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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





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


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


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


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


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


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