Ferroptosis-related gene analysis revealing novel biomarkers and therapeutic targets in diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) is an aggressive, heterogeneous non-Hodgkin lymphoma with high relapse rates and drug resistance, which necessitates novel biomarkers. This study aimed to fill a research gap by investigating the function of ferroptosis-an iron-dependent form of programmed cell death-in DLBCL, an area that remains inadequately explored. Employing a comprehensive bioinformatics framework, we analyzed ferroptosis-related genes in The Cancer Genome Atlas-DLBCL dataset using consensus clustering and differential expression, somatic mutation, copy number variation (CNV), gene ontology and pathway enrichment, and immune infiltration analyses. Our analysis identified two DLBCL subtypes, revealing 912 differentially expressed genes, including 24 ferroptosis-related differentially expressed genes (FRDEGs). Enrichment analyses indicated that these genes are involved in crucial biological pathways, including the lipoxygenase pathway and inflammatory regulation, while immune infiltration assessment highlighted significant correlations with specific immune cell types, particularly the positive correlation of IDO1 with M1 macrophages and the negative correlation of IFNG with memory B cells. Further, we established a prognostic risk model incorporating CDKN1A, KLF2, and IFNG that holds promise for predicting patient outcomes. These findings demonstrate that ferroptosis regulates DLBCL progression and identify potential biomarkers/therapeutic targets requiring validation to develop new therapies.