A comparative network analysis of high-risk MYCN amplified and high-risk MYCN non-amplified neuroblastoma patients

Neuroblastoma is the most common extracranial solid tumor in children. Under contemporary staging guidelines, amplification of MYCN, defined as possessing 10 or more copies of the MYCN gene, is sufficient to classify a patient as high-risk. We aim to investigate the complex genetic landscape of neuroblastoma through a network biology perspective, focusing on complex protein-protein interaction (PPI) networks. Reanalyzing three historical neuroblastoma RNA-Seq datasets, we conducted a comparative network analysis of high-risk MYCN amplified patients and high-risk MYCN non-amplified patients to identify PPI networks that serve as predictive biomarkers for developing high-risk disease. We used R scripts to extract the top 100 most highly expressed genes from each dataset and then analyzed the expression profiles using Proteinarium, a network analysis tool that identifies clusters of patients with shared PPI networks. Statistically significant clusters were annotated and analyzed for network similarity between datasets. Our study isolated four significant clusters with majority high-risk MYCN amplified patients. We annotated the genes unique to high-risk MYCN amplified patients and identified several potential network biomarkers for this particular genotype of neuroblastoma, including ribosome biogenesis (RPL7A, RPL30, RPL35, RPS8), heat shock protein (HSPA8, HSP90AA1, HSP90AB1), matrix metallopeptidase (MMP2, MMP9, MMP13), and collagen (COL2A1, COL5A3, COL6A2, COL11A1, COL16A1) gene networks. The results of this study provide potential therapeutic targets for high-risk MYCN amplified neuroblastoma.