Integrated systems biology approach using gene network analysis to identify the important pathways and new potential drug targets for Neuroblastoma

Abstract

The complex and heterogeneous nature of neuroblastoma poses a great challenge to the scientific community for developing an effective therapeutic drug. Neuroblastoma tumors show relapse and resistance to available drugs and it is proving to be an obstacle for efficient treatment options. The tumor accounts for about 7% of the malignancies worldwide and is seen mostly in children around one year. Our present study aims to understand various mechanisms underlying Neuroblastoma. The gene interaction network of 92 Neuroblastoma related genes along with a total of 339 functional interactions are used for the gene interaction network construction and analysis. The clustering analysis resulted in four densely interconnected gene clusters. We further performed functional enrichment analysis and found important pathways associated with neuroblastoma in PI3K/AKT pathway, MAPK pathway, Ras pathway, Rap1 pathway, Cytokine- cytokine interaction, Neurotrophin signaling, EGFR tyrosine kinase inhibitor resistance, and VEGF signaling pathways. The predominant genes involved in the enriched pathways are ANGPT2, FGF2, NGFR, NTRK1, NTRK2, PDGFC, TGFA, TP53, VEGFB, VEGFC, BDNF, NRAS, and VEGFA. The topological parameter analysis has shown the genes with more direct interactions are considered as the hub genes and are important in the network. The genes TP53, VEGFA, BDNF, MYCN, and FGF2 with the maximum number of functional interactors, can be used as potential therapeutic targets for Neuroblastoma. The results obtained in our study will be helpful for researchers in better understanding the molecular level associations during the Neuroblastoma progression.