Table 1.

Comparisons of the advantages and drawbacks of integrated and single liquid biopsy biomarkers.

Clinical stages	Features and Drawbacks of Single TAM			Categories and Advantages of Integrated TAM
		Features	Shortcomings
Early diagnosis	ctDNA	Can detect a minimum of 0.005% abundance of mutant alleles. Its concentration correlates to tumor size and stage 17.	Limited sensitivity in the detection of non-necrotic cancers 78.	Elementary integration: Structure-based IsoPSATM assay based on PSA measurement, provides a net benefit against other protocols 26. Meanwhile combination of ten exosomal miRNAs yielded 0.99 sensitivity and 1.00 specificity in detection of early-stage ovarian cancer 9. Intermediate integration: exoRNA-ctDNA integration in the plasma of NSCLC patients improved the sensitivity of EGFR mutation detection from 26% to 74% 37. Advanced integration: CancerSEEK combines ctDNA and CP with machine learning and has achieved 98% sensitivity and a <1% false positive rate for the detection of five cancer types 7.
	CP	Convenient detection	Less informative about tumor mutations79.
	EVs	Exosomes containing uncontaminated DNA, RNA and proteins provide outstanding specificity and sensitivity 21.	Lack of spatial and temporal tumor heterogeneity.
	CTCs	A high concentration (≥5 CTCs/7.5 mL) indicates higher risk of early cancer progression.	CTCs in the blood are rare.
Therapy management (Postope-ration and prognosis	ctDNA	Short circulating time contributes to the monitoring of tumor evolution in real-time 80.	Less efficient in analyzing drug-resistance mechanisms.	Elementary integration: DNA sequencing mutations in exosomes is reliable in monitoring pancreatic cancer to establish curative surgical therapy (41). Intermediate integration: exoRNA-ctDNA integration increases the sensitivity of EGFR mutations detection in plasma to monitor responses to therapy 37. CEA-ctDNA integration predicts recurrence after adjuvant chemotherapy 81. Advanced integration: Combination of liquid biopsy (biological information from CTCs) and MRI (anatomy and physiological information) provides additional information than either modality alone 82.
	CTCs	Key checkpoints in metastasis. Strong prognostic factor for overall survival in patients. Assist in the establishment of a CTC-derived xenograft (CDX) model to search for druggable targets 83.	Inefficiency in discovering intratumoral heterogeneity Inefficiency clonal evolution of cancers after targeted therapy.
	EVs	Exosomes miRNA profiles can predict survival after therapy 84 .	Therapy-induced tumor heterogeneity and EV diversity.