title: Rare circulating microRNAs as biomarkers of colorectal neoplasia.
abstract: BACKGROUND
  MicroRNAs (miRNAs) are regulatory RNAs, stable in circulation, and implicated in colorectal cancer (CRC) etiology and progression. Therefore they are promising as early detection biomarkers of colorectal neoplasia. However, many circulating miRNAs are highly expressed in blood cells, and therefore may not be specific to colorectal neoplasia.
  
  
  METHODS
  We selected 7 miRNA candidates with previously reported elevated expression in adenoma tissue but low expression in blood cells ("rare" miRNAs), 2 previously proposed as adenoma biomarkers, and 3 implicated in CRC. We conducted a colonoscopy-based case-control study including 48 polyp-free controls, 43 advanced adenomas, 73 non-advanced adenomas, and 8 CRC cases. miRNAs from plasma were quantified by qRT-PCR. Correlations between miRNA expression levels, adjusted for age and sex, were assessed. We used polytomous logistic regression to estimate odds ratios (ORs) and 95% confidence intervals quantifying the association between expression levels of miRNAs and case groups. We also conducted nonparametric receiver operating characteristic (ROC) analyses and estimated area under the curve (AUC).
  
  
  RESULTS
  miRNAs with high expression levels were statistically significantly correlated with one another. No miRNAs were significantly associated with non-advanced or advanced adenomas. Strong (ORs >5) and significant associations with CRC were observed for 6 miRNA candidates, with corresponding AUCs significantly >0.5.
  
  
  CONCLUSIONS
  These candidate miRNAs, assayed by qRT-PCR, are probably unsuitable as blood-based adenoma biomarkers. Strong associations between miRNAs and CRC were observed, but primarily with miRNAs highly expressed in blood cells. These results suggest that rare miRNAs will require new detection methods to serve as circulating biomarkers of adenomas.
authors.affiliation: Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Scott V
authors.initials: SV
authors.lastname: Adams
authors.affiliation: Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Polly A
authors.initials: PA
authors.lastname: Newcomb
authors.affiliation: Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America; School of Public Health, University of Washington, Seattle, Washington, United States of America.
authors.forename: Andrea N
authors.initials: AN
authors.lastname: Burnett-Hartman
authors.affiliation: Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Wurscher
authors.affiliation: School of Medicine, University of Washington, Seattle, Washington, United States of America.
authors.forename: Margaret
authors.initials: M
authors.lastname: Mandelson
authors.affiliation: School of Medicine, University of Washington, Seattle, Washington, United States of America.
authors.forename: Melissa P
authors.initials: MP
authors.lastname: Upton
authors.affiliation: Anatomic Pathology, Group Health Cooperative, Seattle, Washington, United States of America.
authors.forename: Lee-Ching
authors.initials: LC
authors.lastname: Zhu
authors.affiliation: Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America; School of Public Health, University of Washington, Seattle, Washington, United States of America; Centre for Public Health Research, Massey University, Wellington, New Zealand.
authors.forename: John D
authors.initials: JD
authors.lastname: Potter
authors.affiliation: Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Karen W
authors.initials: KW
authors.lastname: Makar
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics*; D016022:Case-Control Studies; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000097:blood* / Q000235:genetics*; D016001:Confidence Intervals; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics*; D008875:Middle Aged; D016017:Odds Ratio; D012372:ROC Curve
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs