Fig. 2

Functional enrichment and network analysis link the HR-NB prognostic signatures with the MCY and PRC2 components of an ESC-like gene signature. a Among the three multigene signatures, we evaluated the over-representation of all six types of functional gene-sets downloaded from MSigDB v3.1. The enriched gene-sets (FDR < 0.01, GS size < 2000) show significant concurrence of MA_hi genes and MN_hi genes (p < 2e-16, odds ratio > 8, the pink and blue circles), regardless of their non-overlap on the gene-level. Additionally, these gene-sets significantly co-occur with the gene-sets what were enriched among genes harboring verified variants at exon (p < 2e-16, odd ratios > 100, the saffron circle and the union of the other two circles). b Rank the 4460 HR-NB associated proteins according to their topological betweenness in the PPI network. c A model of imbalanced ESC-like signatures with PRC2-targets and MYC/MAX-targets at the transcript and protein-protein-interaction (PPI) levels. Weinberg’s group reported that this human ESC-like signature was associated with histologically poorly differentiated tumors (breast, glioma, and bladder cancers). PPI (STRING v9.05) reveals a critical role of MYCN, TP53 and NCAM1 in tuning the prognostic imbalance. Distinct colors code genes for genomic variants, showing transcriptional MYCN-association, or both. We highlight the genes of the identified prognostic GSPs with a larger node-size in the network. d MYC proteins preferentially target MA_hi genes. Network-node colors decode genes with genomic exonic variants, genes showing transcriptional MYCN-association, or both. TF: transcript factor