The diagnostic efficacy of circulating miRNAs in monitoring the early development of colitis-induced colorectal cancer

J Cell Biochem. 2019 Oct;120(10):16668-16680. doi: 10.1002/jcb.28925. Epub 2019 May 16.

Abstract

Early detection of colorectal cancer and monitoring the progress in colon carcinogenesis stages is essential to reduce mortality. Therefore, there is continuous search for noninvasive biomarkers with high stability and good sensitivity and specificity. miRNAs have attracted attention as promising biomarkers as they are stably expressed in circulation. The aim of our study is to evaluate the aberrant expression of circulating miRNAs during the stepwise progress of colitis-associated colon cancer. This was accomplished through assessing the expression levels of five miRNAs (miR-141, miR-15b, miR-17-3p, miR-21, and miR-29a) in serum and their corresponding tissue samples through the different cycles of colorectal carcinogenesis cascade using the azoxymethane/dextran sulfate sodium murine model. We also compared the diagnostic performance of these selected miRNAs with the conventional tumor biomarkers CEA and CA 19-9. The results of our study revealed that the expression levels of those miRNAs were dynamically changing in accordance with the tumor development state. Moreover, their aberrant expression in serum was statistically correlated with that in tissue. Our data also revealed that serum miR-15b, miR-21, and miR-29a showed the best performance in terms of diagnostic power. Our findings highlight the efficiency of these circulating miRNAs not only for early diagnostics purposes, but also for monitoring progress in the colorectal carcinogenesis process, and therefore encouraging integrating these noninvasive biomarkers into the clinical diagnostic settings beside the traditional diagnostic markers for accurate screening of the early progress of colon carcinogenesis.

Keywords: Noninvasive biomarkers, miR-141; circulating miRNAs, colorectal cancer; miR-17-3p; miR-21; miR-29a; miiR-15b.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Azoxymethane / toxicity
  • Circulating MicroRNA / blood*
  • Colitis* / blood
  • Colitis* / chemically induced
  • Colitis* / complications
  • Colitis* / diagnosis
  • Colorectal Neoplasms* / blood
  • Colorectal Neoplasms* / diagnosis
  • Colorectal Neoplasms* / etiology
  • Dextran Sulfate / toxicity
  • Gene Expression Regulation, Neoplastic*
  • Male
  • Mice
  • Neoplasms, Experimental* / blood
  • Neoplasms, Experimental* / diagnosis
  • Neoplasms, Experimental* / etiology

Substances

  • Circulating MicroRNA
  • Dextran Sulfate
  • Azoxymethane