(A) 46 up-regulated and 27 down-regulated genes from Figure 5D were queried using the mRNA expression dataset
from TCGA HNSCC project, which includes 279 tumor and 16 mucosa specimens.
Significant up-regulation of 13/46 activated genes (red), and down-regulation of
10/27 repressed genes (blue) are detected in TCGA tumors compared to normal
samples (fold change ≥1.5, student t-Test with FDR < 1%
multivariate comparison correction cut off). (B) Three publicly available
datasets of gene profiling microarrays were investigated, which included a total
of 125 (67 metastatic and 58 non-metastatic) HNSCC tissues. Pearson correlation
coefficients of gene expression between p63 and potential target genes were
calculated, and genes exhibiting statistically significant correlation are
presented. The line indicates p<0.05. (C) RNA was isolated from the skins
of ΔNp63α transgenic mice (red). qRT-PCR was performed to quantify
gene expression levels with a statistically significant increase compared with
their age-matched non-transgenic littermates (blue, p<0.05). The data
were calculated from triplicates of one representative experiment and presented
as the mean ± SD. (D) Human HNSCC and normal mucosa frozen sections were
stained for cREL, ΔNp63, and TAp73, and intensities within nuclei or
cytoplasm in three 200X fields per slide were acquired and quantified using an
Aperio Scanscope and Cell Quantification Software (Vista, CA, USA), and
presented as mean histoscores ± SD for 8-13 samples. * p<0.05,
HNSCC vs normal mucosa by t-tests. (E) Immunohistochemistry comparing
transcription factors JUNB and FOSL1 nuclear staining in human HNSCC tissue
array. Images were acquired using an Aperio Scanscope at 200X magnification, and
staining intensity was quantified using Aperio Cell Quantification Software.
Tumor protein expression of evaluable specimens for JUNB and FOSL1 (n=66) and
mucosa (n=11) samples. Student t-test, p<0.05 (F) Associations in
expression levels between the transcription factors nuclear cREL with targets
nuclear JUNB and IKKε (stage III tumors), nuclear cREL with nuclear FOSL1
(in all tumor stages), and nuclear TP63 with nuclear SERPINE1/PAI1 (metastatic
tumors). A non-directional test for the significance of the Pearson
Product-Moment Correlation Coefficient with the computed histoscores for each
protein was used.