title: Clinical impact of circulating miR-18a in plasma of patients with oesophageal squamous cell carcinoma.
abstract: BACKGROUND
  Several recent studies demonstrated that microRNAs are stably detectable in plasma/serum. We tested whether miR-18a, which is located in the miR-17-92 cluster and reported to be highly expressed in tissues of oesophageal squamous cell carcinoma (ESCC), served as a plasma biomarker in patients with ESCC.
  
  
  METHODS
  This study was divided into three steps: (1) confirmation of higher miR-18a levels in primary ESCC tissues and cell lines than normal ESCC tissues and a human fibroblast cell line. (2) Evaluation of the plasma miR-18a assay using quantitative RT-PCR by comparing results from 106 consecutive patients with ESCC and 54 healthy volunteers. (3) Evaluation of the assay for monitoring tumour dynamics in patients with ESCC.
  
  
  RESULTS
  (1) Expression of miR-18a was significantly higher in ESCC tissues (P=0.0020) and ESCC cell lines (P=0.0121) than normal tissues and fibroblasts. (2) Plasma concentrations of miR-18a were significantly higher in ESCC patients than healthy volunteers (P<0.0001; ESCC patients vs healthy volunteers (mean±s.d.): 11.77±13.45 vs 0.73±0.54 amol μl(-1)). The value of the area under the receiver-operating characteristic (ROC) curve (AUC) was 0.9449. Furthermore, the ROC curves to detect early ESCC such as pTis-1 and pStage0-I showed AUCs of 0.9479 and 0.9642, respectively. (3) Plasma levels of miR-18a were significantly lower in postoperative samples than preoperative samples (P=0.0076).
  
  
  CONCLUSIONS
  Plasma miR-18a may be a very useful biomarker for cancer detection and the monitoring of tumour dynamics in patients with ESCC.
authors.affiliation: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Hirajima
authors.forename: S
authors.initials: S
authors.lastname: Komatsu
authors.forename: D
authors.initials: D
authors.lastname: Ichikawa
authors.forename: H
authors.initials: H
authors.lastname: Takeshita
authors.forename: H
authors.initials: H
authors.lastname: Konishi
authors.forename: A
authors.initials: A
authors.lastname: Shiozaki
authors.forename: R
authors.initials: R
authors.lastname: Morimura
authors.forename: M
authors.initials: M
authors.lastname: Tsujiura
authors.forename: H
authors.initials: H
authors.lastname: Nagata
authors.forename: T
authors.initials: T
authors.lastname: Kawaguchi
authors.forename: T
authors.initials: T
authors.lastname: Arita
authors.forename: T
authors.initials: T
authors.lastname: Kubota
authors.forename: H
authors.initials: H
authors.lastname: Fujiwara
authors.forename: K
authors.initials: K
authors.lastname: Okamoto
authors.forename: E
authors.initials: E
authors.lastname: Otsuji
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000097:blood* / Q000175:diagnosis / Q000235:genetics; D045744:Cell Line, Tumor; D004938:Esophageal Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics; D011379:Prognosis; D012372:ROC Curve
chemical_list: D014408:Biomarkers, Tumor; C522576:MIRN18A microRNA, human; D035683:MicroRNAs