Table 2 Merits and Demerits of CTC-based methods, clinical methods and other biomarkers

CTCs

Immunoaffinity-based

Capture cells of specific phenotypes with relatively high specificity, high purity;

Overcome the heterogeneity of physical characteristic

Lack of broad-spectrum specific biomarkers;

Affect cell viability, downstream phenotype identification and molecular analysis;

High cost, low throughput

Biophysical Properties-based

Good cell integrity and viability;

Not restricted by cell surface markers;

Low cost, high throughput

Low specificity and purity;

Significant difference in cell size lead to the omission of small CTTs

Commonality

Low-risk, Low-invasive method for continuous sample acquisition;

Real-time (earlydiagnosis, predict metastasis or recurrence, monitor treatment response);

Live cells, morphological and molecular characterization (precision medicine);

In vitro culture, drug resistance and drug sensitivity cell experiments

Targeted cells are scarce;

Technical limitations (sensitivity and specificity);

Lack of uniform standards (cut-off value, detection time, etc.)

Heterogeneity;

Lack of large-scale prospective trials

Clinical Methods

Medical imaging

Mature, standardized;

Non-invasive, dynamically monitor the morphological changes of lesions;

Insufficient sensitivity;

Not in-time;

The nature of some lesions is not clear

Pathological

Mature, standardized;

High accuracy;

Immunohistochemical staining, genetic testing, in vitro cell culture, etc.

Invasive injury (local reaction, infection, dissemination and metastasis, etc.);

Some patients cannot undergo tissue biopsy (location, size, general condition, etc.);

Heterogeneity (time and space)

Tumor biomarkers

Easy access to samples;

Dynamic monitoring of tumor changes and treatment response

High false positive and false negative rate;

Poor specificity

Other biomarkers

ctDNA

Relatively mature technologies (compared with CTCs);

Short half-life time;

More sensitive to tumor status;

Comprehensive molecular information of tumor

DNA fragments from necrotic or apoptotic cells, cannot represent living tumor cells;

Only provide genetic information;

Low gene mutation abundance, poor sensitivity

Extracellular Vesicles

Large quantity, easy to enrich (compared with CTCs);

Extracellular vesicles can prevent internal nucleic acid substances from being degraded, high stability

Immature technologies (isolation, purification, enrichment of internal specific markers, etc.)

microRNA

Closely related to cell metabolism under physiological and pathological conditions

Immature technologies, few related research