Figure 5
Functional impact of the four peritumor-associated prognostic miRNAs. (a,b) Unsupervised clustering analysis (a) and box plot (b) representing the expression of 690 genes positively (mRNAs-PCm) and negatively (mRNAs-NCm) correlated with the four prognostic miRNAs and differentially expressed between peritumoral tissues and their normal counterparts (P<0.05) in the Italian National Cancer Institute ‘Regina Elena’ head and neck squamous cell carcinoma cohort. (c) Box-plot representing the expression of 457 genes positively (mRNAs-PCm) and negatively (mRNAs-NCm) correlated with the four prognostic miRNAs and differentially expressed between tumor tissues and their normal counterparts (P<0.05) in the TCGA head and neck squamous cell carcinoma cohort. (d) Box plot representing the overall expression of the subset of cell cycle-related genes negatively (N=42) and positively (N=91) correlated with the expression of prognostic miRNAs (P<0.05) from the analysis of the Italian National Cancer Institute ‘Regina Elena’ data set. (e) Box plots showing the differential expression of Ki-67 mRNA among tumor, peritumoral, and normal tissues (ANOVA test, P<0.05). (f) Graph representing the percentages of patients showing <20% or ≥ 20% of Ki-67-positive cells in tumoral, peritumoral, and normal tissues (statistical significance calculated by 3 × 2 chi squared test (P<0.05), ANOVA test P=0.06) (see also Supplementary File 5). (g) Representative immunostaining of Ki-67 protein expression in formalin-fixed paraffin-embedded tissues from head and neck squamous cell carcinoma. The percentage of Ki-67-positive cells is indicated in each panel. N, normal tissue; PT, peritumoral tissue; T, tumor tissue.
