title: A Set of miRNAs, Their Gene and Protein Targets and Stromal Genes Distinguish Early from Late Onset ER Positive Breast Cancer.
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). 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Oncology and Radiology Department, Laboratory of Medical Investigation 24 (LIM 24), University of Sao Paulo, Medical School, São Paulo, Brazil.
authors.forename: E P
authors.initials: EP
authors.lastname: Bastos
authors.affiliation: Laboratory of Medical Investigation 23 (LIM 23), Institute and Department of Psychiatry, University of Sao Paulo, Medical School, São Paulo, Brazil.
authors.forename: H
authors.initials: H
authors.lastname: Brentani
authors.affiliation: Mathematics and Statistic Institute, University of Sao Paulo, São Paulo, Brazil.
authors.forename: C A B
authors.initials: CA
authors.lastname: Pereira
authors.affiliation: Department of Statistics, Federal University of Sao Carlos, São Paulo, Brazil.
authors.forename: A
authors.initials: A
authors.lastname: Polpo
authors.affiliation: Laboratory of Medical Investigation 23 (LIM 23), Institute and Department of Psychiatry, University of Sao Paulo, Medical School, São Paulo, Brazil.
authors.forename: L
authors.initials: L
authors.lastname: Lima
authors.affiliation: Einstein Hospital, São Paulo, Brazil.
authors.forename: R D
authors.initials: RD
authors.lastname: Puga
authors.affiliation: Oncology and Radiology Department, Laboratory of Medical Investigation 24 (LIM 24), University of Sao Paulo, Medical School, São Paulo, Brazil.
authors.forename: F S
authors.initials: FS
authors.lastname: Pasini
authors.affiliation: Department of Pathology of A.C. Camargo Cancer Center, São Paulo, Brazil.
authors.forename: C A B T
authors.initials: CA
authors.lastname: Osorio
authors.affiliation: Oncology and Radiology Department, Laboratory of Medical Investigation 24 (LIM 24), University of Sao Paulo, Medical School, São Paulo, Brazil.
authors.forename: R A
authors.initials: RA
authors.lastname: Roela
authors.affiliation: Department of Oncogenetics of A.C. Camargo Cancer Center, São Paulo, Brazil.
authors.forename: M I
authors.initials: MI
authors.lastname: Achatz
authors.affiliation: Department of Breast Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, United States of America.
authors.forename: A P
authors.initials: AP
authors.lastname: Trapé
authors.affiliation: Department of Breast Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, United States of America.
authors.forename: A M
authors.initials: AM
authors.lastname: Gonzalez-Angulo
authors.affiliation: Oncology and Radiology Department, Laboratory of Medical Investigation 24 (LIM 24), University of Sao Paulo, Medical School, São Paulo, Brazil.
authors.forename: M M
authors.initials: MM
authors.lastname: Brentani
mesh_terms: D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D011960:Receptors, Estrogen / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; D011960:Receptors, Estrogen