Fig. 2: Sustained PI3K signaling activation is coupled with glycolytic and mitochondrial metabolism transcriptomic signatures.
From: A metabolic synthetic lethality of phosphoinositide 3-kinase-driven cancer
A Phosflow evaluation of PI3K signaling activity in leukemic blasts (wild-type: n = 16 PDX, PI3K-altered: n = 16 PDX). Box plots show minima, maxima, median, and 25% and 75% percentiles. Unpaired Welch-corrected two-tailed t-test (pAktS473) and two-tailed Mann-Whitney tests (pS6S235/236, p4E-BP1T37/46) were run (ns, p > 0.05; ***, p < 0.001). B Heatmap of expression by transcriptomics and clustering analysis of the 75 metabolic genes differentially expressed in PI3K-altered vs wild-type patients (WT: 122 patients, ALT: 33 patients). Differential expression was defined by an absolute log2 fold change >1 and an adjusted p value < 0.05 from DESeq2 analysis (Wald test-adjusted for multiple comparisons). The metabolic pathways enriched in the gene clusters are listed. C Pathway enrichment analysis in PI3K-altered vs wild-type T-ALL samples using the 75 significantly deregulated metabolic genes in PI3K-altered vs WT samples. An over-representative analysis adjusted for multiple comparisons was run with MetaboAnalyst. A positive odds ratio indicates an enrichment in in PI3K-altered samples. Bubble sizes indicate the number of deregulated genes mapped to each pathway. D Gene set enrichment analyses based on the expression of 2141 metabolic genes in 155 patients stratified by their PI3K signaling status (GSEA-based over-representative analysis adjusted for multiple comparisons).
