Abstract 5205: Beyond boundaries: ADRB3, a novel prognostic marker in pediatric neuroblastoma

Abstract

Abstract Introduction: Neuroblastoma (NB) is a pediatric tumor arising from immature nerve cells originating from neural crest cells. This malignancy is characterized by a remarkably early onset, with only 10% of cases occurring beyond 5 years of age. According to the INRG classification, ~50% of patients are classified as low risk (L1/L2). Despite advances in treatment, around 20% of these experienced a relapse within 5 years with a mere 10% survival rate. Methods: We investigated the role of the adrenoceptor beta-3 (ADRB3) as a prognostic factor for NB. The samples provided by IRCCS Meyer Children’s Hospital allowed us to measure cytofluorimetric level expression of ADRB3 in tissue biopsies from 43 NBs, in the circulating tumor cells (CTCs) and in the bone marrow cells (BMCs) at onset and at the end of treatment. Further, to study the role of ADRB3 in NB, we used CRISPR-Cas9 to knock down ADRB3 expression in mice model. Results: Results indicate that ADRB3 levels in biopsy at the onset are significantly higher (Wilcoxon test, p = 0.026) in patients with negative outcome than those who achieved complete remission. The R package survival was used to perform Survival curve analysis to further assess the impact of ADRB3 at the onset in biopsy tissues. Results confirmed a significant separation (p = 0.031) between survival curves of patients with high levels and those with low levels, reinforcing its importance as a prognostic factor. Moreover, the same results were found in survival curves (p = 0.038) in low-risk patients, corroborating the importance of ADRB3 levels to discriminate between unfavorable or favorable prognosis. Moreover, post-chemotherapeutic treatment analysis, in both residual CTCs and BMCs, indicated statistically differences in ADRB3 levels between fully recovered patients and deceased. Survival curves, stratified by ADRB3 levels in CTCs post-chemotherapy, a favorable prognosis for patients with low levels (p = 0.0001). Finally, the expression analysis showed that ADRB3 levels in NB cells led to increment of processes associated with the cellular migration and metastasization and in metabolism. Conclusion: Our findings suggest that ADRB3 is a significant prognostic factor for NB. Patients with high ADRB3 expression in biopsy at the onset and after the treatment have a higher risk of unfavorable outcome, even for low-risk patients. In conclusion, our results challenge current classification and prognostic paradigms, highlighting ADRB3's crucial role in NB, contributing to refine risk stratification and unveil a new potential target for liquid biopsy of detecting, analyzing and monitoring CTCs. Citation Format: Gianluca Mattei, Cristina Banella, Francesco Carrozzo, Amada Pasha, Annalisa Tondo, Claudio Favre, Maura Calvani. Beyond boundaries: ADRB3, a novel prognostic marker in pediatric neuroblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5205.