microRNA-221 and microRNA-18a identification in stool as potential biomarkers for the non-invasive diagnosis of colorectal carcinoma

Br J Cancer. 2014 Oct 28;111(9):1765-71. doi: 10.1038/bjc.2014.484. Epub 2014 Sep 18.

Abstract

Background: The detection of microRNA (miRNA) dysregulation in stool is a novel approach for the diagnosis of colorectal carcinoma (CRC). The aim of this study is to investigate the use of miR-221 and miR-18a in stool samples as non-invasive biomarkers for CRC diagnosis.

Methods: A miRNA expression array containing 667 miRNAs was performed to identify miRNA dysregulation in CRC tissues. We focused on miR-221 and miR-18a, two significantly upregulated miRNAs which were subsequently verified in 40 pairs of CRC tissues and 595 stool samples (198 CRCs, 199 polyps and 198 normal controls).

Results: miR-221 and miR-18a were upregulated in the miRNA expression array. miR-221 and miR-18a levels were also significantly higher in 40 CRC tumours compared with their respective adjacent normal tissues. In stool samples, miR-221 and miR-18a showed a significant increasing trend from normal controls to late stages of CRC (P<0.0001). The levels of stool miR-221 and miR-18a were both significantly higher in subjects with stages I+II (miR-221: P<0.0001, miR-18a: P<0.0001) and stages III+IV of CRC (miR-221: P=0.0004, miR-18a: P<0.0001) compared with normal controls. The AUC of stool miR-221 and miR-18a were 0.73 and 0.67 for CRC patients as compared with normal controls, respectively. No significant differences in stool miR-221 and miR-18a levels were found between patients with proximal and distal CRCs. The use of antibiotics did not influence stool miRNA-221 and miRNA-18a levels.

Conclusions: Stool-based miR-221 can be used as a non-invasive biomarker for the detection of CRC.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers, Tumor / genetics*
  • Case-Control Studies
  • Colorectal Neoplasms / diagnosis*
  • Colorectal Neoplasms / genetics*
  • Feces / chemistry*
  • Female
  • Follow-Up Studies
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Prognosis
  • ROC Curve

Substances

  • Biomarkers, Tumor
  • MIRN18 microRNA, human
  • MIRN221 microRNA, human
  • MicroRNAs