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Fig. 2 | Cancer Cell International

Fig. 2

From: Proteo-transcriptomics meta-analysis identifies SUMO2 as a promising target in glioblastoma multiforme therapeutics

Fig. 2

(available at Cancer Cell Line Encyclopaedia, CCLE platform) showed that classically and often used glioblastoma cell lines had a significant expression of SUMO2 isoforms vs other isoforms. G RNA Seq data analysis from TCGA platform revealed that glioblastoma tissue sub-types (classical, mesenchymal, neural, proneural; based on the molecularly distinct transcriptome, hence plasticity) have significant expression of SUMO2 in all sub-type categories. Note that GBM molecular subtype signature information is used in clinical practice to determine GBM therapy's nature. H Microarray analysis on glioblastoma sub-types derived tumours cells (classical, mesenchymal, neural, proneural), from data available on HGCC platform confirms significant expression of SUMO2 in all GBM subtypes. 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. 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

SUMO2 isoform is highly expressed across glioblastoma heterogeneity: A RNA Seq data (GEO-GSE59612) analysis from glioblastoma patients' tumour samples revealed that the whole glioblastoma tumour, that is, both core and margin (including residual tumour cells left behind after surgical resection) expresses significant levels of SUMO2 isoforms vs normal controls and other SUMO isoforms. B Glioblastoma cancer stem cells (CSCs) RNA Seq data analysis from the Allen Brain Atlas repository (IVY-GAP) reveals that CSCs are significantly enriched in SUMO2 isoforms vs other isoforms. C RNA Seq data analysis of human glioblastomas that were in contact with neural stem cell zones of the ventricular sub-ventricular regions (VSVZ +) in the brain as well as glioblastomas that were not in VSVZ contact (VSVZ-, non-contact) showed high SUMO2/3 expression vs other isoforms. VSVZ refers to the Ventricular Subventricular zone neural stem cell niche. Plus sign refers to glioblastomas in contact with ventricular-subventricular neural stem cell regions. VSVZ contact by GBMs has been noted for negatively impacting patient survival. Minus sign refers to glioblastoma bulk populations that did not contact ventricular neural stem cell lining, hence are in a different microenvironment. D Microarray data (GEO-GSE7696) analysis from human primary and recurrent glioblastoma tumour samples, where patients were subjected to either radiotherapy or chemo-radiotherapy (Temozolomide-chemo), showed that surviving tumour cells were enriched in SUMO2 isoform; hence SUMO2 must be directly or indirectly involved in enabling GBM cells survival and resistance against Temozolomide chemo-radio therapeutic regimes. Probe 1 and Probe 2 refers to distinct cDNA probes used in microarray studies. E Kaplan Meier Survival plot from astrocytoma/GBM dataset (GSE-4271-GPL96) showed a significant association of high SUMO2 expression with reduced patient survival vs highly homologous isoform SUMO3. p value was derived from the log-rank test. High expression is indicated in red and low expression is indicated by blue-coloured curves. The numbers of patients in each group are indicated in the figure panel. F Top sub-panel: Microarray data (GEO-GSE72217) analysis of glioblastoma patients' tumour-derived cells from Human Glioma Cell Culture Repository, HGCC, showed significantly high expression of SUMO2 isoform vs other SUMO isoforms, Middle sub panel: RNA Seq data analysis (SRA-PRJNA508446) of glioblastoma tumour cells that were freshly isolated from glioblastoma patients' tumour tissues (primary cells), also showed significant expression of SUMO2 isoform, Bottom sub-panel: RNA Seq data

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