High ROBO3 expression predicts poor survival in non-M3 acute myeloid leukemia
Zhimei Cai1,2, Jifeng Wei1,2, Ze Chen1,2
1Department of Hematology, The Affiliated Lianyungang Hospital of Xuzhou Medical University/The First People's Hospital of Lianyungang, Lianyungang 222002, China.
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.
Insights
Roundabout guidance receptor 3 (ROBO3) is upregulated in non-M3 acute myeloid leukemia, correlating with poorer prognosis. High ROBO3 expression indicates a higher risk of adverse outcomes and specific mutations, suggesting its potential as a prognostic biomarker.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The SLIT/ROBO signaling pathway, involving roundabout guidance receptor proteins, is critical for nervous system development.
- Emerging evidence implicates this pathway in tumorigenesis.
- The specific role of ROBO3 in acute myeloid leukemia (AML) remains largely unexplored.
Purpose of the Study:
- To investigate the expression and prognostic significance of ROBO3 in non-M3 acute myeloid leukemia.
- To identify correlations between ROBO3 expression and clinical characteristics, mutations, and patient outcomes.
Main Methods:
- Analysis of transcriptome data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases.
- Statistical analysis of ROBO3 expression in relation to patient age, risk classification, mutations (TP53, RUNX1), overall survival (OS), and event-free survival (EFS).
- Bioinformatics analysis using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) to explore associated pathways.
Main Results:
- ROBO3 was found to be highly expressed in non-M3 AML.
- High ROBO3 expression correlated with increased age, poorer risk classification, and higher frequencies of TP53 and RUNX1 mutations.
- Patients with high ROBO3 expression exhibited significantly worse OS and EFS, even within subgroups receiving intensive chemotherapy.
- Multivariate analysis identified high ROBO3 expression as an independent risk factor for poor OS in specific patient cohorts.
- Pathway analysis indicated that high ROBO3 expression affects cell adhesion and extracellular matrix pathways.
Conclusions:
- ROBO3 is upregulated in non-M3 AML.
- High ROBO3 expression is associated with adverse clinical features and poor survival outcomes.
- ROBO3 may serve as a valuable biomarker for predicting prognosis in non-M3 AML patients.
