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Gene Set Enrichment Analysis. Gene Set Enrichment Analysis (GSEA) [28] wasperformed for all selected modulators which sharing common biological function,chromosomal location, or regulation (modules).Functional Analysis. Ingenuity Pathways Analysis (IPA) 8.0 (Ingenuity ® Systems,http://www.ingenuity.com) was used in the set of modulators. Networks were generated basedon Ingenuity Pathways Knowledge Database. Fischer’s exact test was applied to identify thesignificant functions, networks and pathways represented within the respective gene sets. Asresult, it is displayed a score –log(P-value) representing the probability of finding genes innetworks and pathways relative to other genes, assembled them into specificnetwork/pathways based on random chance.RESULTSDNA copy number alterations analysis. According JISTIC analysis, the overall patternof CNAs displayed heterogeneity among all cases showing 142 chromosomal regionsinvolved in gains (1032 genes) and 18 in losses (160 genes) totalizing 1192 genes identified.The most frequent genomic imbalances were gains on chromosomes 16 and 19, and losses onchromosomes 4 and 16 (Table S2).Gene expression analysis. Unsupervised hierarchical clustering analysis was unable toidentify subgroups of tumors, according to the gene expression profile and clinical features(data not shown). Gene expression analysis revealed 3325 significant genes; 1138 were upregulatedand 2187 down-regulated. About 40% (39.7%) of up-regulated and 38% of downregulatedgenes were associated with cellular processes. Significant genes were preferentiallyassociated with cell cycle (http://www.funnet.info/) (Figure S1).Integrative analysis. The integrative analysis by CONEXIC using 1192 up-regulatedgenes and 3325 down-regulated genes with significant G scores, ranked 75 modulators7