title: Circulating plasma microRNAs as a screening method for detection of colorectal adenomas.
abstract: BACKGROUND
  MicroRNAs (miRNAs) are small non-coding RNA molecules. Reduced or increased levels of specific miRNAs are observed in colon and other cancers, supporting their role in carcinogenesis. Detection of colorectal polyps is the cornerstone of the Bowel Cancer Screening Programme in the UK. However, uptake of screening nationally remains under 60%. We aimed to see whether circulating plasma miRNAs can be used to screen for patients with colorectal polyps, adenomas, or both.
  
  
  METHODS
  Blood samples were taken from patients from the Bowel Cancer Screening Programme (asymptomatic but faecal occult blood testing [FOBt] positive). Plasma RNA was extracted, target miRNAs (19a, 98, 146b, 186, 191, 222*, 331-5p, 452, 625, 664, 1247) were identified on pooled case miRNA assay cards, and miRNA fraction was quantified by quantitative RT-PCR assay. Results were compared with endoscopy reports and with histology of any polyps identified and removed. Analysis was done with Excel (2011) and SPSS (version 20) software.
  
  
  RESULTS
  210 patients were included (117 with polyps, 12 with cancer, 81 healthy controls [FOBt positive]). The miRNA panel showed significant differences in expression (on t testing) for patients compared with controls for those with polyps, cancer, or both (miR-19a, p=0·0184; miR-98, p=0·0206; miR-146b, p=0·0029; miR-186, p=0·0006; miR-62,5 p=0·0008), polyps (miR-19a, p=0·0233; miR-98, p=0·0224; miR-146b, p=0·003; miR-186, p=0·0004; miR-625, p=0·001), adenomas (miR-19a, p=0·0339; miR-98, p=0·0266; miR-146b, p=0·0045; miR-186, p=0·0008; miR-625, p=0·0049), multiple adenomas (both sides of colon; miR-146b, p=0·0194; miR-186, p=0·0226; miR-625, p=0·0013), and right-sided adenomas (miR-98, p=0·031; miR-146b, p=0·0076; miR-186, p=0·0041; miR-331-5p, p=0·0142; miR-625, p=0·0049). Receiver operating characteristic analysis showed sensitivity of 60% or more, and specificity of 86% or more for men with polyps, men with adenomas, all patients with haemorrhoids or diverticulosis and polyps, and all patients with haemorrhoids or diverticulosis and adenomas.
  
  
  CONCLUSIONS
  The target miRNAs that we identified showed significant differences in expression levels for patients with polyps and patients with adenomas from controls. Use of this panel has potential as a screening test.
  
  
  BACKGROUND
  Bowel Disease Research Foundation.
authors: University of Leicester, University Hospitals Leicester, Leicester, UK. Electronic address: ajaymarkverma@gmail.com.
authors: Ajay M
authors: AM
authors: Verma
authors: University of Leicester, Leicester, UK.
authors: Maleene
authors: M
authors: Patel
authors: University of Leicester, University Hospitals Leicester, Leicester, UK.
authors: Muhammad Imran
authors: MI
authors: Aslam
authors: University of Leicester, University Hospitals Leicester, Leicester, UK.
authors: John
authors: J
authors: Jameson
authors: University of Leicester, Leicester, UK.
authors: James Howard
authors: JH
authors: Pringle
authors: University of Leicester, University Hospitals Leicester, Leicester, UK.
authors: Peter
authors: P
authors: Wurm
authors: University of Leicester, University Hospitals Leicester, Leicester, UK.
authors: Baljit
authors: B
authors: Singh