title: A plasma microRNA panel for detection of colorectal adenomas: a step toward more precise screening for colorectal cancer.
abstract: OBJECTIVE
  The main objective of this study was to investigate the potential use of circulating microRNAs (miRNAs) as biomarkers of colorectal (CR) adenomas.
  
  
  BACKGROUND
  Detection of precancerous lesions such as CR adenoma is a key to reduce CR cancer (CRC) mortality. There is a great need for accurate, noninvasive biomarkers for detection of CR adenoma and CRC. MiRNAs are non-protein-coding RNAs that regulate gene expression. Our prior work investigated the dysregulation of 5 plasma miRNAs in CRC patients. As intended, we undertook a more comprehensive plasma-miRNA screening study in patients with CR adenoma and CRC.
  
  
  METHODS
  We screened for 380 plasma-miRNAs using microfluidic array technology (Applied BioSystems) in a screening cohort of 12 healthy controls, 9 patients with CR adenomas, and 20 patients with CRC. A panel of the most dysregulated miRNAs (P < 0.05, False Discovery Rate: 5%) was then validated in a blinded cohort of 26 healthy controls, 16 patients with large adenomas, and 45 patients with CRC.
  
  
  RESULTS
  A panel of 8 plasma miRNAs (miR-532-3p, miR-331, miR-195, miR-17, miR-142-3p, miR-15b, miR-532, and miR-652) distinguished polyps from controls with high accuracy [area under curve (AUC) = 0.868 (95% confidence interval [CI]: 0.76-0.98)]. In addition, a panel of 3 plasma miRNAs (miR-431, miR-15b, and miR-139-3p) distinguished Stage IV CRC from controls with an [AUC = 0.896 (95% CI: 0.78-1.0)]. Receiver-operating-characteristic curves of miRNA panels for all CRC versus controls and polyps versus all CRC showed AUC values of 0.829 (95% CI: 0.73-0.93) and 0.856 (95% CI: 0.75-0.97), respectively.
  
  
  CONCLUSIONS
  Plasma miRNAs are reliable, noninvasive, and inexpensive markers for CR adenomas. This miRNA panel warrants study in larger cohorts. Plasma-based assays could provide better screening compliance compared to fecal occult blood or endoscopic screening.
authors.affiliation: *Price Institute of Surgical Research and the Section of Colorectal Surgery, Hiram C. Polk Jr MD Department of Surgery †Department of Bioinformatics and Biostatistics, University of Louisville School of Medicine, Louisville, KY.
authors.forename: Ziad
authors.initials: Z
authors.lastname: Kanaan
authors.forename: Henry
authors.initials: H
authors.lastname: Roberts
authors.forename: M Robert
authors.initials: MR
authors.lastname: Eichenberger
authors.forename: Adrian
authors.initials: A
authors.lastname: Billeter
authors.forename: Gairy
authors.initials: G
authors.lastname: Ocheretner
authors.forename: Jianmin
authors.initials: J
authors.lastname: Pan
authors.forename: Shesh N
authors.initials: SN
authors.lastname: Rai
authors.forename: Jeffery
authors.initials: J
authors.lastname: Jorden
authors.forename: Anna
authors.initials: A
authors.lastname: Williford
authors.forename: Susan
authors.initials: S
authors.lastname: Galandiuk
mesh_terms: D000236:Adenoma / Q000097:blood / Q000175:diagnosis*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000097:blood / Q000175:diagnosis*; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012372:ROC Curve; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016037:Single-Blind Method
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs