title: Potentiality of a triple microRNA classifier: miR-193a-3p, miR-23a and miR-338-5p for early detection of colorectal cancer.
abstract: BACKGROUND
  MicroRNAs (miRNAs) are short, non-coding RNA molecules that act as regulators of gene expression. Circulating blood miRNAs offer great potential as cancer biomarkers. The objective of this study was to correlate the differential expression of miRNAs in tissue and blood in the identification of biomarkers for early detection of colorectal cancer (CRC).
  
  
  METHODS
  The study was divided into two phases: (I) Marker discovery by miRNA microarray using paired cancer tissues (n = 30) and blood samples (CRC, n = 42; control, n = 18). (II) Marker validation by stem-loop reverse transcription real time PCR using an independent set of paired cancer tissues (n = 30) and blood samples (CRC, n = 70; control, n = 32). Correlation analysis was determined by Pearson's test. Logistic regression and receiver operating characteristics curve analyses were applied to obtain diagnostic utility of the miRNAs.
  
  
  RESULTS
  Seven miRNAs (miR-150, miR-193a-3p, miR-23a, miR-23b, miR-338-5p, miR-342-3p and miR-483-3p) have been found to be differentially expressed in both tissue and blood samples. Significant positive correlations were observed in the tissue and blood levels of miR-193a-3p, miR-23a and miR-338-5p. Moreover, increased expressions of these miRNAs were detected in the more advanced stages. MiR-193a-3p, miR-23a and miR-338-5p were demonstrated as a classifier for CRC detection, yielding a receiver operating characteristic curve area of 0.887 (80.0% sensitivity, 84.4% specificity and 83.3% accuracy).
  
  
  CONCLUSIONS
  Dysregulations in circulating blood miRNAs are reflective of those in colorectal tissues. The triple miRNA classifier of miR-193a-3p, miR-23a and miR-338-5p appears to be a potential blood biomarker for early detection of CRC.
authors.affiliation: Department of Surgery, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia. flyong88@yahoo.com
authors.forename: Fung Lin
authors.initials: FL
authors.lastname: Yong
authors.forename: Chee Wei
authors.initials: CW
authors.lastname: Law
authors.forename: Chee Woon
authors.initials: CW
authors.lastname: Wang
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D003110:Colonic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000032:analysis*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; C546818:MIRN193 microRNA, human; C552430:MIRN23a microRNA, human; C532050:MIRN338 microRNA, human; D035683:MicroRNAs