Circulating Nucleic Acids in Colorectal Cancer: Diagnostic and Prognostic Value

Abstract

Colorectal cancer (CRC) is the third most prevalent cancer in the world and the fourth leading cause of cancer-related mortality. DNA (cfDNA/ctDNA) and RNA (cfRNA/ctRNA) in the blood are promising noninvasive biomarkers for molecular profiling, screening, diagnosis, treatment management, and prognosis of CRC. Technological advancements that enable precise detection of both genetic and epigenetic abnormalities, even in minute quantities in circulation, can overcome some of these challenges. This review focuses on testing for circulating nucleic acids in the circulation as a noninvasive method for CRC detection, monitoring, detection of minimal residual disease, and patient management. In addition, the benefits and drawbacks of various diagnostic techniques and associated bioinformatics tools have been detailed.

Figure 1

Diagnosis of CRC utilizing circulating tumor nucleic acids. According to a robust, sensitive, and specific noninvasive screening associated with a panel of elevated ctDNA and ctRNA signature expression, it is conceivable that these blood biomarkers can be used for early CRC detection.

Figure 2

CRC prognosis and treatment response based on circulating tumor nucleic acids throughout the duration of the initial CRC diagnosis, ctDNA, and ctRNA levels were elevated. Then, ctDNA and ctRNA rapidly disappear from the peripheral blood after surgery, but they rise again, resulting in an early relapse. In the absence of tumor biopsy specimens, they can also be used for cancer molecular tracking to detect MRD, monitoring therapeutic response, and predicting the risk of cancer recurrence. It was also correlated with the worst prognosis in advanced stages of colorectal cancer. In addition, there is evidence that ctDNA predicted future radiographic relapse owing to a small decrease and increase in the blood extents, respectively, after adjuvant therapy.

Figure 3

The clinical significance of tumor-derived circulating nucleic acids in advanced colorectal cancer. This diagram depicts the most important clinical applications of liquid biopsies. These include tumor genotyping and epigenotyping in the diagnosis of CRC, evaluating drug response, tracing minimal residual disease, and observing clonal evolution.