title: A serum microRNA signature predicts tumor relapse and survival in triple-negative breast cancer patients.
abstract: OBJECTIVE
  Triple-negative breast cancers (TNBC) are associated with high risk of early tumor recurrence and poor outcome. Common prognostic biomarkers give very restricted predictive information of tumor recurrences in TNBC. Human serum contains stably expressed microRNAs (miRNAs), which have been discovered to predict prognosis in patients with cancer. The purpose of this study was to identify circulating biomarkers able to predict clinical outcome in TNBC.
  
  
  METHODS
  We performed genome-wide serum miRNA expression and real-time PCR analyses to investigate the ability of miRNAs in predicting tumor relapse in serum samples from 60 primary TNBC. Patients were divided into training and testing cohorts.
  
  
  RESULTS
  By Cox regression analysis, we identified a four-miRNA signature (miR-18b, miR-103, miR-107, and miR-652) that predicted tumor relapse and overall survival. This miRNA signature was further validated in an independent cohort of 70 TNBC. A high-risk signature score was developed and significantly associated with tumor recurrence and reduced survival. Multivariate Cox regression models indicated that the risk score based on the four-miRNA signature was an independent prognostic classifier of patients with TNBC.
  
  
  CONCLUSIONS
  This signature may serve as a minimally invasive predictor of tumor relapse and overall survival for patients with TNBC. This prediction model may ultimately lead to better treatment options for patients with TNBC.
authors.affiliation: Department of Genetics, Institute for Cancer Research, Oslo University Hospital-Radiumhospitalet, Oslo, Norway. Department of Research, Vestre Viken, Drammen, Norway.
authors.forename: Kristine
authors.initials: K
authors.lastname: Kleivi Sahlberg
authors.affiliation: Oncology Experimental Therapeutics Unit, IRCCS Clinical and Research Institute Humanitas, Rozzano-Milan, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Bottai
authors.affiliation: Department of Oncology, Division of Surgery and Cancer Medicine, Oslo University Hospital-Radiumhospitalet, Oslo, Norway. K.G. Jebsen Centre for Breast Cancer, Institute for Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Bjørn
authors.initials: B
authors.lastname: Naume
authors.affiliation: Division of Molecular Biology of Breast Cancer, University Women's Clinic, Heidelberg, Germany. Molecular Epidemiology, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Burwinkel
authors.affiliation: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: George A
authors.initials: GA
authors.lastname: Calin
authors.affiliation: Department of Genetics, Institute for Cancer Research, Oslo University Hospital-Radiumhospitalet, Oslo, Norway. K.G. Jebsen Centre for Breast Cancer, Institute for Clinical Medicine, University of Oslo, Oslo, Norway. libero.santarpia@humanitasresearch.it a.l.borresen-dale@medisin.uio.no.
authors.forename: Anne-Lise
authors.initials: AL
authors.lastname: Børresen-Dale
authors.affiliation: Oncology Experimental Therapeutics Unit, IRCCS Clinical and Research Institute Humanitas, Rozzano-Milan, Italy. libero.santarpia@humanitasresearch.it a.l.borresen-dale@medisin.uio.no.
authors.forename: Libero
authors.initials: L
authors.lastname: Santarpia
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics; D016000:Cluster Analysis; D015331:Cohort Studies; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics*; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011379:Prognosis; D012372:ROC Curve; D059467:Transcriptome; D064726:Triple Negative Breast Neoplasms / Q000097:blood* / Q000235:genetics* / Q000401:mortality / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs