Fig. 1
Predominant alteration of keratinization-TP53 regulation axis in LACC. A Predominantly altered genes in LACC (PAG-LACC). Mutations per megabase in each patient are shown in the top panel. SMG mutations (2nd panel), alterations by HPV genome integration (3rd panel), and CNAs (amplification in red and deletion in blue; 4th panel) detected in each patient for the indicated genes are shown. Alteration frequencies are shown on the right, and the indicated clinical parameters for each patient are shown in the bottom. B-D Comparisons of frequencies of SMG mutations (B), alterations by HPV genome integration (C), and CNAs (D) between our LACC cohort and the two previous early-stage tumor-enriched cohorts. Red labels indicate the genes (PAG-LACC) having significantly (p < 0.05 by proportional test) higher alteration frequencies in our LACC cohort than in the early-stage tumor-enriched cohorts. *, p < 0.05; **, p < 0.01; ***, p < 0.001. n = 251, 289, and 102 patients for our, TCGA, and Huang et al. cohorts, respectively, for SMG mutations; n = 251, 178, and 45 patients for our, TCGA, and Huang et al. cohorts, respectively, for alterations by HPV genome integration and CNAs. E mRNAs, proteins, phosphorylated peptides up-regulated in tumors harboring the alterations (SMG, HPV integration, or CNA) in any of the indicated PAG-LACC. The colored bar represents the gradient of log2-fold-changes of abundances for mRNAs, proteins, or phosphorylated peptides relative to their median levels. F Cellular pathways enriched by mRNAs (Gene) or proteins + phosphoproteins (Prot) correlated with alterations of the indicated PAG-LACC. The heat map shows the enrichment significance (p value from ConsensusPathDB) of each pathway by the mRNAs or proteins + phosphoproteins as –log10(p). G Network model describing interactions among the mRNAs (blue node center), proteins (blue node border), or phosphoproteins (blue circled P) that have significant correlation with alterations of the PAG-LACC (red labeled) and are involved in keratinization and apoptosis/TP53 regulation. Gray nodes indicate molecules added to the pathways to increase connections among the nodes. Solid arrows, direct activations; dotted arrows, indirect activations; gray lines, protein–protein interactions; thick lines, plasma membrane