A Set of miRNAs, Their Gene and Protein Targets and Stromal Genes Distinguish Early from Late Onset ER Positive Breast Cancer

Autor(es):Mostrar menos -

Bastos, E. P. ^[1] ; Brentani, H. ^[2] ; Pereira, C. A. B. ^[3] ; Polpo, A. ^[4] ; Lima, L. ^[2] ; Puga, R. D. ^[5] ; Pasini, F. S. ^[1] ; Osorio, C. A. B. T. ^[6] ; Roela, R. A. ^[1] ; Achatz, M. I. ^[7] ; Trape, A. P. ^[8] ; Gonzalez-Angulo, A. M. ^[8] ; Brentani, M. M. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Med, Oncol & Radiol Dept, Lab Med Invest LIM 24 24, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Sch Med, Inst & Dept Psychiat, Lab Med Invest LIM 23 23, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Math & Stat Inst, Sao Paulo - Brazil

^[4] Univ Fed Sao Carlos, Dept Stat, Sao Paulo - Brazil

^[5] Einstein Hosp, Sao Paulo - Brazil

^[6] AC Camargo Canc Ctr, Dept Pathol, Sao Paulo - Brazil

^[7] AC Camargo Canc Ctr, Dept Oncogenet, Sao Paulo - Brazil

^[8] Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX 77030 - USA

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 11, n. 5 MAY 6 2016.
• Citações Web of Science: 1

Resumo

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). We proposed that differentially expressed miRNAs could regulate genes and proteins underlying aggressive phenotypes of breast tumors in YA patients when compared to those arising in MA patients. Objective: Using integrated expression analyses of miRs, their mRNA and protein targets and stromal gene expression, we aimed to identify differentially expressed profiles between tumors from YA-BC and MA-BC. Methodology and Results: Samples of ER+ invasive ductal breast carcinomas, divided into two groups: YA-BC (35 years or less) or MA-BC (50-65 years) were evaluated. Screening for BRCA1/2 status according to the BOADICEA program indicated low risk of patients being carriers of these mutations. Aggressive characteristics were more evident in YA-BC versus MA-BC. Performing qPCR, we identified eight 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 aggressive clinicopathological characteristics. The expression profiles by microarray identified 602 predicted target genes associated to proliferation, cell cycle and development biological functions. Performing RPPA, 24 target proteins differed between both groups and 21 were interconnected within a network protein-protein interactions associated with proliferation, development and metabolism pathways over represented in YA-BC. Combination of eight mRNA targets or the combination of eight target proteins defined indicators able to classify individual samples into YA-BC or MA-BC groups. Fibroblast-enriched stroma expression profile analysis resulted in 308 stromal genes differentially expressed between YA-BC and MA-BC. Conclusion: We defined a set of differentially expressed miRNAs, their mRNAs and protein targets and stromal genes that distinguish early onset from late onset ER positive breast cancers which may be involved with tumor aggressiveness of YA-BC. (AU)

• Processo FAPESP: 11/06752-9 - Análise dos perfis de expressão gênica e de microRNAs para identificar marcadores associados á agressividade do carcinoma mamário em mulheres jovens
• Beneficiário: Elen Pereira Bastos
• Modalidade de apoio: Bolsas no Brasil - Doutorado