Dynamic liquid biopsy components as predictive and prognostic biomarkers in colorectal cancer

Abstract

Colorectal cancer (CRC) is one of the most common cancers worldwide. The diagnosis, prognosis and therapeutic monitoring of CRC depends largely on tissue biopsy. However, due to tumor heterogeneity and limitations such as invasiveness, high cost and limited applicability in longitudinal monitoring, liquid biopsy has gathered immense attention in CRC. Liquid biopsy has several advantages over tissue biopsy including ease of sampling, effective monitoring, and longitudinal assessment of treatment dynamics. Furthermore, the importance of liquid biopsy is signified by approval of several liquid biopsy assays by regulatory bodies indicating the powerful approach of liquid biopsy for comprehensive CRC screening, diagnostic and prognostics. Several liquid biopsy biomarkers such as novel components of the microbiome, non-coding RNAs, extracellular vesicles and circulating tumor DNA are extensively being researched for their role in CRC management. Majority of these components have shown promising results on their clinical application in CRC including early detection, observe tumor heterogeneity for treatment and response, prediction of metastases and relapse and detection of minimal residual disease. Therefore, in this review, we aim to provide updated information on various novel liquid biopsy markers such as a) oral microbiota related bacterial network b) gut microbiome-associated serum metabolites c) PIWI-interacting RNAs (piRNAs), microRNA(miRNAs), Long non-coding RNAs (lncRNAs), circular RNAs (circRNAs) and d) circulating tumor DNAs (ctDNA) and circulating tumor cells (CTC) for their role in disease diagnosis, prognosis, treatment monitoring and their applicability for personalized management of CRC.

Pragmatic Expectancy on Microbiota and Non-Small Cell Lung Cancer: A Narrative Review

“…Distinct circulating bacterial DNA could distinguish prostate cancer, lung cancer and melanoma patients from healthy populations CHEN [116]. Compared to matched stool and saliva samples, the absolute concentration of circulating free DNA(cfDNA) is low but significantly above the levels detected negative controls [122,123]. Overall, these preliminary data point out a strong potential for liquid biopsy technique to obtain integrative parameters to predict patients' outcomes and, potentially, to predict response to therapies [124].…”

Clinical significance of circulating tumor cells in predicating the outcomes of patients with colorectal cancer

“…The RNA-in situ hybridization 25 technique based on the branched DNA (bDNA) signal amplification system 28 was applied to characterize CTCs. Briefly, bDNA capture probe is used to bind > 30 specific nucleotide sequences called Label Extenders (LEs) of an interested gene, which LE probes bind preamplifiers.…”

“… 24 Third, the CTC detections of solid tumors avoid surgery for evaluating metastasis of cancer. 25 Therefore, monitoring changes of CTCs in cancer patients have a great clinical value in assessing diagnosis, therapy, relapse, metastasis, and prognosis of cancer patients. In our study, the authors aim to investigate the correlation between CTCs profiles and the clinical features of CRC.…”

Liquid Biopsies in Colorectal Liver Metastases: Towards the Era of Precision Oncologic Surgery

“…Cell-derived markers include circulating tumor cells (CTCs), extracellular nucleic acids (i.e., cell-free DNA [cfDNA], mRNA, micro-RNA, long non-coding RNAs, circular RNAs, small non-coding RNAs or PIWI-interacting RNAs [piRNAs]), exosomes as well as glycoproteins and antigens (i.e., CEA, CA19-9, CA-125 etc.). Oral and gut microbiome-associated serum metabolites can also be assessed with liquid biopsies along with tumor-educated platelets (TEPs) [ 7 , 8 ]. cfDNA is a fragment of DNA released into the plasma following apoptosis of normal or tumor cells.…”

“…In contrast, piRNAs are small non-coding nucleotides (usually 24–32 nucleotides in length) that have been associated with several gene regulation mechanisms including transposon silencing, epigenetic programming, DNA rearrangements, mRNA turnover, and translational control [ 8 ]. Exosomes are heterogeneous extracellular vesicles enclosed by a cholesterol-rich lipid bilayer that carry a variety of biologically active molecules that mirror the composition of their originating cells including nucleic acids (DNA, RNA, miRNAs, lncRNA etc), proteins and lipids [ 7 ]. Metagenomic analysis of oral and gut microbiota also has the ability to discriminate cancer versus healthy individuals, given that certain groups of oral pathogens seem to be more abundant in patients with CRC (Fusobacterium, Porphyromonas, and Treponema) and have been postulated to be involved in CRC tumorigenesis [ 7 ].…”