title: Serum miR-21 as a diagnostic and prognostic biomarker in colorectal cancer.
abstract: BACKGROUND
  The oncogenic microRNAs (miRNAs) miR-21 and miR-31 negatively regulate tumor-suppressor genes. Their potential as serum biomarkers has not been determined in human colorectal cancer (CRC).
  
  
  METHODS
  To determine whether miR-21 and miR-31 are secretory miRNAs, we screened expression in medium from 2 CRC cell lines, which was followed by serum analysis from 12 CRC patients and 12 control subjects. We validated expression of candidate miRNAs in serum samples from an independent cohort of 186 CRC patients, 60 postoperative patients, 43 advanced adenoma patients, and 53 control subjects. We analyzed miR-21 expression in 166 matched primary CRC tissues to determine whether serum miRNAs reflect expression in CRC. Patient survival analyses were performed by Kaplan-Meier analyses and Cox regression models. All statistical tests were two-sided.
  
  
  RESULTS
  Although miR-21 was secreted from CRC cell lines and upregulated in serum of CRC patients, no statistically significant differences were observed in serum miR-31 expression between CRC patients and control subjects. In the validation cohort, miR-21 levels were statistically significantly elevated in preoperative serum from patients with adenomas (P < .001) and CRCs (P < .001). Importantly, miR-21 expression dropped in postoperative serum from patients who underwent curative surgery (P < .001). Serum miR-21 levels robustly distinguished adenoma (area under the curve [AUC] = 0.813; 95% confidence interval [CI] = 0.691 to 0.910) and CRC (AUC = 0.919; 95% CI = 0.867 to 0.958) patients from control subjects. High miR-21 expression in serum and tissue was statistically significantly associated with tumor size, distant metastasis, and poor survival. Moreover, serum miR-21 was an independent prognostic marker for CRC (hazard ratio = 4.12; 95% CI = 1.10 to 15.4; P = .03).
  
  
  CONCLUSIONS
  Serum miR-21 is a promising biomarker for the early detection and prognosis of CRC.
authors.affiliation: Gastrointestinal Cancer Research Laboratory, Division of Gastroenterology, Department of Internal Medicine, Charles A. Sammons Cancer Center and Baylor Research Institute, Baylor University Medical Center, Dallas, TX, USA.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Toiyama
authors.forename: Masanobu
authors.initials: M
authors.lastname: Takahashi
authors.forename: Keun
authors.initials: K
authors.lastname: Hur
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nagasaka
authors.forename: Koji
authors.initials: K
authors.lastname: Tanaka
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Inoue
authors.forename: Masato
authors.initials: M
authors.lastname: Kusunoki
authors.forename: C Richard
authors.initials: CR
authors.lastname: Boland
authors.forename: Ajay
authors.initials: A
authors.lastname: Goel
mesh_terms: D000236:Adenoma / Q000175:diagnosis / Q000235:genetics; D000368:Aged; D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000032:analysis / Q000097:blood*; D002277:Carcinoma / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D035683:MicroRNAs / Q000032:analysis / Q000097:blood*; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D012372:ROC Curve; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; C524940:MIRN21 microRNA, human; C534612:MIRN31 microRNA, human; D035683:MicroRNAs