Analyzing the key gene expression and prognostics values for acute myeloid leukemia

Acute myeloid leukemia (AML) is one of the first tumor types sequenced at the whole genome level. However, numbers of the mutated genes expression levels, functions, and prognostics values still unclear.

To most ordinary mutated genes were analyzed via cancer virtual cohort discovery analysis platform (CVCDAP), and further investigated the mutational conversions, variant allele frequencies (VAF), driver genes, and potential druggable mutated genes in AML. The top mutated gene mRNA expression levels and the relationship between gene expression levels and prognosis for AML patients were performed by Gene Expression Profiling Interactive Analysis (GEPIA). Moreover, we used the UALCAN dataset to confirm the association between gene expression levels and prognosis for AML patients. Enrichment functions of the top mutated genes of AML were analyzed through Metascape. Finally, the role of these defined genes in cancer pathways and potential drug targets were analyzed by gene set cancer analysis (GSCALite).

The top 20 mutated genes for AML included FLT3, HPS3, ABCA6, PCLO, SLIT2, and other ones. Compared to normal control samples, NPM1 and GABRB3 were significantly downregulated in AML samples, but TP53, DNMT3A, HPS3, FLT3, SENP6, and RUNX1 were significantly overexpressed (all these genes P value <0.01). Overexpression of FLT3 and PCLO indicated a poor prognosis, but the overexpression of SLIT3 functioned as a protector for AML via GEPIA. HSP3 indicates the favorable factor for AML, but overexpression of ABCA6 (P=0.066) may act as the adverse factor by UALCAN analysis. Enrichment function analysis shows the functions of defining genes, including negative regulation of cell differentiation, small GTPase mediated signal transduction, and immune system process. Finally, these genes participate in apoptosis, cell cycle, PI3K/AKT, and RAS/MAPK signaling pathway, and FLT3 is sensitive to 5-Fluorouracil, Methotrexate, ATRA. DNMT3A and IDH2 are resistant to Trametinib. RUNX1 and TP53 were sensitive to I-BET-762 and Tubastatin A.

Present study showed overexpression of FLT3, ABCA6, and PCLO indicated the poor prognosis of AML, but overexpression of SLIT3 and HSP3 functioned as an AML protector. There are several drugs and small molecules that target the top 20 mutated genes in AML.