Abstract
BACKGROUND: This study aimed to explore the role of SLC22A4 (encoding the organic cation transporter OCTN1) in acute myeloid leukaemia (AML) prognosis and therapy. Methods: RNA-sequencing data from 151 TCGA-AML samples and six Gene Expression Omnibus datasets (62 normal bone marrow and 520 AML samples) were analysed. Weighted gene co-expression network analysis identified immune-related gene modules. Differential expression analysis, survival analysis (Kaplan-Meier, Cox regression), methylation profiling, immune infiltration (xCell, EPIC), and drug sensitivity correlations were performed. Statistical methods included Wilcoxon rank-sum tests, ROC curves, and LASSO regression. RESULTS: SLC22A4 expression was significantly decreased in AML compared with normal samples. The high-expression group was associated with a better prognosis than the low-expression group. Gene set enrichment analysis revealed enrichment in metabolic transport, immune, and tumour-related pathways. SLC22A4 expression was negatively correlated with immune cells, and methylation of SLC22A4 was significantly negatively correlated with expression. Moreover, it was predicted that 5 miRNAs could regulate SLC22A4 expression. Drug-sensitivity analysis showed positive correlations with cyclobenzaprine, hydrochloride, SGX-523, and simvastatin, and negative correlations with fluorouracil, abexinostat, EMD-534085, hypothemycin, tamoxifen, and sunitinib. CONCLUSION: SLC22A4 may be useful as a potent molecular-targeted agent in AML.