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

Based on cytogenetic and genetic markers for risk stratification, patients with acute myeloid leukemia (AML) show a very heterogeneous prognosis. Overexpression of ROBO3 has been reported to confer an unfavorable outcome in AML. However, it is unclear whether the prognostic effect of ROBO3 on AML is interfered by treatment option. In this study, we analyzed 148 AML patients with ROBO3 expression information using the Cancer Genome Atlas (TCGA) database. We found ROBO3 was a new prognostic marker in AML administered chemotherapy. In multivariable analyses, high ROBO3 expression independently predicted lower EFS (HR = 1.820, P  = 0.035) and OS (HR = 2.073, P = 0.011) when adjusting for other well-known prognostic factors. We further found allogeneic hematopoietic stem cell transplantation(allo-HSCT) could overcome the inferior outcomes associated with high ROBO3 expression. Construction nomograms including ROBO3 and other clinical parameters for predicting OS and EFS exhibited satisfactory accuracy and discrimination. Functional enrichment identified ROBO3 was involved in immune-related pathways. ssGSEA demonstrated notable differences and correlation in the immune cell infiltration. Notably, we confirmed that ROBO3 suppression could inhibit leukemia cell growth in vitro. Overall, our results provide new insights into the role of ROBO3 in AML, with promising clinical implications.