Abstract
Introduction: Ferroptosis offers novel perspectives for treating multiple blood-related diseases, yet its role in aplastic anaemia (AA) is rare. This study aimed to explore key ferroptosis-related genes (FRGs) in AA using bulk and single-cell RNA sequencing (scRNA-seq) data. Methods: scRNA-seq and bulk RNA-seq data, along with FRG lists, were obtained from public databases. Differentially expressed FRGs (DEFRGs) between AA and control samples were identified, followed by functional enrichment and protein–protein interaction analyses. Single-cell analyses were conducted to reveal main cell types in samples and DEFRGs activity in each cell was assessed. Moreover, DEGs between AA and control samples at the cellular level were explored, followed by integration with DEFRGs to determine common key genes. KEGG pathway analysis of these genes was performed at the cellular level. Immune infiltration analysis was used to evaluate the relationship between key genes and immune cells. Results: A total of 38 DEFRGs were identified, enriched in pathways such as the intrinsic apoptotic signalling pathway. scRNA-seq analysis identified seven cell types, with elevated DEFRGs activity in platelets and stromal cells. Key genes DDIT4 and NCF2, identified through integrated analysis, were involved in autophagy, mTOR signalling, and osteoclast differentiation pathways. Moreover, their expressions were positively correlated with activated dendritic cells in AA samples. Conclusion: Our findings highlight the roles of DDIT4 and NCF2, in AA progression, providing potential insights for further mechanistic exploration of AA.
Plain Language Summary
Aplastic anaemia (AA) is a rare haemopoietic stem-cell disorder that results in a poor prognosis and low survival rate for patients. Conventional treatments have improved the prognosis of patients to some extent, but there are significant limitations. Ferroptosis is a type of iron-dependent programmed cell death, and key ferroptosis-related genes (FRGs) have been shown to be associated with AA, but fewer studies have been based on this to identify AA-related biomarkers. In this study, we screened a total of 38 DEFRGs in AA and control samples using the Gene Expression Omnibus (GEO) database, which were mainly clustered in functions such as the intrinsic apoptotic signalling pathway. Further analysis by single-cell RNA revealed that there were seven cell types in AA. In addition, immune infiltration analysis showed that activated dendritic cells were significantly associated with these two key genes. In summary, this study highlights the critical role of FRGs, especially DDIT4 and NCF2, in the progression of AA and provides a theoretical basis for the clinical management of AA.
