title: Circulating microRNAs in plasma of patients with oesophageal squamous cell carcinoma.
abstract: BACKGROUND
  Several recent studies demonstrated that microRNAs (miRNAs) are stably detectable in plasma/serum. We hypothesised that plasma miRNAs concentrations contributed to potential biomarkers in patients with oesophageal squamous cell carcinoma (ESCC).
  
  
  METHODS
  We selected three oncogenic miRNAs (miR-21, miR-184, miR-221) and one tumour suppressive miRNA (miR-375), which are frequently reported in squamous cell carcinoma, as candidate targets for this plasma miRNA assay. This study was divided into three steps: (1) Determination of appropriate plasma miRNAs in preliminary tests. (2) Evaluation of whether the plasma miRNA assays could monitor tumour dynamics. (3) Validation study on the clinical application of plasma miRNA assays in 50 ESCC patients and 20 healthy volunteers.
  
  
  RESULTS
  (1) In preliminary tests, the plasma level of miR-21 was significantly higher (P=0.0218) and that of miR-375 (P=0.0052) was significantly lower in ESCC patients than controls. (2) The high plasma miR-21 levels reflected tumour levels in all cases (100%). The plasma level of miR-21 was significantly reduced in postoperative samples (P=0.0058). (3) On validation analysis, the plasma level of miR-21 tended to be higher in ESCC patients (P=0.0649), while that of miR-375 was significantly lower (P<0.0001) and the miR-21/miR-375 ratio was significantly higher (P<0.0001) in ESCC patients than in controls. The value of the area under the receiver-operating characteristic curve (AUC) was 0.816 for the miR-21/miR-375 ratio assay. Patients with a high plasma level of miR-21 tended to have greater vascular invasion (P=0.1554) and to show a high correlation with recurrence (P=0.0164).
  
  
  CONCLUSIONS
  Detection of circulating miRNAs might provide new complementary tumour markers for ESCC.
authors.affiliation: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
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: M
authors.initials: M
authors.lastname: Tsujiura
authors.forename: R
authors.initials: R
authors.lastname: Morimura
authors.forename: H
authors.initials: H
authors.lastname: Nagata
authors.forename: T
authors.initials: T
authors.lastname: Kosuga
authors.forename: D
authors.initials: D
authors.lastname: Iitaka
authors.forename: H
authors.initials: H
authors.lastname: Konishi
authors.forename: A
authors.initials: A
authors.lastname: Shiozaki
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*; D002294:Carcinoma, Squamous Cell / Q000097:blood* / Q000175:diagnosis / Q000235:genetics; D016022:Case-Control Studies; D004938:Esophageal Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000235:genetics; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000175:diagnosis / Q000235:genetics; D011379:Prognosis; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; C534424:MIRN184 microRNA, human; C524940:MIRN21 microRNA, human; C525709:MIR221, human; C540933:MIRN375 microRNA, human