title: Plasma miR-21: a potential diagnostic marker of colorectal cancer.
abstract: OBJECTIVE
  The main objective of this study was to investigate the potential use of circulating microRNAs (miRNAs) as biomarkers of sporadic colorectal cancer (CRC).
  
  
  BACKGROUND
  CRC, a leading cause of death, is curable if detected early. There is an unmet need for an accurate, noninvasive biomarker of CRC. MiRNAs are non-protein-coding RNAs regulating gene expression that play a role in CRC development.
  
  
  METHODS
  Levels of 380 miRNAs were determined using microfluidic array technology (Applied Biosystems) in a "training" set of 30 CRC patients from whom cancer and adjacent normal tissue were collected. The 4 most dysregulated miRNAs (P < 0.05, false discovery rate (FDR): 10%) were then validated in a second blinded "test" set of 16 CRC patients from whom cancer and normal adjacent tissue had been collected. Validated tissue miRNAs were then evaluated in a plasma "test" set consisting of 30 CRC patients and 30 individuals without CRC. The most dysregulated tissue miRNAs were then validated in an independent new plasma test set consisting of 20 CRC patients with 20 age-, -, and race-matched subjects without CRC.
  
  
  RESULTS
  Nineteen of 380 miRNAs were dysregulated in CRC tissue in the tissue "training" set (P < 0.05, FDR: 10%). The 2 most upregulated (miR-31; miR-135b) and most downregulated (miR-1; miR-133a) miRNAs identified CRC in our "test" set with 100% sensitivity and 80% specificity. MiR-31 was more upregulated in stages III and IV compared with stages I and II (P < 0.05). In the "plasma" group, miR-21 differentiated CRC patients from controls with 90% specificity and sensitivity.
  
  
  CONCLUSIONS
  Plasma miRNAs provide reliable and noninvasive markers for CRC. Plasma miR-21 warrants study in larger cohorts. It seems uniquely promising as a plasma biomarker for CRC.
authors.affiliation: Price Institute of Surgical Research and the Section of Colorectal Surgery, Hiram C. Polk Jr MD Department of Surgery, University of Louisville School of Medicine, Louisville, KY 40292, USA.
authors.forename: Ziad
authors.initials: Z
authors.lastname: Kanaan
authors.forename: Shesh N
authors.initials: SN
authors.lastname: Rai
authors.forename: M Robert
authors.initials: MR
authors.lastname: Eichenberger
authors.forename: Henry
authors.initials: H
authors.lastname: Roberts
authors.forename: Bobby
authors.initials: B
authors.lastname: Keskey
authors.forename: Jianmin
authors.initials: J
authors.lastname: Pan
authors.forename: Susan
authors.initials: S
authors.lastname: Galandiuk
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood / Q000378:metabolism*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation; D005260:Female; D005819:Genetic Markers; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000378:metabolism*; D008875:Middle Aged; D009367:Neoplasm Staging; D012680:Sensitivity and Specificity; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D005819:Genetic Markers; C544547:MIRN1 microRNA, human; C548234:MIRN133 microRNA, human; C544965:MIRN135 microRNA, human; C524940:MIRN21 microRNA, human; C534612:MIRN31 microRNA, human; D035683:MicroRNAs