title: Circulating microRNAs as specific biomarkers for breast cancer detection.
abstract: BACKGROUND
  We previously showed microRNAs (miRNAs) in plasma are potential biomarkers for colorectal cancer detection. Here, we aimed to develop specific blood-based miRNA assay for breast cancer detection.
  
  
  RESULTS
  TaqMan-based miRNA profiling was performed in tumor, adjacent non-tumor, corresponding plasma from breast cancer patients, and plasma from matched healthy controls. All putative markers identified were verified in a training set of breast cancer patients. Selected markers were validated in a case-control cohort of 170 breast cancer patients, 100 controls, and 95 other types of cancers and then blindly validated in an independent set of 70 breast cancer patients and 50 healthy controls. Profiling results showed 8 miRNAs were concordantly up-regulated and 1 miRNA was concordantly down-regulated in both plasma and tumor tissue of breast cancer patients. Of the 8 up-regulated miRNAs, only 3 were significantly elevated (p<0.0001) before surgery and reduced after surgery in the training set. Results from the validation cohort showed that a combination of miR-145 and miR-451 was the best biomarker (p<0.0001) in discriminating breast cancer from healthy controls and all other types of cancers. In the blind validation, these plasma markers yielded Receiver Operating Characteristic (ROC) curve area of 0.931. The positive predictive value was 88% and the negative predictive value was 92%. Altered levels of these miRNAs in plasma have been detected not only in advanced stages but also early stages of tumors. The positive predictive value for ductal carcinoma in situ (DCIS) cases was 96%.
  
  
  CONCLUSIONS
  These results suggested that these circulating miRNAs could be a potential specific biomarker for breast cancer screening.
authors.affiliation: Department of Surgery, The University of Hong Kong, Hong Kong, China. ngko@hku.hk
authors.forename: Enders K O
authors.initials: EK
authors.lastname: Ng
authors.forename: Rufina
authors.initials: R
authors.lastname: Li
authors.forename: Vivian Y
authors.initials: VY
authors.lastname: Shin
authors.forename: Hong Chuan
authors.initials: HC
authors.lastname: Jin
authors.forename: Candy P H
authors.initials: CP
authors.lastname: Leung
authors.forename: Edmond S K
authors.initials: ES
authors.lastname: Ma
authors.forename: Roberta
authors.initials: R
authors.lastname: Pang
authors.forename: Daniel
authors.initials: D
authors.lastname: Chua
authors.forename: Kent-Man
authors.initials: KM
authors.lastname: Chu
authors.forename: W L
authors.initials: WL
authors.lastname: Law
authors.forename: Simon Y K
authors.initials: SY
authors.lastname: Law
authors.forename: Ronnie T P
authors.initials: RT
authors.lastname: Poon
authors.forename: Ava
authors.initials: A
authors.lastname: Kwong
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood* / Q000175:diagnosis*; D016022:Case-Control Studies; D015331:Cohort Studies; D055088:Early Detection of Cancer / Q000379:methods; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D011237:Predictive Value of Tests; D012372:ROC Curve
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs