Biomarkers for hepatocellular carcinoma based on body fluids and feces

Table 1 The major values of circulating tumor cells and extracellular vesicles for management of hepatocellular carcinoma

Biomarkers	Functions	Ref.	Notes
CTCs	Recurrence prediction	Chen et al[47], Wang et al[48] and Zhou et al[49]	A close relationship between postoperative CTC levels and early recurrence in HCC patients after liver transplantation or partial hepatectomy was revealed
	Recurrence prediction	Qi et al[50]	A preoperative CTC count ≥ 16 and a mesenchymal-CTC percentage ≥ 2% were significant risk factors associated with early HCC recurrence, multi-intrahepatic recurrence, and lung metastasis
	Prognostic evaluation	Shen et al[51]	An EpCAM-positive CTC count detected before therapy could predict poor survival of patients with HCC
	Prognostic evaluation	Hamaoka et al[52]	A GPC3-positive CTC count detected before therapy could predict poor survival of patients with HCC
	Prognostic evaluation	Luo et al[53]	The presence of CTC-associated white blood cell clusters detected before therapy could predict poor survival of patients with HCC
	Diagnosis/management	Guo et al[54]	A CTC panel including four putative stem cell biomarkers showed great potential in HCC diagnosis, outcome prediction, as well as treatment response evaluation
	Monitoring response to therapy	Rau et al[55]	Changes in some CTCs could reflect treatment response to regional therapies, particularly helpful in monitoring AFP-negative HCCs
EVs	Therapeutic targets	Son et al[66]	A new strategy of transferring the sodium/iodide symporter protein to cells via EVs was explored to increase iodine uptake and cytotoxicity in the HCC cells
		Pomatto et al[67]	Mild electroporation allowed a more efficient and functional miRNA encapsulation in EVs and achieved better protection of antitumor miRNAs from RNase degradation
		Liu et al[68] and Wang et al[69]	Hepatic stellate cell-derived EVs loaded with therapeutic nucleic acids such as miR-30a-3p and miR-335-5p decelerated the progress of HCC by directly regulating targets
		Lu et al[72]	AFP-enriched exosomes derived from dendritic cells allowed the stimulation of antitumor immune responses in autochthonous HCC mouse models in eliciting tumor regression

AFP: Alpha-fetoprotein; HCC: Hepatocellular carcinoma; CTC: Circulating tumor cell; EpCAM: Epithelial cell adhesion molecule; GPC3: Glypican-3; HBV: Hepatitis B virus; EV: Extracellular vesicles.