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Table 1 Comparison of advantages and limitations of analytes found in liquid biopsy samples

From: Current status of ctDNA in precision oncology for hepatocellular carcinoma

  Advantages Limitations
CTCs Available for analysis of splice variants, information at single-cell level and functional assays regard to genomics, transcriptomics, metabolomics and proteomics
Capable of subsequent culture and further biological analyses
Useful for screening new drug, drug resistance and treatment test
Identifying tumor patients with minimal residual disease who are at risk of recurrence
Low abundance in biofluids and difficult in capture and isolation
Lack of consensus on isolation and detection methods makes comparison of data from different platforms challenging
Expression loss of epithelial cell surface markers during the epithelial-to-mesenchymal transition process
High degree of heterogeneity
ctDNA Providing a comprehensive overview of genomic spectrum respond to different regions of the tumor
Improvements in technology enabled greater sensitivity of analytical assay
Short half-life of ctDNA allowing for real-time monitoring of cancer
More precise with respect to clinical correlations
Time-consuming and highly cost
Most of the emerging assays have not yet been clinically validated
Genetic information only, not information on the body site of the cancer concerned
miRNA With broad application prospects because of miRNAs are involved in many pathogenic processes
High specificity and reproducibility
A good candidate for cancer prevention because of patients with precancerous lesions also showing an altered pattern of circulating miRNAs
The rupture of erythrocytes and platelet containing miRNAs may influence detection levels during sample extraction and preparation
Co-morbidities can lead to increased miRNAs and interfere with the detection of cancer-specific miRNA levels
Technical limitation
cfRNA Capable to present the up-to-date snapshot of the transcriptome
Can be used to differentiate cancer subtypes
Be able to detect cancer and trace it back to its origin site
Lack of robustly designed and independently validated biomarker studies.
Low quantity and low quality in biofluids
High variability of cfRNA expression between individuals
EVs Carrying multiple biological information released from parent cells, including proteins, nuclear acids, lipids and metabolites and capable to provide information exchange
EVs are more abundant in plasma/serum compared to CTCs and much more stable in circulation by protection of a lipid membrane compared with cfDNA
Small size and low density make isolation and analysis difficult
High transport and collection requirements
Being interfered by co-morbidities or medical therapy background
Circulating proteins Initial attempts to combine circulating proteins with other analytes was suggested to improve early detection of cancer Only a small number of established protein markers have been applied in clinics
Information about tissue specificity or cancer specificity is largely missing
Very low abundance, high complexity and dynamic nature involved
Metabolites Providing an overview of the physiological state connected with the phenotype
Potentially for differentiating between benign and malignant lesions
Technical limitations
Few relevant studies
  1. Abbreviation: CTCs circulating tumor cells, ctDNA circulating tumor DNA, cfDNA cell free DNA, EVs extracellular vesicles, cfRNA cell free RNA