Fig. 5

BGA002-RA treatment leads to mTOR complex inhibition in MNA-NB. A mRNA expression of genes involved in the mTOR pathway in an neuroblastoma dataset (E-MTAB-1781). The violin plot represents normalized (z-score) mRNA expression for non-MNA and MNA patients. Each dot represents an individual sample; the middle line indicates the median. Statistic: Wilcoxon matched-paired test. ****p ≤ 0.0001. B Kaplan–Meier plots for the probability of overall survival over time for neuroblastoma patients (E-MTAB-1781). The dark gray line indicates patients with normalized gene expressions higher than 1 (z-score > 1). The p-value is indicated in the middle (Log-rank test). C-D The gene names listed in the middle are referring to both panels. (MNA cell-lines: KELLY, CHP-134, IMR-32, SMS-KAN, LS, MHH-NB-11, NGP, SIMa, GI-LI-N; MNA-p53mut: SK-N-B [2] c, NMB, LAN-1; single copy: NBL-S, LAN-6, SH-SY5Y; single copy and p53mut: SK-N-F1). C a heatmap representing Pearson correlation coefficients for mTOR pathway genes. D Heatmap of the gene expression variation after 12 hours of treatment in neuroblastoma cell lines. Columns represent cell lines (grouped according MYCN amplification and p53 mutation status), rows represent genes belonging to the mTOR pathway, and the color scale represents the log₂ fold change over the control (untreated). The gray color indicates unexpressed genes. E mTOR pathway activity measured through Western blot in the Kelly cell line (MYCN amplified, p53 wild type) after 24 hours of treatment (representative image is 1 out 2 biological replicates). F mTOR pathway activity quantification normalized over the control (n = 2 experiments, ** p-value ≤0.0001, ANOVA). CTRL, control. Where indicated in the figure: *, p < 0.05; **, p < 0.01; ***, p < 0.001; ****, p < 0.0001