title: Circulating miR-18a in plasma contributes to cancer detection and monitoring in patients with gastric cancer.
abstract: BACKGROUND
  Recently, circulating microRNAs have been reported to be stably detectable in plasma/serum and to function as potent non-invasive biomarkers in various cancers. We hypothesized that miR-18a could contribute to a novel plasma biomarker in patients with gastric cancer (GC).
  
  
  METHODS
  We focused on miR-18a, which is a component of miR-17-92 cluster and has been reported as highly expressed in GC tissues. The study involved three steps: (1) confirmation of the higher miR-18a expression in primary GC tissues and GC cell lines than in normal gastric tissues and a fibroblast cell line; (2) evaluation of the plasma miR-18a assay using quantitative RT-PCR by comparing 104 GC patients and 65 healthy volunteers; (3) evaluation of monitoring tumor dynamics by the plasma miR-18a assay.
  
  
  RESULTS
  (1) The miR-18a expressions were significantly higher in GC tissues than in normal gastric tissues (P = 0.0286) and higher in all examined GC cell lines than in the fibroblast cell line. (2) The plasma miR-18a concentrations were significantly higher in GC patients than in healthy controls (P < 0.0001). The value of the area under the receiver-operating characteristic curve was 0.8059. (3) The plasma miR-18a levels were significantly reduced in postoperative samples compared to in preoperative samples (P = 0.0002). In an miR-18a overexpressing cell line, the miR-18a concentration of cultured medium increased in both cell number and time-course dependent manners, suggesting microRNA might be released from cancer cells into the surrounding environment.
  
  
  CONCLUSIONS
  Circulating miR-18a could be a useful biomarker for screening GC and monitoring tumor dynamics.
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: Masahiro
authors.initials: M
authors.lastname: Tsujiura
authors.forename: Shuhei
authors.initials: S
authors.lastname: Komatsu
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ichikawa
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shiozaki
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Konishi
authors.forename: Hiroki
authors.initials: H
authors.lastname: Takeshita
authors.forename: Ryo
authors.initials: R
authors.lastname: Moriumura
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nagata
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Kawaguchi
authors.forename: Shoji
authors.initials: S
authors.lastname: Hirajima
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Arita
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Fujiwara
authors.forename: Kazuma
authors.initials: K
authors.lastname: Okamoto
authors.forename: Eigo
authors.initials: E
authors.lastname: Otsuji
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D016022:Case-Control Studies; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D055088:Early Detection of Cancer; D005260:Female; D005347:Fibroblasts; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000235:genetics* / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; C522576:MIRN18A microRNA, human; D035683:MicroRNAs