Liquid biopsy in patients with hepatocellular carcinoma: Circulating tumor cells and cell-free nucleic acids

Table 1 Circulating tumor cells in hepatocellular carcinoma

Ref.	HCC patients	Ethnicity	Background liver status	Patient background	Controls	Methodology	Positive rate
Matsumura, et al[51], 1999	88	Japan	HCV: 85%, HBV: 6%	Pre and post (TAE or PEI)	NA	RT-PCR (AFP)	63.0%
Mou et al[56], 2002	30	China	HBV: 100%	Pre resection	25 (HV: 25)	RT-PCR (MAGE1/3)	43.3%
			LC: 100%
Witzigmann et al[55], 2002	85	Germany	NA	Pre, during, post (Resection: 24, LT: 10, TACE: 13, No treatment: 38)	116 ( OLT: 50, HD: 39, HV: 27)	RT-PCR (AFP)	28.0%
Vona et al[31], 2004	44	France	LC: 89%	Pre/post resection: 22	107 (HV: 38, HD: 69)	ISET	52.2%
				Unresectable: 22
Jeng et al[53], 2004	81	China	HBV: 77%, HCV: 38%	Pre and post resection	50 (HV: 30, HD: 20)	RT-PCR (AFP)	23.4%
			LC: 69%
Cillo et al[52], 2004	50	Italy	HCV: 50%,HBV: 12%	Pre (Resection: 17, LT: 9, PT: 17)	50 (HD: 6, OT: 44)	RT-PCR (AFP)	40.0%
			HCV and HBV: 6%
			Alcohol: 10%	No treatment: 7
			LC: 84%
Kong et al[59], 2009	343	South Korea	HBV: 78%, HCV: 10%	Pre (Resection: 12, TACE: 224, RFA: 44, Chemotherapy: 12, Radiotherapy: 12, No treatment: 39)	NA	RT-PCR (AFP)
			Alcohol: 6%			(hTERT)	59.5%
			LC: 52%				14.0%
Fan et al[69], 2011	82	China	HBV: 80%	Pre and post resection	NA	CellSearchTM	68.3%
Xu et al[70], 2011	85	China	HBV: 84%, HCV: 7%	Pre Resection: 63	71 (HD: 37, HV: 20, OT: 14)	CellSearchTM	81.0%
			HBV and HCV: 5%	Clinical Diagnosis: 22
			nonB, nonC: 4%
Liu et al[67], 2013	60	China	HBV: 93%	Pre resection	NA	Flow cytometry	50.0%
			LC: 93%
Yao et al[57], 2013	123	China	HBV: 72%	NA	276 (HV: 30, HD: 196, OT: 50)	RT-PCR (GPC-3)	70.77%
			LC: 93%
Sun et al[73], 2013	123	China	HBV: 75%	Pre/post resection	NA	CellSearchTM	66.6%
			LC: 76%
Schulze et al[72], 2013	59	Germany	Alcohol: 38%	Pre (resection or systemic therapy)	19 (HD: 19)	CellSearchTM	30.5%
			HBV: 17%, HCV: 13%
			LC: 89%
Li et al[71], 2013	60	China	HBV: 92%, HCV: 3%	NA	30 (HD: 10, HV: 10, OT: 10)	CellSearchTM	76.6%
			nonB, nonC: 7%
			LC: 88.7%
Bahnassy et al[68], 2014	70	Egypt	HCV: 100%	NA	63 (HD: 30, HV: 33)	Flow cytometry (CK19, CD90, 133)	73.0%, 49.8%, 69.5%
						RT-PCR (Telomerase, MAGE1/3)	55.7%, 60.0%, 62.9%
Li et al[76], 2014	27	China	NA	NA	61 (HD: 34, HV: 15, OT: 12)	CellSearchTM	88.9%
Mu et al[78], 2014	62	China	HBV: 95.2%	NA	22 (HD: 7, HV: 15)	CellSearchTM	48.3%
Fang et al[74], 2014	42	China	LC: 55%	Pre and post TACE	20 (HV: 10, HD: 10)	CellSearchTM	52.3%
Morris et al[77], 2014	52	United Kingdom	Alcohol: 38%,	No treatment	NA	CellSearchTM	28%
			HBV: 8%			ISET	100%
			Diabetes: 12%
Guo et al[75], 2014	299	China	HBV: 90%	Pre/post (Resection: 157, TACE: 76, RFA: 66)	120 (HV: 71, HD: 25, BT: 24)	CellSearchTM	42.6%
			LC: 90%
Choi et al[58], 2015	81	South Korea	HBV: 80%, HCV: 11%	Pre and post (Resection: 64, LT: 17)	16 (LHD: 16)	RT-PCR (K19, CD44)	22.2%
			Alcohol: 4%
			LC: 59%
Kelley et al[19], 2015	20	Caucasian: 55%,	HBV: 25%, HCV: 45%	NA	10 (HD: 10)	CellSearchTM	40.0%
		Asian: 35%,	HBV and HCV: 10%
		American: 10%	Alcohol: 5%
		(African-5%)	NAFLD: 10%
		(Native-5%)
Wang et al[79], 2016	42	China	HBV: 81%, HCV: 2%	NA	NA	CTC-Chip	59.5%
			nonB, nonC: 17%
Zhang et al[207], 2016	36	China	NA	NA	NA	CTC-Chip	100%

NA: Not applicable; LC: Liver cirrhosis; NAFLD: Non-alcoholic fatty liver disease; TAE: Trans-arterial embolization; PEI: Percutaneous ethanol injection; LT: Liver transplantation; TACE: Trans-catheter arterial chemoembolization; RFA: Radiofrequency ablation; PT: Percutaneous treatment; HV: Healthy volunteers; HD: Hepatic disease without evidence of HCC; OLT: Other malignant liver tumors; BT: Benign tumor; OT: Other cancerous disease; LHD: Liver healthy donors; RT-PCR: Reverse transcriptase polymerase chain reaction; ISET: Isolation by size of epithelial tumor cells.