Abstract 1276: Nucleolin has prognostic value in neuroblastoma patients

Abstract

Abstract Background: Neuroblastoma (NB) represents the most frequent form of extracranial solid tumor of infants, responsible for 15% of childhood cancer deaths. Nucleolin (NCL) prognostic value in NB was here investigated. Methods: NCL protein expression was evaluated in NB patients at diagnosis and after induction chemotherapy. NCL mRNA prognostic value was first assessed in a cohort of 20 stage M NB patients and confirmed in the MultiPlatform786 including 786 NB patients of all stages. Overall and event-free survival curves were plotted by Kaplan-Meier method and compared by log-rank test. Findings: NCL protein resulted significantly overexpressed in NB tumors compared to the non tumoral counterpart, and higher in stage M compared to stage L patients. In the stage M cohort and in MultiPlatform786 dataset, patients with high NCL mRNA expression revealed a significant lower survival probability than those with low NCL expression. In MultiPlatform786 dataset, NCL mRNA expression was significantly higher in patients with age >18 months, in stage M and in MYCN amplified tumors than in patients with age ˂18 months and in stage L or MS and with MYCN non amplified tumors, respectively. Multivariate analysis suggested NCL has a significant prognostic value even in the model adjusted for established prognostic markers. NCL significantly stratified patients with age <18 and age >18, stage M, >18 months and stage M tumor, stages L or MS, and with MYCN not amplified. A significant correlation between NCL and MYCN, MYC, and TERT was found in two independent datasets. Gene set enrichment analysis revealed a significant positive enrichment of MYC target genes and genes involved in telomerase maintenance. NCL protein resulted down-modulated after chemotherapy, in association with morphological features of neuroblastic differentiation. Interpretation: NCL is a novel and independent prognostic marker for NB. Funding: IMH-EuroNanoMed II-2015 (ER-2015-2360441-Eranet) and AIRC IG n. 24397 to PF. Citation Format: Davide Cangelosi, Chiara Brignole, Veronica Bensa, Roberto Tamma, Fabiana Malaguti, Barbara Carlini, Enzo Calarco, Patrizia Perri, Domenico Ribatti, Nuno A. Fonseca, Joao N. Moreira, Alessandra Eva, Loredana Amoroso, Massimo Conte, Alberto Garaventa, Angela R. Sementa, Maria V. Corrias, Mirco Ponzoni, Fabio Pastorino. Nucleolin has prognostic value in neuroblastoma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1276.