Fig. 1

Glioblastoma upregulated kinases and coding genes are targets of SUMO2/3 isoforms. A Heatmap of RNA-Seq transcriptome analysis shows comparable upregulation of kinases in primary and recurrent glioblastoma tissue from 168 patients vs normal adjacent control tissues. The colour bar corresponds to per-gene log2 fold change values in compared groups. B Enrichment score plot/Gene set enrichment analysis (GSEA) identifies that upregulated kinases are predominantly involved in promoting the cell cycle. FDR = False Discovery Rate; FDR q value ≤ 0.25, NES = Normalized Enrichment score. Gene sets are ranked according to their normalized enrichment score (NES). NOM p value ≤ 0.05 was considered to be significant in sorting enriched terms. C CytoHubba network analysis of upregulated kinases in primary and recurrent GBMs unveils 25 common hub kinases amongst the top 30 hubs identified in individual networks. Mass spectrometry data from Hendriks et al. (2017 and 2018) identified 19 and 16 hub kinases as targets of SUMO2/3 (marked as an orange square) and SUMO2 (marked as a magenta polygon), respectively. Combined literature search (blue oval) and mass spectrometry data on SUMO2/3 targets amongst the top 25 common hub kinases in primary and recurrent GBMs identified 22 kinases to be targets of SUMO2/3. D A comparison of SUMO isoforms expression in normal whole brain and cerebral cortex alone [RNA Seq dataset from normal tissue (GTEx) gene expression dataset] with primary and recurrent GBM (RNA Seq dataset from TCGA) unveils significant expression of SUMO 1,2 and 3 isoforms. All datasets are reported as mean ± SD. *p < 0.05, **p < 0.01, ***p < 0.001 and ****p < 0.0001; Mean is derived from a statistically significant number of samples, and Student t-test function was used to drive significance. E, F Analysis of Hendriks et al., 2017 mass spectrometry-based proteomics data revealed that a substantial percentage of GBM upregulated kinases and coding genes are targets of SUMO2 isoform (represented as an orange colour fraction in the pie chart). G GSEA analysis of upregulated genes in primary and recurrent GBMs that are identified as targets of SUMO2/3 (via Hendriks LC–MS/MS data) showed enrichment in all hallmarks of cancers-proliferation, metastasis, invasion, EMT, hypoxia, drug resistance, pro-tumourigenic immune cell activation etc. For in-depth details on individual data points and dataset sample size in each graph, please refer to corresponding Additional tables mentioned in the main manuscript text