MicroRNAs as potential liquid biopsy biomarkers in colorectal cancer: A systematic review

Abstract

Emerging evidence has demonstrated the feasibility of circulating miRNAs as robust non-invasive biomarkers for the diagnosis in colorectal cancer. The use of circulating miRNAs for the early detection of colorectal cancer (CRC) is of particular interest as it can offer a potential complementary approach to screening colonoscopy. However, the development of circulating miRNAs as "liquid biopsy" biomarkers for development into clinical screening tests has been hampered by several issues. In this article, we summarize the status of this field for the clinical utilization of miRNA biomarkers as liquid biopsies in colorectal cancer (CRC) and discuss their applications as screening tests for patients with colorectal adenoma (CRA) and CRC. Herein, we undertook a systematic search for citations in PubMed and the Cochrane Database from January 1, 2002 through December 31, 2017 as electronic sources for this study. All published studies were screened with no restriction on language, date, or country. We used database-specific combinations of the following index terms and text words, including: microRNA, colorectal cancer, serum, plasma, and exosomes. Based upon these searches, we summarize the progress and salient features of the current state of knowledge of miRNA diagnostic biomarkers in CRC, and focuses on the articles that attempt to optimize ideal methodologies to further advance their as liquid biopsies for clinical use. We conclude that the field of noncoding RNAs, particularly for the clinical use of miRNAs as liquid biopsy assays is maturing rapidly, and it is highly promising that these genomic signatures will likely be developed into clinically-viable tests for the early detection and clinical management of patients with colorectal cancer in the not so distant future.

Keywords: Biomarker; Colorectal cancer; Diagnosis; MicroRNA; Screening.

Figure 1.. Systematic literature search flow chart

Figure 2.. The biogenesis of extracellular miRNAs and their use as liquid biopsy biomarkers in CRC.

There are several opportunities for the development of an ideal screening test for CRC. The challenges for an optimal test include minimally invasive access to appropriate liquid specimens, a simple test with high sensitivity and specificity, and demonstrated improved performance over conventional screening tests (fecal immunochemical tests, fecal DNA, etc). Circulating miRs may provide this opportunity. After miRNA biogenesis in the nucleus and cytoplasm, miRNAs are released from tumor cells and are stable in extracellular spaces in various forms, such as exosomes, apoptotic bodies, shed microvesicles, high density lipoprotein particles, or Ago-2 bounded forms. The production of large numbers of miRNA molecules by tumor cells provides the best opportunity to detect asymptomatic cancer. MiRNA dysregulation measured in feces and blood might be exploited for use as non-invasive biomarkers to identify patients with CRAs and early CRCs.