patients into two risk groups. Based on the median risk score in the test data, patients with GC were divided into high- and low-risk groups ( p < 0.001). Risk score was an independent predictor for overall survival in multivariate Cox regression analyses ( p < 0.001 and <0.01 in the test and training data, respectively; hazard ratio >1). Receiver operating characteristic curve analysis confirmed the predictive capacity of the 10-gene signature. Functional analysis revealed that tumour-infiltrating lymphocytes, antigen-presenting cell co-stimulation, and cytokine-cytokine receptors were enriched; however, the immune status differed between the two risk groups. Conclusion The novel ferroptosis-related gene signature can be used for GC prognosis. In addition, ferroptosis may provide a novel alternative for the diagnosis and treatment of GC.