ABSTRACT: Breast cancer (BC) in young adult patients (YA), has a more aggressive biological behavior and is associated with a worse prognosis than BC arising in middle aged patients (MA) partly explained by distinct biological features. Deregulated microRNAs (miRs) may had been implicate in modulating genes associated to YA-BC. Objective: Using miRs, their targets mRNA, proteins and stromal genes expression profiles, our aim was to identify differentially expression profiles between tumors from YA and MA. Methodology and results: Samples of ER+ invasive ductal breast carcinomas, divided into 2 groups: YA-BC (35 years or less, n=25) or MA-BC (50-65 years, n=25) were evaluated. All patients indicated low risk of carrying BRCA1/2 mutation. Aggressive characteristics such as large tumor size and advanced histological grade were more evident in YA-BC tumors versus MA-BC. Performing qPCR, we identified 8 miRs differentially expressed (miR-9, 18b, 33b, 106a, 106b, 210, 518a-3p and miR-372) between YA-BC and MA-BC tumors with high confidence statement, which were associated with worse clinico pathological biomarkers. Combined results from in silico prediction with mRNA expression profiles by microarray, identified 602 genes pointing to enriched biological functions related to proliferation, cell cycle and development. Performing RPPA, 24 targets proteins expression differed between both groups. Combination of eight mRNA targets (ESR1, RPS6KA1, YWHAZ, BCL7, PARP12, DUSP2, DUSP8 and PIGS) or the combination of eight target proteins (RAF1, BCL2L1, EIF4E, STAT5A, PARP1, ESR1, RPS6KA1 and YWHAZ) defined an indicator able to classify individual samples into YA-BC or MA-BC groups. A network was belted to protein-protein interaction including regulatory complexity by miRs reveling important biological processes such as proliferation, development and metabolism in YA-BC. Fibroblast-enriched stroma expression profile resulted in 308 stromal genes differentially expressed between YA-BC and MA-BC related to proliferation, differentiation, maturation and metabolism pathways. Conclusion: The differentially expressed miRNAs, their target genes, proteins and stromal genes distinguished early onset from late onset breast cancer and suggested that biological characteristics in YA-BC may be involved with tumor aggressiveness.
