Aml-013 a prospective study to evaluate the prognostic implications and molecular mechanism of slc40a1 gene in primary acute myeloid leukemia

Abstract

Context Acute myeloid leukemia (AML) is a genetically heterogeneous hematologic disorder characterized by abnormal myeloid progenitor cell proliferation and differentiation, often accompanied by genetic and epigenetic alterations. Iron metabolism is implicated in various cancers, yet its role in AML remains poorly understood. Ferroportin, encoded by the SLC40A1 gene, is vital for cellular iron export, but its significance and interactions in AML are unclear. Objective This study aimed to characterize the molecular functions, clinical relevance, and prognostic value of the SLC40A1 gene in AML. Methods We investigated SLC40A1 gene expression in AML (n=173) and control (n=70) cases, followed by correlation analysis to identify associated genes using the Linked Omics database. Prognostic significance was evaluated using Kaplan–Meier survival estimation. DNA methylation status was assessed using the MEXPRESS database. Molecular mechanisms were explored via gene set enrichment analysis (GSEA), and the relationship with immune checkpoints was studied using the SANGER Box 3.0 database. Results Laboratory Oncology Unit, Dr. B.R.A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences New Delhi, India SLC40A1 mRNA was significantly overexpressed in AML cohorts and correlated with poor overall survival (P<0.05). Positive correlations were found with DNAJC6, CD59, PLS1, GCLM, and CAPRIN2 genes, while negative correlations were observed with MSLN, MYH11, DAGLB, ST18, and PLCD3 (PCC <0.80). Lower methylation levels of SLC40A1 were observed in AML, inversely associated with gene expression. Gene enrichment analysis revealed enrichment in biologic processes such as lymphocyte homeostasis, endothelium development, spleen development, cell communication, and cell differentiation, while in molecular function SLC40A1 gene was enriched in iron ion transmembrane transporter, metal cluster binding, growth factor binding, and catalytic activity. KEGG pathway analysis implicated SLC40A1 in critical pathways like hematopoietic stem cell differentiation, ferroptosis, mRNA surveillance pathway, autophagy, TGF-beta signaling pathway, and signaling pathways regulating pluripotency of stem cells. Additionally, SLC40A1 positively correlated with immune checkpoints including CD160, CD274, CD40, CD44, and CD80. Conclusions SLC40A1 plays a significant role in AML progression and may serve as a potential prognostic biomarker and therapeutic target. This study provides insights into the molecular mechanisms underlying SLC40A1 involvement in AML pathogenesis, offering avenues for novel therapeutic interventions.