836P - A prospective study to evaluate the prognostic implications and molecular mechanism of SLC40A1 gene in primary acute myeloid leukemia

Background

Acute myeloid leukemia (AML) is a diverse blood disorder marked by abnormal cell growth and differentiation, often involving genetic and epigenetic changes. Despite iron metabolism's known role in cancer, its involvement in AML remains unclear. Ferroportin, encoded by the SLC40A1 gene, is essential for iron export, yet its significance in AML is uncertain. This study aimed to elucidate the molecular functions, clinical relevance, and prognostic value of the SLC40A1 gene in AML.

Methods

In this study, we analyzed SLC40A1 gene expression in AML (n=173) and control (n=70) cases, identifying associated genes through correlation analysis with the Linked Omics database. Prognostic significance was determined using Kaplan–Meier survival estimation, while DNA methylation status was assessed with the MEXPRESS database. Molecular mechanisms were explored using gene set enrichment analysis (GSEA), and the relationship with immune checkpoints was investigated using the SANGER Box 3.0 database.

Results

SLC40A1 mRNA was significantly overexpressed in AML and associated 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. Lower methylation levels of SLC40A1 were observed in AML, inversely associated with gene expression. Gene enrichment analysis revealed involvement in biological processes such as lymphocyte homeostasis, endothelium development, spleen development, and cell differentiation. In terms of molecular function, SLC40A1 was enriched in iron ion transmembrane transporter activity, metal cluster binding, growth factor binding, and catalytic activity. KEGG pathway analysis implicated SLC40A1 in hematopoietic stem cell differentiation, ferroptosis, mRNA surveillance pathway, autophagy, and TGF-beta signaling pathway. Furthermore, SLC40A1 positively correlated with immune checkpoints 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.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.