title: Evaluation of microRNA-10b prognostic significance in a prospective cohort of breast cancer patients.
abstract: BACKGROUND
  MicroRNA-10b (miR-10b) has a prominent role in regulating tumor invasion and metastasis by targeting the HOXD10 transcriptional repressor and has been found up-regulated in several tumor types.
  
  
  METHODS
  We evaluated the expression of miR-10b in paired tumor and normal specimens obtained from a prospective cohort of breast cancer patients with at least 36 months follow-up enrolled according to the REMARK guidelines (n = 150). RNA quality was measured and only samples with RNA Integrity Number (RIN) ≥7.0 were analyzed.
  
  
  RESULTS
  The relative expression of miR-10b in tumor as compared to its normal counterpart (RER) was determined by RT-qPCR. miR-10b RERs were higher in the subgroup of patients with synchronous metastases (n = 11, Median 0.25; IQR 0.11-1.02) as compared with patients without metastases (n = 90, Median 0.09; IQR 0.04-0.29) (p = 0.028). In the subgroup of patients without synchronous metastases (n = 90), higher miR-10b RERs were associated with increased risk of disease progression and death in both univariable (HR 1.16, p = 0.021 and HR 1.20, p = 0.015 respectively for 0.10 unitary increase of miR-10b RERs levels) and multivariable (HR1.30, p < 0.001, and HR 1.31, p = 0.003 respectively for 0.10 unitary increase of miR-10b RERs levels) Cox regression models. The addition of miR-10b RERs to the Nottingham Prognostic Index (NPI) provided an improvement in discrimination power and risk reclassification abilities for the clinical outcomes at 36 months. Survival C-indices significantly increased from 0.849 to 0.889 (p = 0.009) for OS and from 0.735 to 0.767 (p = 0.050) for DFS.
  
  
  CONCLUSIONS
  Our results provide evidences that the addition of miR-10b RERs to the prognostic factors used in clinical routine could improve the prediction abilities for both overall mortality and disease progression in breast cancer patients.
authors.affiliation: Laboratory of Oncology, IRCCS Casa Sollievo della Sofferenza, Viale Padre Pio, 71013 San Giovanni Rotondo, (FG), Italy. pparrella@operapadrepio.it.
authors.forename: Paola
authors.initials: P
authors.lastname: Parrella
authors.forename: Raffaela
authors.initials: R
authors.lastname: Barbano
authors.forename: Barbara
authors.initials: B
authors.lastname: Pasculli
authors.forename: Andrea
authors.initials: A
authors.lastname: Fontana
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Copetti
authors.forename: Vanna Maria
authors.initials: VM
authors.lastname: Valori
authors.forename: Maria Luana
authors.initials: ML
authors.lastname: Poeta
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Perrone
authors.forename: Daniela
authors.initials: D
authors.lastname: Righi
authors.forename: Marina
authors.initials: M
authors.lastname: Castelvetere
authors.forename: Michelina
authors.initials: M
authors.lastname: Coco
authors.forename: Teresa
authors.initials: T
authors.lastname: Balsamo
authors.forename: Maria
authors.initials: M
authors.lastname: Morritti
authors.forename: Fabio
authors.initials: F
authors.lastname: Pellegrini
authors.forename: Andrea
authors.initials: A
authors.lastname: Onetti-Muda
authors.forename: Evaristo
authors.initials: E
authors.lastname: Maiello
authors.forename: Roberto
authors.initials: R
authors.lastname: Murgo
authors.forename: Vito Michele
authors.initials: VM
authors.lastname: Fazio
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008207:Lymphatic Metastasis; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D015398:Signal Transduction; D016019:Survival Analysis; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D018398:Homeodomain Proteins; C547183:MIRN10 microRNA, human; D035683:MicroRNAs; D014157:Transcription Factors; C072064:HOXD10 protein, human