Construction and Validation of a CNV-Driven Ferroptosis-Related Gene Signature for Predicting the Prognosis of Lung Adenocarcinoma

Abstract

Background. Previous studies have shown that ferroptosis plays an integral role in the development of cancer and copy number variations (CNVs) have been reported to associated with the ferroptosis. However, the role of CNVs-driven ferroptosis-related genes (FRGs) in lung adenocarcinoma (LUAD) continues to be poorly understood. Therefore, we aimed to establish a novel gene signature in LUAD based on CNVs-driven ferroptosis-related genes. Methods. The transcriptome data and clinical features of LUAD patients were downloaded from the Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database. Differential analysis was carried out to recognize differentially expressed CNV-driven FRGs. Univariate Cox and least absolute shrinkage and selection operator (LASSO) regression analyses were utilized to identify prognosis-associated genes. Kaplan-Meier (K-M) analysis was a builder to estimate the worth of model. In addition, the nomogram was created to estimate survival probability of each patient. Ultimately, the immune microenvironment landscape between high and low risk groups was evaluated. Results. A total of 22 differentially expressed CNV-driven FRGs were acquired in LUAD. These genes were significantly associated with serine family amino acid metabolism, iron regulation, reactive oxygen species metabolism, and cellular response to oxidative stress, and were involved in amino acid metabolism, malaria, amino acid biosynthesis, and HIF-1 signaling pathways. Moreover, on the strength of 6 genes (TFAP2A, SLC2A1, AURKA, CDO1, SLC7A11, and ALOX5), the prognostic model was created, and the LUAD samples were significantly fall into the high- and low-risk groups, with the high-risk group had a poorer prognosis. Furthermore, risk score was an independent prognostic element. The nomogram with excellent predictive performance was developed for calculating the final result of LUAD patients at 1, 2, and 3 years. Finally, 19 immune cells had different infiltration differences among groups. Conclusion. A novel CNV-driven ferroptosis-related prognosis was established and could be used as a predictive indicator in LUAD. However, further clinical and in vivo in vitro experiments are necessary.