TABLE 1.

Strengths and limitations of applying ctDNA, CTC, and non-coding RNA (Jia et al., 2017; Nordgård et al., 2018; Normanno et al., 2018; Burz and Rosca, 2019; Pantel and Alix-Panabières, 2019).

	Strengths	Limitations
ctDNA	Well-established methods (e.g., NGS, ddPCR, ARMS, BEAMing, etc.) for detection and data analysis High sensitivity Identifying molecular and genomic features (e.g., bMSI, bTMB, DNA methylation) Analyzing cancer origin Predicting drug effects and acquired resistance Postoperative detection of minimal residual disease Monitoring metastatic process and disease progression	Discrimination of ctDNA in ctDNA pool Very low ctDNA abundance Impossibility of functional assays Impossibility of RNA and protein analysis Limited methodological standardization False-positives in certain high-sensitivity methods False-negatives due to the extremely low ctDNA level or interindividual variations of ctDNA abundance
CTC	Identifying morphological and molecular features Analyzing DNA, RNA, and protein profiles Functional assays in vitro or in vivo Analyzing cancer origin Utility as a prognostic or predictive marker Monitoring metastatic process and disease progression	Low CTC abundance CTC fragility Heterogeneity of CTC populations Limited methodological standardization False-positives due to normal cells from gastrointestinal inflammatory diseases False-negatives due to the difficulty of CTC isolation and tumor metastasis
Circulating non-coding RNA	Analyzing RNA expression profiles Potential marker for diagnosis, prognostic, and prediction	Low abundance and instability Difficult extraction Limited methodological standardization Requirement for more clinical evidences

ctDNA, circulating tumor DNA; CTC, circulating tumor cells.