THE ROLE OF SLC22A4 IN ACUTE MYELOID LEUKEMIA

Abstract

Objective: This study aimed to explore the role of SLC22A4 (encoding OCTN1, an organic cation transporter) in acute myeloid leukemia (AML) prognosis and therapy. Methods: We analyzed RNA-seq data from 151 TCGA-AML samples and six Gene Expression Omnibus (GEO) datasets (GSE9476, GSE12662, GSE30029, GSE34577, GSE12417, GSE37642), including 62 normal bone marrow samples and 520 AML samples. Weighted gene co-expression network analysis (WGCNA) 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 gene expression was significantly decreased in AML versus normal samples. The high-expression group was associated with better prognosis versus the low-expression group. Gene set enrichment analysis revealed enrichment of the metabolic transport and immune and tumor-related pathways. In addition, SLC22A4 expression was negatively correlated with immune cells (e.g., activated dendritic cells, CD8 T cells). Methylation of SLC22A4 was significantly negatively correlated with expression. Moreover, it was predicted that 5 miRNAs (i.e., hsa-miR-1299, hsa-miR-1910-5p, hsa-miR-3659, hsa-miR-5093, and hsa-miR-6831-3p) could regulate SLC22A4 gene expression. SLC22A4 expression was positively correlated with sensitivity to cyclobenzaprine, hydrochloride, SGX-523, and simvastatin. However, it was negatively correlated with sensitivity to fluorouracil, abexinostat, EMD-534085, hypothemycin, tamoxifen, and sunitinib. Conclusion: SLC22A4 may be useful as a predictor of poor prognosis and a marker of immunologic infiltration or potent molecular-targeted agents in AML.