Fig. 4: Association of gene expression with sensitivity toward MI-773.

a Venn diagram showing the number of Affymetrix Human Genome U133 plus 2.0 probe sets significantly associated with MI-773 Abs IC₅₀ according to the t-test, Limma and Spearman statistical tests (adjusted p-value < 0.05). b Volcano plot showing levels of significance of individual genes for the association of their expression levels with MI-773 Abs IC₅₀ values. x-axis, log₂ fold difference of gene expression level between MI-773 response groups; y-axis, Limma adjusted p-values on log₁₀ scale. The red and blue dots show the genes having an expression significantly associated with the response to MI-773 (significant adjusted p-value in Limma, t-test and Spearman) and a log₂ fold difference >0.5 (red dots) or <−0.5 (blue dots) as calculated by Limma. The grey dots depict the genes neither significantly associated with the response to MI-773 (adjusted p-value ≥ 0.05 in Limma, t-test and Spearman) nor having fold difference below 0.5 of amplitude. c Heatmap with unsupervised hierarchical clustering of 237 differentially expressed genes (fold difference > ±0.5). First upper bar shows response groups to MI-773, second upper bar shows the type of cancer cell lines (haematologic or solid). d KEGG enrichment analysis of the 113 genes whose high expression was positively associated with MI-773 sensitivity. e Spearman correlation analysis between MI-773 Abs IC₅₀ values and the gene expression-based predictive score. Upper plot: all CLs, lower plot: wild type TP53 CLs only. The solid line shows the correlation between the MI-773 Abs IC₅₀ values and the gene expression-based predictive score. Dots are coloured according to their response groups to MI-773. f Decisional tree performance for the CL classification into groups of sensitive and resistant to MDM2 inhibition. RR: response rates. Left: MI-773, right: Nutlin-3a.