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

ABSTRACT

Introduction: Screening methods for one of the most frequently diagnosed malignancy, colorectal cancer (CRC), have limitations. Circulating cell-free nucleic acids (cfNA) hold clinical relevance as screening, prognostic and therapy monitoring markers.

Area covered: In this review, we summarize potential CRC-specific cfNA biomarkers, the recently developed sample preparation techniques, their applications, and pitfalls.

Expert opinion: Automated extraction of cfDNA is highly reproducible, however, cfDNA yield is less compared to manual isolation. Quantitative and highly sensitive detection techniques (e.g. digital PCR, NGS) can be applied to analyze genetic and epigenetic changes. Detection of DNA mutations or methylation in cfDNA and related altered levels of mRNA, miRNA, and lncRNA may improve early cancer recognition, based on specific, CRC-related patterns. Detection of cfDNA mutations (e.g. TP53, KRAS, APC) has limited diagnostic sensitivity (40–60%), however, methylated DNA including SEPT9, SFRP1, SDC2 can be applied with higher sensitivity (up to 90%) for CRC. Circulating miRNAs (e.g. miR-21, miR-92, miR-141) provide comparably high sensitivity for CRC as the circulating tumor cell mRNA markers (e.g. EGFR, CK19, CK20, CEA). Automation of cfNA isolation coupled with quantitative analysis of CRC-related, highly sensitive biomarkers may enhance CRC screening and early detection in the future.

KEYWORDS:

• Colorectal cancer
• screening
• circulating cell-free nucleic acids
• DNA mutation
• epigenetic alterations
• mRNA
• miRNA
• lncRNA

Acknowledgments

The authors thank Ramani Gopal, Ph.D. (2nd Department of Internal Medicine, Semmelweis University, Hungary) for language revision. This study was supported by the NVKP_16-1-2016-0004 grant of the Hungarian National Research, Development and Innovation Office (NKFIH).

Declaration of interest

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.

No writing assistance was utilized in the production of this manuscript.

Reviewers Disclosure

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.