Bioinformatics-based identification of ferroptosis-related biomarkers and immune infiltration in retinoblastoma

Retinoblastoma (RB) is one of the most common primary intraocular malignancies in children. Its pathogenesis involves multiple signaling pathways that remain incompletely understood, and effective treatment strategies are still limited. This study aims to identify ferroptosis-related biomarkers and explore their roles in immune infiltration and therapeutic response in RB using bioinformatics approaches.

To investigate the role of ferroptosis in RB, we analyzed the microarray dataset GSE166173 to identify differentially expressed genes (DEGs) between healthy controls and RB patients. Ferroptosis-related DEGs were further screened, and least absolute shrinkage and selection operator (LASSO) regression was applied to identify candidate genes at the intersection of RB and ferroptosis. Key genes were subsequently examined by gene set enrichment analysis (GSEA), gene set variation analysis (GSVA), immune infiltration analysis, and drug sensitivity prediction.

Three ferroptosis-associated genes-NFE2L2, HSPB1, and JUN-were identified as potential diagnostic biomarkers for RB. Immune infiltration analysis revealed their potential roles in shaping the tumor immune microenvironment. Drug sensitivity analysis suggested AUY922, AG.014699, and AMG.706 as candidate therapeutic agents. Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) validation confirmed significant downregulation of JUN, HSPB1, and NFE2L2 in RB Y79 cells compared with retinal pigment epithelial (RPE) cells.

This study identified three ferroptosis-related genes (FRGs) as potential diagnostic biomarkers of RB. Their association with immune cell infiltration provides new insights into the molecular mechanisms of RB and highlights potential therapeutic opportunities.