Rho-related BTB domain (RhoBTB) proteins belong to Rho guanosine triphosphatases (GTPases). Their putative role implicated in carcinogenesis has been supported by accumulating evidence. However, their expression pattern and potential role in acute myeloid leukemia (AML) remain unclear.

We profiled RHOBTB mRNA expression via the Gene Expression Profiling Interactive Analysis 2 (GEPIA2) database. Survival analysis was conducted with GEPIA2 and UALCAN. Univariate and multivariate Cox regression analyses were performed to validate RHOBTB genes as independent prognostic indicators in the LAML cohort from The Cancer Genome Atlas (TCGA). Data regarding expression in different subtypes and relationships with common disease-related genes were retrieved from UALCAN. Co-expressed genes were screened out and subsequently subjected to functional enrichment analysis.

We observed aberrant transcription levels of RHOBTB genes in AML patients. RHOBTB2 was identified as a prognostic candidate for overall survival (OS), independent of prognosis-related clinical factors and genetic abnormalities. Moreover, RHOBTB2 expression was increased in non-acute promyelocytic leukemia (APL) subtypes, patients without FLT3 mutation and PML/RAR fusion, and imparted a positive correlation with the expression of FLT3, FHL1, and RUNXs. Co-expressed genes of RHOBTB2 were enriched in functional pathways in AML.

Our findings suggest that RHOBTB2 might be a novel biomarker and independent prognostic indicator in AML and provide insights into the leukemogenesis and molecular network of AML.