Circulating cell-free nucleic acids as biomarkers in colorectal cancer screening and diagnosis

ABSTRACT

Screening methods for the most frequent diagnosed malignant tumor, colorectal cancer (CRC), have limitations. Circulating cell-free DNA (cfDNA) analysis came into focus as a potential screening test for CRC. Detection of epigenetic and genetic alterations of cfDNA as DNA methylation or DNA mutations and related ribonucleic acids may improve cancer detection based on unique, CRC-specific patterns. In this review the authors summarize the CRC-specific nucleic acid biomarkers measured in peripheral blood and their potential as screening markers. Detection of DNA mutation has inadequate sensitivity; however, methylated DNA can be established with higher sensitivity from CRC plasma samples. The ribonucleic acid based miRNA studies represented higher sensitivity for CRC as compared with mRNA studies. Recently, isolation of cfDNA has become automated, highly reproducible and a high throughput method. With automated possible diagnostic tools, a new approach may be available for CRC screening as liquid biopsy.

KEYWORDS:

• Colorectal cancer
• screening
• circulating cell-free DNA
• DNA genetic alterations
• RNA expression alterations

Key issues

• Current screening methods for CRC have limitations such as being invasive, requiring expensive techniques, and having inadequate sensitivity and specificity.

• Circulating nucleic acids, such as cfDNA, miRNA, and long noncoding RNA (lncRNA), detected in peripheral blood may be valuable biomarkers for cancer.

• Epigenetic changes can occur early in oncogenesis and are detectable in circulating nucleic acids.

• Blood-based molecular markers may be used not just for screening but for follow-up monitoring as well.

Acknowledgments

The authors thank Theo deVos the help, scientific comments and support our review paper.

Financial & competing interests disclosure

This study was supported by the Hungarian Scientific Research Fund (OTKA-K111743 grant). The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.