Figure 6. Overview of the dynamic expression changes observed in the 4-NQO model projected in pathways pertinent to human oral preneoplasia (OPL) and squamous cell carcinoma (OSCC).

This figure shows the coherence between main molecular events occurring in the 4-NQO mouse model (EGS, IGS, LGS, PGS) and those involved in human oral preneoplasia and OSCC. Mitogen-activated protein kinase (MAPK), apoptosis, cell cycle, and the nuclear factor NF-κB (NFKB) pathways are dysregulated during oral tumorigenesis and were found to be correlated (p<0.01) with one or more of mouse gene subsets as indicated by blue (PGS), green (EGS), red (LGS) and turquoise (IGS) arrows respectively (A). Those correlations were consistent with drug sensitivity patterns in established squamous cell carcinoma cell lines; corresponding targets are highlighted (yellow) within the pathways A, B. Patients whom OPL were enriched for the mouse EGS were at increased risk of developing OSCC (borderline statistical significance) C. OSCC enriched for the mouse TGS harbor genomic features (amplification region 11q13) that may be associated with increased sensitivity to MEK1/2 inhibitors D. Abbreviations: TCGA: The Cancer Genome Atlas; GDSC: Genomics of Drug Sensitivity in Cancer; EGS: Early Gene Subset; IGS: Intermediate Gene Subset; LGS: Late Gene Subset; PGS: Progressive Gene Subset.