Fig. 3
PI3K-AKT-mTOR pathway changes following PIKTOR treatment. (A) Pathway changes following PIKTOR treatment. Canonical pathway enrichment from differential gene expression results between pre- and post-PIKTOR biopsies. DESeq2 results from independent Responder and Non-responder analyses were input into Ingenuity Pathway Analysis, and results from the canonical pathway output is grouped by broader common pathways. Z-score is represented by color, and –log(p-value) is displayed by bar chart height, with values for responders extending to the left of the origin, and values for non-responders to the right. (B) Unsupervised hierarchical clustering levels of PI3K/AKT/mTOR (PAM) pathway proteins in microdissected tumors that metastasized to lymph node reveals heterogeneous signaling profiles. Pre and post samples are represented by white and black triangles, respectively. (C) Biological signaling pathway superimposed with log2 fold changes in average protein levels post-PIKTOR compared to pre-PIKTOR. Lymph node metastasis specimens only (n = 6). (D) Statistically significant proteins in cell stress, protein translation, T cell receptor activation, and cell cycle pathways were elevated in the post-PIKTOR treated patient specimens compared to pre-PIKTOR. Violin plots: solid line is group median, with quartiles (dashed lines)