Table 1.

Comparison of different circulating biomarkers.

Marker	Pros	Cons	References
Circulating tumor cells	Can reflect tumor morphology and pathological identification	Very rare	[23,26,67,68,69,70,71]
	Prognostic indicator of disease	Downstream assays may be affected by blood cells
	May represent tumor heterogeneity
	Can also be used for genetic analysis such as gene expression profiling or mutation analysis
Circulating RNA	May provide tissue-specific information	Multiple miRNA signatures required to provide clinical utility	[36,37,40,42,43]
	May provide patient-specific response	Tumor-specific signatures may be indistinguishable from other signals
		miRNA may be affected by hemolysis
Circulating proteins	Inform dynamic changes occurring in cell	Constant modification of proteins not reflective of a specific signature	[47,60]
	Inform changes caused to microenvironment	Difficult to detect very low amounts of protein
Circulating DNA	Monitor treatment response in patients	Dying cells can contaminate samples	[26,66,71,72]
		Difficult to differentiate between cell free DNA and circulating tumor DNA