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
| Â | 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 |