High ROBO3 expression predicts poor survival in non-M3 acute myeloid leukemia

Abstract

Roundabout guidance receptor proteins are crucial components of the SLIT/ROBO signaling pathway. This pathway is important for the nervous system and in embryonic development. Recently, increasing evidence has shown that roundabout guidance receptor proteins and the SLIT/ROBO signaling pathway also participate in tumorigenesis. Here, by analyzing transcriptome data from the TCGA and GEO databases, we found that ROBO3 is highly expressed in non-M3 acute myeloid leukemia. High ROBO3 expression was associated with increased age at diagnosis and poorer risk classification (both P < 0.01). Patients with high ROBO3 expression had higher rates of TP53 and RUNX1 mutations (both P < 0.05). Significantly worse overall survival and event-free survival were observed in high ROBO3 expression patients compared with low ROBO3 expression patients (OS: P = 0.004; EFS: P= 0.012). High ROBO3 expression was also associated with poorer overall survival and event-free survival in a subgroup of patients who received intensive chemotherapy (OS: P = 0.024; EFS: P = 0.040). Moreover, multivariate analysis indicated that high ROBO3 expression was an independent risk factor for poor overall survival in non-M3 acute myeloid leukemia patients who are younger than 60 and received intensive chemotherapy during remission induction. Bioinformatics analysis by Kyoto Encyclopedia of Genes and Genomes and Gene Ontology revealed that high ROBO3 expression significantly altered cell adhesion and extracellular matrix-related pathways (adjusted P < 0.05). Taken together, the data demonstrate that ROBO3 is upregulated in non-M3 acute myeloid leukemia and may be a potent biomarker of inferior prognosis.

SpinTip: A Simple, Robust, and Versatile Preanalytical Method for Microscale Suspension Cell Proteomics

“…SLIT/ROBO, a ligand/ receptor family first identified in neuronal guidance, 52 appears to be involved in AML biology, 53 and increased pathway activity may constitute a risk factor for poor survival. 54 However, it has not yet been linked to daunorubicin treatment response in AML patients. Neddylation, a ubiquitin-like posttranslational protein modification, is required for cancer cell growth and survival.…”

“…Our data from this proof-of-concept ex vivo study of a single AML patient uncovered previously identified pathways modulated by daunorubicin − and implicates the neddylation and SLIT/ROBO pathways as possible new targets for cotreatment with daunorubicine. SLIT/ROBO, a ligand/receptor family first identified in neuronal guidance, appears to be involved in AML biology, and increased pathway activity may constitute a risk factor for poor survival . However, it has not yet been linked to daunorubicin treatment response in AML patients.…”

ROBO3 is a Potential Prognostic Biomarker that guides treatment option and Correlates with Immune Cell Infiltration in Acute Myeloid Leukemia

“…Previous study had demonstrated that ROBO3 was overexpressed in AML and associated with poor prognosis (Cai et al, 2021, Gołos et al, 2019, but it did not distinguish the therapeutic outcome of chemotherapy and allo-HSCT based on ROBO3 expression. As we all know, the prognostic value of a biomarker is treatment-dependent in AML.…”