title: MicroRNA profile in very young women with breast cancer.
abstract: BACKGROUND
  Breast cancer is rarely diagnosed in very young women (35 years old or younger), and it often presents with distinct clinical-pathological features related to a more aggressive phenotype and worse prognosis when diagnosed at this early age. A pending question is whether breast cancer in very young women arises from the deregulation of different underlying mechanisms, something that will make this disease an entity differentiated from breast cancer diagnosed in older patients.
  
  
  METHODS
  We performed a comprehensive study of miRNA expression using miRNA Affymetrix2.0 array on paraffin-embedded tumour tissue of 42 breast cancer patients 35 years old or younger, 17 patients between 45 and 65 years old and 29 older than 65 years. Data were statistically analyzed by t-test and a hierarchical clustering via average linkage method was conducted. Results were validated by qRT-PCR. Putative targeted pathways were obtained using DIANA miRPath online software.
  
  
  RESULTS
  The results show a differential and unique miRNA expression profile of 121 miRNAs (p-value <0.05), 96 of those with a FDR-value <0.05. Hierarchical clustering grouped the samples according to their age, but not by subtype nor by tumour characteristics. We were able to validate by qRT-PCR differences in the expression of 6 miRNAs: miR-1228*, miR-3196, miR-1275, miR-92b, miR-139 and miR-1207. Moreover, all of the miRNAs maintained the expression trend. The validated miRNAs pointed out pathways related to cell motility, invasion and proliferation.
  
  
  CONCLUSIONS
  The study suggests that breast cancer in very young women appears as a distinct molecular signature. To our knowledge, this is the first time that a validated microRNA profile, distinctive to breast cancer in very young women, has been presented. The miRNA signature may be relevant to open an important field of research in order to elucidate the underlying mechanism in this particular disease, which in a more clinical setting, could potentially help to identify therapeutic targets in this particular set of patients.
authors.forename: Maria
authors.initials: M
authors.lastname: Peña-Chilet
authors.forename: Maria T
authors.initials: MT
authors.lastname: Martínez
authors.forename: Jose A
authors.initials: JA
authors.lastname: Pérez-Fidalgo
authors.forename: Lorena
authors.initials: L
authors.lastname: Peiró-Chova
authors.forename: Sara S
authors.initials: SS
authors.lastname: Oltra
authors.forename: Eduardo
authors.initials: E
authors.lastname: Tormo
authors.forename: Elisa
authors.initials: E
authors.lastname: Alonso-Yuste
authors.forename: Beatriz
authors.initials: B
authors.lastname: Martinez-Delgado
authors.forename: Pilar
authors.initials: P
authors.lastname: Eroles
authors.forename: Joan
authors.initials: J
authors.lastname: Climent
authors.forename: Octavio
authors.initials: O
authors.lastname: Burgués
authors.forename: Jaime
authors.initials: J
authors.lastname: Ferrer-Lozano
authors.forename: Ana
authors.initials: A
authors.lastname: Bosch
authors.forename: Ana
authors.initials: A
authors.lastname: Lluch
authors.affiliation: Medical Oncology and Hematology Unit, INCLIVA Biomedical Research Institute, Av, Blasco Ibañez, 17, Valencia 46010, Spain. gribasdespuig@gmail.com.
authors.forename: Gloria
authors.initials: G
authors.lastname: Ribas
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D055815:Young Adult
chemical_list: D035683:MicroRNAs