title: Circulating cell-free miRNAs as biomarker for triple-negative breast cancer.
abstract: BACKGROUND
  Triple-negative breast cancer (TNBC) accounts for 15-20% of all breast cancer in women globally. This subtype often has early and high recurrence rates resulting in poor survival, partially due to lack of targeted therapies. Therefore, there is an urgent need to identify TNBC-specific biomarkers for early diagnosis and treatment monitoring, and to develop more effective targeted therapy.
  
  
  METHODS
  By using miRCURY LNA array platform, we compared the differential miRNA expressions in plasma of patient with TNBC (n=5) and non-TNBC (n=5), as well as healthy controls (n=5). Potential miRNAs were then validated in a large cohort of patients by real-time PCR.
  
  
  RESULTS
  Ten putative miRNAs from the microarray data that differentially expressed between non-TNBC and healthy controls were identified. In the screening phase (n=90), we selected five miRNAs (miR-92a-3p, miR-342-3p, miR-16, miR-21 and miR-199a-5p) that could discriminate TNBC from non-TNBC for further validation. Results showed that miR-16, miR-21 and miR-199a-5p were underexpressed in TNBC when compared with non-TNBC, and were further validated in a large cohort (n=252). In addition, post-operative plasma levels of miR-16, miR-21 and miR-199a-5p were significantly restored when compared with pre-operative plasma of TNBC. Plasma miR-199a-5p expression in TNBC had significant difference when compared with non-TNBC and healthy controls, the receiver-operator characteristics curve analysis revealed the highest area under curve (AUC=0.8838) among all. The expression levels were associated with TNM stage and tumour subtypes.
  
  
  CONCLUSIONS
  Our data suggest that miR-199a-5p could be a TNBC-specific marker with diagnostic value and provide insights into targeted therapy in the treatment of TNBC.
authors.affiliation: Department of Surgery, the University of Hong Kong, Hong Kong SAR, China.
authors.forename: V Y
authors.initials: VY
authors.lastname: Shin
authors.affiliation: Department of Surgery, the University of Hong Kong, Hong Kong SAR, China.
authors.forename: J M
authors.initials: JM
authors.lastname: Siu
authors.affiliation: Department of Surgery, the University of Hong Kong, Hong Kong SAR, China.
authors.forename: I
authors.initials: I
authors.lastname: Cheuk
authors.affiliation: Department of Surgery, the University of Hong Kong, Hong Kong SAR, China.
authors.forename: E K O
authors.initials: EK
authors.lastname: Ng
authors.affiliation: 1] Department of Surgery, the University of Hong Kong, Hong Kong SAR, China [2] The Hong Kong Hereditary Breast Cancer Family Registry, Hong Kong SAR, China.
authors.forename: A
authors.initials: A
authors.lastname: Kwong
mesh_terms: D000328:Adult; D000368:Aged; D042241:Early Diagnosis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D064726:Triple Negative Breast Neoplasms / Q000097:blood* / Q000235:genetics / Q000473:pathology
chemical_list: D035683:MicroRNAs; C531408:mirn199 microRNA, human