Proteomic analysis reveals chromatin remodeling and RNA processing as potential therapeutical targets in Neuroblastoma

Neuroblastoma (NB) is the most common solid tumor in children, characterized by high recurrence rates, drug resistance, and significant mortality. In this study, we analyzed the proteomic profiles of NB tissue samples alongside other pathological categories, including ganglioneuroma (GN) and ganglioneuroblastoma (GNB). Our findings reveal that pathways associated with the cell cycle and DNA replication are significantly upregulated in NB, while oxidative phosphorylation, pyruvate metabolism, and the TCA cycle are notably downregulated compared to GNB and GN. Using weighted gene co-expression network analysis (WGCNA), we identified a core prognostic gene model strongly associated with the unfavorable phenotype of NB, primarily related to RNA processing and chromatin remodeling. Notably, ALYREF and SMARCA4 emerged as potential prognostic biomarkers for NB. Furthermore, by mapping our core prognostic gene models onto drug-perturbed transcriptome profiles from the L1000FWD and CMap databases, we identified five promising repurposing drugs for NB. Among these, Mocetinostat and Clofarabine were validated as effective treatments in two NB cell lines, offering valuable insights for the development of novel targeted therapies in neuroblastoma.