Table 2.
Comparison of three types of liquid biopsy molecules (CTCs, ctNAs and exosomes)
| Type | Source | Enrichmental or analytical methods | Strength | Limitation |
|---|---|---|---|---|
|
CTCs |
Peripheral blood | Physical property-based methods: tumor cell size 29, 197; biological property-based methods: mesenchymal cell markers, specific chromosomal translocations, specific gene mutation 24, 197 | Non-invasive 29, 197; DNAs, RNAs and proteins can be analyzed and can be used as diagnostic or prognostic biomarkers 29, 197; can be used to evaluate the response to therapy and for early detection of residual and recurrent lesions 29, 197 |
Impact of heterogeneity on various CTC enrichment methods 24; low concentration of CTCs 24; absence of specific markers expressed by sarcoma tumor cells and highly heterogeneous phenotype 24 |
|
ctDNA and
ctRNA |
Serum or plasma | PCR(e.g., conventional RT-qPCR; dPCR; ddPCR); NGS; RNA-seq 16, 58 | Non-invasive 16, 58; Can be used to analyze the tumor molecular heterogeneity; for precision therapeutic decision making based on specific gene mutation; for monitoring tumor burden and prognosis 16, 58; for early detection of emerging chemotherapy resistance 16, 58 |
Sample type and preparation protocols are different in different studies 16, 195; the relation between ctNAs and clinicopathological features is unclear 16, 195; sequencing data require professional bioinformatics analysis 16 |
| Exosomes | Serum, plasma or other body fluids | Ultracentrifugation; density gradient centrifugation; membrane filtration; size exclusion chromatography; microfludic technologies 16, 58 | Non-invasive; abundant in multiple body fluids; exosomes contain DNAs, RNAs and proteins that have diagnostic and prognostic value 16, 58 | The purity of tumor-derived exosomes is different for different isolation methods; identification of the exosomes is difficult due to the lack of specific markers 16, 58 |
Abbreviations: CTCs: circulating tumor cells; ctNAs: circulating tumor nucleic acids, including circulating tumor DNA(ctDNA), specific gene transcripts, non-coding RNA; NGS: next generation sequence; RT-PCR: real time polymerase chain reaction; dPCR: digital polymerase chain reaction; ddPCR: droplet digital polymerase chain reaction.