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. 2021 Apr 16;11:634316. doi: 10.3389/fonc.2021.634316

Table 1.

Summary of advantages and limitations in LC diagnosis according to liquid biopsy-based biomarker.

Biomarkers Advantages Limitations References
cfDNA

  • Increased in cancer patients comparing to healthy individuals;

  • Genetic and epigenetic alterations reflect those of the original tumor;

  • Representation of tumor heterogeneity and dynamics;

  • Highly sensitive assays available (PCR, NGS).

  • Markedly diluted compared to germline circulating DNA;

  • Positively correlates with tumor size and staging;

  • Increased in some benign or premalignant conditions;

  • High costs.

 (16, 17–18)
CTC

  • Allows morphologic analysis and tumor molecular characterization;

  • Correlates with prognosis;

  • Emerging enrichment and characterization techniques.

  • No validated assay;

  • Rare in bloodstream and surrounded by blood cells;

  • Epithelial to mesenchymal transition with loss of epithelial-specific markers;

  • Role in cancer spreading still to be clarified.

 (17, 19, 20)
miRNA

  • Different profiles among early-stage cancer patients;

  • Stable in most types of body fluids (e.g. respiratory samples);

  • Released by several structures (e.g. exosome, TEPs).

  • Commercial kits available for collection.

  • High variability, according to patients and technologies, requiring normalization methods;

  • Quantification and detection methods need to be validated

  • Unspecific for a cancer type.

 (21–22)
Exosomes

  • Contains several types of biomarkers such as proteins and nucleic acids;

  • Increased in lung cancer patients;

  • Stable and accessible in most types of body fluids;

  • Commercial kits available for isolation.

  • The extraction approach, detection and characterization methods are challenge and require standardization;

  • High costs

 (23–24)
TEP

  • Platelet mRNA profile is distinct in cancer patients;

  • Abundant;

  • Easily isolated;

  • Acquire specific RNA from tumor cells reflecting its genetic alterations;

  • Dynamic mRNA repertoire due to short life-span.

  • No validated assay nor standardized approach;

  • Reproducibility;

  • Detection techniques not widely available;

  • Time consuming and requires extensive computational resources.

 (25–26)