11P - 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 genetically diverse hematological disorder marked by abnormal differentiation and clonal proliferation of myeloid progenitor cells in the bone marrow, with various genetic and epigenetic alterations. Ferroportin, encoded by the SLC40A1 gene, is the sole protein responsible for cellular iron export. However, the expression, molecular mechanisms, and interactions of SLC40A1 in AML remain unclear. This study aims to elucidate the molecular functions, clinical, and prognostic value of SLC40A1 in AML.

Methods

We examined the expression level of SLC40A1 in AML (n=173) and control (n=70) samples. Correlation analysis was performed to identify genes potentially associated with SLC40A1 expression using the Linked Omics database. The DNA methylation status of SLC40A1 was evaluated using the MEXPRESS database. Gene set enrichment analysis (GSEA) was conducted to explore the molecular mechanisms of SLC40A1 in AML. The relationship between SLC40A1 expression and immune checkpoints was studied using the SANGER Box 3.0 database.

Results

SLC40A1 mRNA was significantly overexpressed in AML cohorts compared to normal samples and was associated with poor overall survival (P < 0.05). Correlation analysis revealed that SLC40A1 was positively correlated with DNAJC6, CD59, and CAPRIN2, and negatively correlated with MSLN, MYH11, and PLCD3 (PCC < 0.80). Lower methylation levels of SLC40A1 were observed in AML, which were negatively associated with its expression. Gene enrichment analysis showed SLC40A1 was involved in biological processes such as lymphocyte homeostasis, cell communication, and differentiation. In terms of molecular functions, SLC40A1 was enriched in iron ion transmembrane transporter activity, growth factor binding, and catalytic activity. KEGG pathway analysis indicated enrichment in hematopoietic stem cell differentiation, TGF-beta signaling, and pathways regulating pluripotency of stem cells. Additionally, SLC40A1 expression was positively correlated with immune checkpoints including CD40, CD44, and CD80.

Conclusions

SLC40A1 may serve as a potential prognostic biomarker and therapeutic target for effective AML management.

Clinical trial identification

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.