High Expression of ARHGEF5 Predicts Unfavorable Prognosis in Acute Myeloid Leukemia

Acute myeloid leukemia (AML) represents a hematological neoplasm that is defined by high heterogeneity. Therefore, identifying new molecular markers for predicting the prognosis and optimizing therapeutic interventions for patients suffering from AML is crucial. Although an increase in Rho guanine nucleotide exchange factor 5 (ARHGEF5) expression level was observed in multiple cancer types, its involvement in AML remains unexplored. We obtained data on the gene expression of patients by accessing "the Cancer Genome Atlas (TCGA)" database to determine ARHGEF5 and AML correlation. Next, a Wilcoxon rank-sum test was conducted for comparing ARHGEF5 expression in patients with AML and normal samples. Additionally, we determined the correlation between ARHGEF5 and patient survival through the Kaplan-Meier (K-M) method as well as Cox regression analysis (CRA). Moreover, a nomogram was constructed using CRA for the prediction of the ARHGEF5 effect on patient prognosis. Next, we determined the pathway and function enriched by ARHGEF5-related genes as well as the association between ARHGEF5 and immune cells using the GO and KEGG pathway enrichment, protein-protein interaction network, and single sample gene set enrichment analyses. The findings indicate a significant ARHGEF5 overexpression in various cancers, including AML, compared to normal samples. Furthermore, the results demonstrated a significant association between ARHGEF5 overexpression and poor prognosis of 151 patients suffering from AML, patients with age ≤ 60, patients harboring mutations in NPM1, FLT3 mutation-positive, and patients harboring wild-type RAS ( P < 0.05). CRA showed that an increase in ARHGEF5 expression level could independently predict the patient's prognosis. The nomogram prognostic model was constructed by incorporating the age and cytogenetics risk of patients. Further, we identified 412 differentially expressed genes (DEGs) between the groups with high and low expression of ARHGEF5 . Specifically, 216 of these DEGs were observed to be overexpressed, while 196 were suppressed. ARHGEF5 overexpression could be a biomarker for predicting unfavorable outcomes among patients with AML. In addition, these DEGs and pathways could clarify the mechanisms behind AML onset and progression.