Circulating Tumour DNAs and Non-Coding RNAs as Liquid Biopsies for the Management of Colorectal Cancer Patients

Abstract

Circulating tumour DNAs and non-coding RNAs present in body fluids have been under investigation as tools for cancer diagnosis, disease monitoring, and prognosis for many years. These so-called liquid biopsies offer the opportunity to obtain information about the molecular make-up of a cancer in a minimal invasive way and offer the possibility to implement theranostics for precision oncology. Furthermore, liquid biopsies could overcome the limitations of tissue biopsies in capturing the complexity of tumour heterogeneity within the primary cancer and among different metastatic sites. Liquid biopsies may also be implemented to detect early tumour formation or to monitor cancer relapse of response to therapy with greater sensitivity compared with the currently available protein-based blood biomarkers. Most colorectal cancers are often diagnosed at late stages and have a high mortality rate. Hence, biomolecules as nucleic acids present in liquid biopsies might have prognostic potential and could serve as predictive biomarkers for chemotherapeutic regimens. This review will focus on the role of circulating tumour DNAs and non-coding RNAs as diagnostic, prognostic, and predictive biomarkers in the context of colorectal cancer.

Challenges of Neoantigen Targeting in Lynch Syndrome and Constitutional Mismatch Repair Deficiency Syndrome

“…Recently, the role of circulating tumour DNA and circulating tumour cells as liquid biopsies is being explored as a non-invasive means of predicting metastasis and response to therapy for CRC. For instance, circulating tumour DNA can shed light on the heterogenous tumour landscape and molecular characterisation of the circulating tumour cells can help in the identification of tumour clones resistant to therapy [ 76 ]. This is a promising tool that must be investigated in LS and CMMRD patients as well.…”

Dual Effects of Non-Coding RNAs (ncRNAs) in Cancer Stem Cell Biology

“…The analysis of these so-called liquid biopsies offers the great advantage of detecting and monitoring the molecular identity and makeover of a certain tumor type during the disease course in a minimally invasive and individualized approach, which, in turn, gives the opportunity of precise prognostic and therapeutic interventions [193]. The significance of ncRNA expression analysis in liquid biopsies has already been justified in the diagnosis, prognosis, and recurrence monitoring of several human cancers, including lung [194], and gastrointestinal malignancies [195,196]. Liquid biopsies are further considered to hold great potential in overcoming the limitations of tissue biopsies in identifying the molecular heterogeneity between primary and metastatic tumor sites, as well as in detecting early tumor formation, unresponsiveness to conventional therapies, and disease relapse, which might be attributed to CSC occurrence and their molecular dysregulation at the ncRNA level [195].…”

“…The significance of ncRNA expression analysis in liquid biopsies has already been justified in the diagnosis, prognosis, and recurrence monitoring of several human cancers, including lung [194], and gastrointestinal malignancies [195,196]. Liquid biopsies are further considered to hold great potential in overcoming the limitations of tissue biopsies in identifying the molecular heterogeneity between primary and metastatic tumor sites, as well as in detecting early tumor formation, unresponsiveness to conventional therapies, and disease relapse, which might be attributed to CSC occurrence and their molecular dysregulation at the ncRNA level [195]. However, despite the numerous advantages that liquid biopsy offers, it imposes certain limitations when it comes to ncRNA analysis.…”

“…As an example, the available data on HOTAIR and H19, two of the most well-studied lncRNAs in human malignancies, whose levels have been directly correlated with tumor stage and overall patient survival, are still in their infancy, as it relates to their regulation at multiple levels, their multifaceted actions in tumor initiation and progression, as well as their candidacy as putative biomarkers for cancer diagnosis, prognosis, and therapeutic targeting [231]. However, special attention should be paid to HOTAIR when its expression in liquid biopsy is used for diagnostic purposes, because increased HOTAIR levels in blood have been associated with different types of human malignancies that, in contrast to tissue analysis, can lead to misdiagnosis [195,232,233].…”