Circulating Beta3-Adrenoreceptor as Novel Independent Biomarker for Risk Assessment in Neuroblastoma Patients

Neuroblastoma (NB) remains a challenge due to the lack of robust prognostic biomarkers for risk stratification and treatment guidance. The β3-adrenergic receptor (β3-AR) is implicated in tumor progression and metastasis. The present study evaluates the detection of β3-AR in different tissues and its correlation with survival and clinical characteristics of NB patients. β3-AR expression was analyzed in bone marrow (BM), peripheral blood (PB), circulating tumor cells (CTCs), disseminated tumor cells (DTCs), and tumor biopsies by flow cytometric analysis and immunofluorescence. Receiver Operating Characteristic (ROC) curves, Fisher's exact test, and Kaplan-Meier curves were used to investigate the validity of β3-AR as a prognostic marker. Statistical analyses were performed by R software and MedCalc. In our cohort of 45 NB patients, β3-AR expression in PB was significantly higher compared to healthy controls (p = 1.839e-07 at diagnosis; p = 0.0006 at follow-up, p < 0.001) and showed strong correlation across tissues (r > 0.72). High β3-AR expression in DTCs at diagnosis (≥ 96.5%) was associated with shorter event-free survival (p = 0.0005). Elevated β3-AR in BM at diagnosis predicted worse overall survival (p = 0.0076). At follow-up, increased β3-AR expression in PB correlated with shorter overall survival (27 months vs. not reached, p = 0.0015). These findings highlight β3-AR as a promising prognostic biomarker for NB risk stratification and disease progression.