Fig. 3

Transcriptomic, epigenomic and protein characterization of LUSC transformation. a Heatmap showing the expression of genes predictive of LUSC subtype in the LUSC and T-LUSC samples in our cohort (left) and bar plot indicating the percentage of each subtype present in our LUSC and T-LUSC cohorts, with comparison to Wilkerson et al.18. p-value was calculated using the Chi-Square test assessing the distribution differences between cohorts. PLSDA analyses on the transcriptome (b) and (c) methylome of T-LUAD and T-LUAD samples, and of control LUAD and SCLC samples. Circles delimiting each sample group were calculated with 90% interval of confidence. d Pathway enrichment analyses on DEGs of the T-LUSC versus T-LUAD comparison. e Bar plot showing differential expression of phosphorylated proteins involved in the AKT, Wnt and DNA damage response pathways, as determined by an antibody array on microdissected LUAD and LUSC tissue from adenosquamous clinical samples (see Additional file 1; Table S4). f Western blot showing expression/phosphorylation of proteins of interest on the same samples analyzed by protein array. g MYC protein expression levels (IHC score) on matched T-LUAD and T-LUSC components in adenosquamous samples. h Plot exhibiting differentially methylated transcription factor binding domains in T-LUSC versus T-LUAD. Sample IDs in black and red indicate that they come from a combined histology specimen or a pre-/post-transformation specimen, respectively. p-values legend: *p < 0.05, **p < 0.01