One Ferroptosis-Related Gene-Pair Signature Serves as an Original Prognostic Biomarker in Lung Adenocarcinoma

Abstract

Lung adenocarcinoma is the most common histological subtype of lung cancer which causes the largest number of deaths worldwide. Exploring reliable prognostic biomarkers based on biological behaviors and molecular mechanisms is essential for predicting prognosis and individualized treatment strategies. Ferroptosis is a recently discovered type of regulated cell death. We downloaded ferroptosis-related genes from the literature and collected transcriptome profiles of lung adenocarcinoma from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) to construct ferroptosis-related gene-pair matrixes. Then, we performed the least absolute shrinkage and selection operator regression to build our prognostic ferroptosis-related gene-pair index (FRGPI) in TCGA training matrix. Our study validated FRGPI through ROC curves, Kaplan–Meier methods, and Cox hazard analyses in TCGA and GEO cohorts. The optimal cut-off 0.081 stratified patients into low- and high-FRGPI groups. Also, the low-FRGPI group had a significantly better prognosis than the high-FRGPI group. For further study, we analyzed differentially expressed ferroptosis-related genes between high- and low-FRGPI groups. Gene set enrichment analysis (GSEA) enrichment maps indicated that “cell cycle,” “DNA replication,” “proteasome,” and “the p53 signaling pathway” were significantly enriched in the high-FRGPI group. The high-FRGPI group also presented higher infiltration of M1 macrophages. Meanwhile, there were few differences in adaptive immune responses between high- and low-FRGPI groups. In conclusion, FRGPI was an independent prognostic biomarker which might be beneficial for guiding individualized tumor therapy.

Ferroptosis in lung cancer: dual role, multi-level regulation, and new therapeutic strategies

“…Thioredoxin-Interacting Protein shows a positive correlation with immune cell infiltration in SCLC, possibly serving as a biomarker for prognosticating treatment outcomes of chemotherapy and immunotherapy in SCLC patients. Li Lei and his team devised a Ferroptosis-Related Gene Pair Index, which may act as an independent prognostic biomarker for personalized tumor treatment ( 81 ). FANCD2, acting as a negative modulator of ferroptosis, can be an independent biomarker indicating unfavorable outcomes in LUAD patients ( 57 ).…”