Prognostic significance of ferroptosis-related genes and their methylation in AML

Abstract

Background: Ferroptosis involves in the development and therapeutic response of various types of tumors. This study aims to explore ferroptosis-related prognostic genes that could further accurately stratify AML patients. Methods: We investigated the prognosis significance of ferroptosis-related genes in AML by Univariate and multivariate Cox proportional hazards regression analyses. With the methylation data of TCGA samples, we looked for methylation sites associated with prognostic genes and compared the correlation between methylation and mRNA expression. R software and ‘edgeR’ packages were used to identify the DEGs between the high-and-low-risk groups divided by the FRPGs prognosis model and then run GO enrichment, KEGG pathway, and PPI network. Results: We found a prognostic risk model that included AKR1C2 and SOCS1 predicted outcomes in AML patients. Methylation analysis showed that AKR1C2 and SOCS1 are negatively regulated by their methylation, leading to their low expression in AML patients. Besides, both decreased SOCS1 expression and hypermethylation predicted favorable OS and PFS in AML patients. Finally, this prognostic risk model exhibited a close correlation with several clinical features, especially with age (P=0.005), cytogenetic type (P=0.031), risk_cytogenetic (P=0.001), and risk_molecular (P<0.001). Functional enrichment analysis showed that DEGs are most enriched in the regulation of cell death and the PI3K-Akt signaling pathway. Conclusion: AKR1C2 and SOCS1 are promising biomarkers for predicting prognosis in patients with AML.