Fig. 3: Transcriptomic and proteomic analysis of ANA/PAL-Sensitive and ANA/PAL-Resistant cases at C1D15.
A Schematic of samples analyzed by RNA-sequencing and mass spectrometry. B Ki67C1D15 of ANA/PAL-Sensitive (n = 19 samples) or -Resistant tumors (n = 9 samples). Statistics calculated with two-tailed Mann–Whitney U test. C PCA and D volcano plot of differentially expressed genes by DEseq2. −Log10 p-adj values are plotted on the y-axis, and E top oncogenic pathways significantly up or downregulated by Hallmark GSEA analysis in Resistant cases are shown. NES Normalized enrichment score. F Pearson correlation of Ki67C1D15 and mRNA expression of genes of interest in Resistant (y-axis) versus Sensitive (x-axis) tumors. G Box plots of relevant protein effectors involved in cell cycle, PI3K/AKT/mTOR, and interferon pathways in Sensitive (n = 12 samples) or Resistant (n = 5 samples). Statistics calculated with two-tailed Mann–Whitney U test. As also in (B), boxplots show the median (center line), the 25th and 75th percentiles (lower and upper box bounds), and whiskers extending to the most extreme data points within 1.5× the interquartile range. H Hallmark pathway analysis of protein expression in Sensitive and Resistant tumors. I Hallmark pathway alterations shared at RNA and protein levels in Resistant versus Sensitive tumors. J Spearman correlation between RNA and protein expression in 14 paired samples. Candidate genes/proteins belonging to assigned Hallmark pathways were plotted. K Summary schematic of enriched oncogenic pathways at RNA and/or protein level in Resistant tumors at C1D15 with identified targetable effectors of interest and relevant inhibitors.
