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

doi:10.3748/wjg.v23.i31.5650

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World J Gastroenterol. Aug 21, 2017; 23(31): 5650-5668
Published online Aug 21, 2017. doi: 10.3748/wjg.v23.i31.5650

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%
Mou et al[56], 2002	30	China	LC: 100%	Pre resection	25 (HV: 25)	RT-PCR (MAGE1/3)	43.3%
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%
Vona et al[31], 2004	44	France	LC: 89%	Unresectable: 22	107 (HV: 38, HD: 69)	ISET	52.2%
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%
Jeng et al[53], 2004	81	China	LC: 69%	Pre and post resection	50 (HV: 30, HD: 20)	RT-PCR (AFP)	23.4%
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%	Pre (Resection: 17, LT: 9, PT: 17)
			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%			(hTERT)	14.0%
Fan et al[69], 2011	82	China	HBV: 80%	Pre and post resection	NA	CellSearch^TM	68.3%
Xu et al[70], 2011	85	China	HBV: 84%, HCV: 7%	Pre Resection: 63	71 (HD: 37, HV: 20, OT: 14)	CellSearch^TM	81.0%
			HBV and HCV: 5%	Clinical Diagnosis: 22
			nonB, nonC: 4%	Clinical Diagnosis: 22
Liu et al[67], 2013	60	China	HBV: 93%	Pre resection	NA	Flow cytometry	50.0%
Liu et al[67], 2013	60	China	LC: 93%	Pre resection	NA	Flow cytometry	50.0%
Yao et al[57], 2013	123	China	HBV: 72%	NA	276 (HV: 30, HD: 196, OT: 50)	RT-PCR (GPC-3)	70.77%
Yao et al[57], 2013	123	China	LC: 93%	NA	276 (HV: 30, HD: 196, OT: 50)	RT-PCR (GPC-3)	70.77%
Sun et al[73], 2013	123	China	HBV: 75%	Pre/post resection	NA	CellSearch^TM	66.6%
Sun et al[73], 2013	123	China	LC: 76%	Pre/post resection	NA	CellSearch^TM	66.6%
Schulze et al[72], 2013	59	Germany	Alcohol: 38%	Pre (resection or systemic therapy)	19 (HD: 19)	CellSearch^TM	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)	CellSearch^TM	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%
Bahnassy et al[68], 2014	70	Egypt	HCV: 100%	NA	63 (HD: 30, HV: 33)	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)	CellSearch^TM	88.9%
Mu et al[78], 2014	62	China	HBV: 95.2%	NA	22 (HD: 7, HV: 15)	CellSearch^TM	48.3%
Fang et al[74], 2014	42	China	LC: 55%	Pre and post TACE	20 (HV: 10, HD: 10)	CellSearch^TM	52.3%
Morris et al[77], 2014	52	United Kingdom	Alcohol: 38%,	No treatment	NA	CellSearch^TM	28%
			HBV: 8%			ISET	100%
			Diabetes: 12%			ISET	100%
Guo et al[75], 2014	299	China	HBV: 90%	Pre/post (Resection: 157, TACE: 76, RFA: 66)	120 (HV: 71, HD: 25, BT: 24)	CellSearch^TM	42.6%
Guo et al[75], 2014	299	China	LC: 90%	Pre/post (Resection: 157, TACE: 76, RFA: 66)	120 (HV: 71, HD: 25, BT: 24)	CellSearch^TM	42.6%
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)	CellSearch^TM	40.0%
		Asian: 35%,	HBV and HCV: 10%
		American: 10%	Alcohol: 5%
		(African-5%)	NAFLD: 10%
		(Native-5%)	NAFLD: 10%
Wang et al[79], 2016	42	China	HBV: 81%, HCV: 2%	NA	NA	CTC-Chip	59.5%
Wang et al[79], 2016	42	China	nonB, nonC: 17%	NA	NA	CTC-Chip	59.5%
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.

Table 2 Circulating cell-free DNA in hepatocellular carcinoma

Ref	HCC patients	Sample	Ethnicity	Background liver	Controls	cfDNA abnormalities	Target
Ref	HCC patients	Sample	Ethnicity	Background liver	Controls	Methodolgy	Target
Wong et al[105], 2000	25	Plasma/serum	Hong-Kong	HBV: 88%	55 (HD: 35, HV: 20)	Methylation	P16
Wong et al[105], 2000	15	Buffy coat	Hong-Kong	HCV: 2%	35 (HD: 15, HV: 20)	MS-PCR	P16
Wong et al[108], 2003	29/22	Plasma/serum	Hong Kong	NA	50 (HD and HV)	Methylation	P16INK4A
Wong et al[108], 2003	29	Buffy coat	Hong Kong	NA	35 (HD: 15, HV: 20)	MS-PCR	P16INK4A
Chu et al[109], 2004	46	Serum	Korea	HBV: 65%	23 (HD: 23)	Methylation	P16INK4A
Chu et al[109], 2004	46	Serum	Korea	HCV: 22%	23 (HD: 23)	MS-PCR	P16INK4A
Yeo et al[110], 2005	40	Plasma	Hong-Kong	HBV: 83%	10 (HV: 10)	Methylation	RASSF1A
Yeo et al[110], 2005	40	Plasma	Hong-Kong	HBV: 83%	10 (HV: 10)	MS-PCR	RASSF1A
Iizuka et al[96], 2006	52	Serum	Japan	HCV: 100%	46 (HD: 30, HV: 16)	Quantitative analysis	GSTP1
Iizuka et al[96], 2006	52	Serum	Japan	HCV: 100%	46 (HD: 30, HV: 16)	Real-time PCR	GSTP1
Ren et al[97], 2006	79	Plasma	China	HBV: 85% LC: 86%	40 (HD: 20, HV: 20)	Quantitative analysis	NA
						Real-time PCR
						Allelic imbalance analysis	D8S258 and D8S264
Zhang et al[112], 2007	50	Serum	Taiwan	HBV: 22%	50	Methylation	P15, P16
Zhang et al[112], 2007	50	Serum	Taiwan	HCV: 16%	HV: 50	MS-PCR	P15, P16
Tan et al[111], 2007	8	Serum	Singapore	NA	72 (OT: 62, HV: 10)	Methylation	RUNX3
Tan et al[111], 2007	8	Serum	Singapore	NA	72 (OT: 62, HV: 10)	MS-PCR	RUNX3
Chan et al[113], 2008	85	Serum	Hong-Kong	HBV: 92%	135 (HD: 63, HV: 72)	Methylation	RASSFIA
Chan et al[113], 2008	85	Serum	Hong-Kong	HBV: 92%	135 (HD: 63, HV: 72)	RT-PCR	RASSFIA
Chang et al[114], 2008	19	Plasma	China	HBV: 89%	17 (LC: 17)	Methylation	APC, GSTP1, RASSF1A, P16, E-cadherin
Chang et al[114], 2008	19	Plasma	China	HBV: 89%	17 (LC: 17)	MS-PCR	APC, GSTP1, RASSF1A, P16, E-cadherin
Iyer et al[115], 2010	28	Plasma	Egypt	HCV: 79%	NA	Methylation	APC, FHIT, P15, P16 and E-cadherin
Iyer et al[115], 2010	28	Plasma	Egypt	HNV: 18%	NA	MS-PCR	APC, FHIT, P15, P16 and E-cadherin
Yang et al[98], 2011	60	Plasma	China	NA	50 (HD: 21, HV: 29)	Quantitative analysis	hTERT
Yang et al[98], 2011	60	Plasma	China	NA	50 (HD: 21, HV: 29)	FQ-PCR	hTERT
Szymañska et al[103], 2011	14	Plasma	China	Mostly HBV	NA	Single nucleotide mutation	R249S (TP53 mutation)
Szymañska et al[103], 2011	14	Plasma	China	Mostly HBV	NA	SOMA	R249S (TP53 mutation)
Iizuka et al[117], 2011	220	Serum	Japan	HCV: 100%	202 (HD: 202)	Methylation	SPINT2, SRD5A2
Iizuka et al[117], 2011	220	Serum	Japan	HCV: 100%	202 (HD: 202)	MS-PCR	SPINT2, SRD5A2
Huang et al[116], 2011	72	Plasma	China	HBV: 85%	37 (HD: 37)	Methylation	APC, GSTP1, RASSF1A, and SFRP1
Huang et al[116], 2011	72	Plasma	China	HBV: 85%	37 (HD: 37)	MSRE-qPCR	APC, GSTP1, RASSF1A, and SFRP1
Huang et al[100], 2012	72	Plasma	China	HBV: 85%	115 (HD: 74, HV: 41)	Quantitative analysis	NA
Huang et al[100], 2012	72	Plasma	China	HBV: 85%	115 (HD: 74, HV: 41)	Real-time PCR	NA
Chen et al[99], 2012	80	Serum	China	HBV: 100%	130 (HD: 80, HV: 50)	Quantitative analysis	NA
Chen et al[99], 2012	80	Serum	China	HBV: 100%	130 (HD: 80, HV: 50)	Real-time PCR	NA
Mohamed et al[118], 2012	40	Serum	Egypt	HCV: 100%	60 (HD: 40, HV: 20)	Methylation	RASSF1A
Mohamed et al[118], 2012	40	Serum	Egypt	HCV: 100%	60 (HD: 40, HV: 20)	Real-time PCR	RASSF1A
Chen et al[101], 2013	39	Serum	China	HBV: 79%	45 (HV: 45)	Quantitative analysis	NA
Chen et al[101], 2013	39	Serum	China	HBV: 79%	45 (HV: 45)	Real-time PCR	NA
Piciocchi et al[102], 2013	66	Plasma	Italy	HCV: 51%	76 (HD: 76)	Quantitative analysis	hTERT
Piciocchi et al[102], 2013	66	Plasma	Italy	Alcohol: 27%	76 (HD: 76)	Real-time PCR	hTERT
Chan et al[95], 2013	4	Plasma	China	NA	20 (HD: 4, HV: 16)	Copy number variation	NA
Chan et al[95], 2013	4	Plasma	China	NA	20 (HD: 4, HV: 16)	MPS	NA
Sun et al[119], 2013	43	Serum	China	HBV: 86%	50 (HD: 24, HV: 26)	Methylation	TFPI2
Sun et al[119], 2013	43	Serum	China	HBV: 86%	50 (HD: 24, HV: 26)	MS-PCR	TFPI2
Zhang et al[120], 2013	37	Serum	China	HBV: 100%	33 (HD: 33)	Methylation	DBX2, THY1
Zhang et al[120], 2013	37	Serum	China	HBV: 100%	33 (HD: 33)	Bead Chip, Hot-start PCR, Pyrosequencing	DBX2, THY1
Huang et al[122], 2014	66	Serum	United States	HCV: 100%	43 (HD: 43)	Methylation	INK4A
Huang et al[122], 2014	66	Serum	United States	HCV and HBV: 6%		Pyrosequencing, MS-PCR
Han et al[121], 2014	160	Serum	China	HBV: 22%	133 (HD: 88, HV: 45)	Methylation	TRG5
Han et al[121], 2014	160	Serum	China	HBV: 22%	133 (HD: 88, HV: 45)	MS-PCR	TRG5
Ji et al[123], 2014	121	Serum	China	HBV: 83%	68 (HD: 37, HV: 31)	Methylation	MT1M
Ji et al[123], 2014	121	Serum	China	HBV: 83%	68 (HD: 37, HV: 31)	MS-PCR	MT1M
Kuo et al[124], 2014	40	Plasma	Taiwan	NA	34	Methylation	HOXA9
Kuo et al[124], 2014	40	Plasma	Taiwan	NA	34	MS-PCR	HOXA9
Jiang et al[104], 2015	90	Plasma	Hong-Kong	NA	135 (HD: 103, HV: 32)	Copy number variation	NA
Jiang et al[104], 2015	90	Plasma	Hong-Kong	NA	135 (HD: 103, HV: 32)	CAZA	NA

NA: Not applicable; HD: Hepatic disease without evidence of HCC; HV: Healthy volunteers; RT-PCR: Reverse transcriptase polymerase chain reaction; SOMA: Short oligonucleotide mass analysis; CAZA: Chromosome arm-level z-score analysis; MPS: Massively parallel sequencing; MS-PCR: Methylation-specific PCR; RT-PCR: Real time polymerase chain reaction; MSRE-qPCR: Methylation-sensitive restriction enzymes-based quantitative PCR; FQ-PCR: Real-time quantitative fluorescent polymerase chain reaction.

Table 3 Circulating cell-free microRNA in hepatocellular carcinoma

miR	Expression	Sample	HCC patients	Ethnicity	Background liver	Controls	Value	Ref.
miR-1	Up	Serum	195	Germany	HCV: 45%, Alcohol: 33%, HBV: 17%	54 (HD: 54)	P	Köberle et al[155] 2013
miR-10b	Up	Blood	27	China	Alcohol: 23%	81 (HD: 81)	D	Jiang et al[175] 2015
miR-15b	Up	Serum	153	China	HBV: 88%	59 (HD: 29, HV: 39)	D	Liu et al[152] 2012
miR-15b-5p	Down	Plasma	37	China	NA	60 (HD: 29, HV: 31)	D	Chen et al[170] 2015
miR-16	Down	Serum	105	United States	HCV: 64%, HBV: 20%	178 (HD: 107, HV: 7)	D	Qu et al[148] 2011
			90	China	NA	60 (HV: 60)	D	Ge et al[161] 2014
			40	Egypt	HCV: 100%	60 (HD: 40, HV: 20)	D	El-Abd et al[174] 2015
miR-17-5p	Up	Serum	136	China	NA	NA	P	Zheng et al[159] 2013
miR-17-5p	Up	Serum	8	Turkey	HCV: 100%	84 (HD: 56, HV: 28)	D	Oksuz et al[178] 2015
miR-18a	Up	Serum	101	China	HBV: 100%	90 (HD: 30, HV: 60)	D	Li et al[151] 2012
miR-18a	Up	Serum	20	South Korea	HBV: 70%	40 (HD: 40)	D	Sohn et al[179] 2015
miR-19a	Down	Serum	112	Egypt	HCV: 100%	167 (HD: 125, HV: 42)	D	Motawi et al[177] 2015
miR-21	Up	Plasma	457	China	HBV:100%	477 (HD: 310, HV: 167)	D	Zhou et al[150] 2011
miR-21		Plasma	136	Japan	HCV:68%, HBV: 23%	80 (HD: 30, HV: 50)	D, P	Tomimaru et al[153] 2012
		Serum	101	China	HBV: 75%	137 (HD: 48, HV: 89)	D	Xu et al[149] 2011
			136	China	HBV: 95%	NA	P	Liu et al[164] 2014
			97	China	HBV: 62%	30 (HV: 30)	D, P	Wang et al[180] 2015
			23	Egypt	HCV: 87%, HBV: 13%	17 (HD: 17)	D	Amr et al[186] 2016
	Down	Serum	70	China	HBV: 100%	72 (HD 48, HV: 24)	D	Qi et al[147] 2011
			90	China	NA	60 (HV: 60)	D, P	Ge et al[161] 2014
			52	China	HBV: 63%, HCV: 4%	85 (HD: 42, HV: 43)	D	Zhuang et al[195] 2016
miR-22	Down	Serum	192	Egypt	HCV: 100%	192 (HD: 192)	D	Zekri et al[194] 2016
miR-24-3p	Up	Serum	84	China	HBV: 100%	77 (HD: 31, HV: 46)	D, P	Meng et al[165] 2014
miR-26a	Down	Plasma	457	China	HBV: 100%	477 (HD: 310, HV: 167)	D	Zhou et al[150] 2011
miR-26a	Down	Serum	52	China	HBV: 63%, HCV: 4%	85 (HD42, HV: 43)	D	Zhuang et al[195] 2016
miR-26a-5p	Down	Serum	261	China	HBV: 100%	406 (HD 233, HV: 173)	D	Tan et al[166] 2014
miR-27a	Down	Plasma	457	China	HBV: 100%	477 (HD: 310, HV: 167)	D	Zhou et al[150] 2011
miR-29b	Down	Serum	192	Egypt	HCV: 100%	192 (HD: 192)	D	Zekri et al[194] 2016
miR-30c	Down	Serum	242	China	HCV: 63%	NA	P	Liu et al[176] 2015
miR-30c-5p	Down	Serum	8	Turkey	HCV: 100%	84 (HD: 56, HV: 28)	D	Oksuz et al[178] 2015
miR-34a	Up	Serum	112	Egypt	HCV: 100%	167 (HD: 125, HV: 42)	D	Motawi et al[177] 2015
miR-92a-3p	Up	Plasma	20	Turkey	HBV: 100%	74 (HD: 46, HV: 28)	D	Giray et al[162] 2014
miR-96	Up	Serum	104	China	HBV: 100%	400 (HD: 280, HV: 120)	D	Chen et al[171] 2015
miR-101	Up	Serum	25	China	HBV: 100%	20 (HV: 20)	D	Fu et al[154] 2013
	Down	Serum	67	China	HBV: 100%	170 (HD: 140, HV: 3,)	D	Xie et al[167] 2014
			20	South Korea	HBV: 70%	40 (HD: 40)	D	Sohn et al[179] 2015
			52	China	HBV: 63%, HCV: 4%	85 (HD: 42, HV: 43)	D	Zhuang et al[195] 2016
miR-106b	Up	Blood	27	China	Alcohol: 23%	81 (HD: 31, HV: 50,)	D	Jiang et al[175] 2015
miR-122	Up	Serum	70	China	HBV: 100%	72 (HD: 48, HV: 24,)	D	Qi et al[147] 2011
			101	China	HBV: 75%	137 (HD: 48, HV: 89,)	D	Xu et al[149] 2011
			195	Germany	HCV: 45%, Alcohol: 33%, HBV: 17%	54 (HD: 54)	P	Köberle et al[155] 2013
			30	Egypt	HCV: 100%	70 (HD: 60, HV: 10)	D	El-Garem et al[160] 2014
			136	China	HBV: 95%	NA	P	Liu et al[164] 2014
			192	Egypt	HCV: 100%	192 (HD: 192)	D	Zekri et al[194] 2016
	Down	Plasma	457	China	HBV: 100%	477 (HD: 310, HV: 167)	D	Zhou et al[150] 2011
		Serum	20	South Korea	HBV: 70%	40 (HD: 40)	D	Sohn et al[179] 2015
		Serum	122	China	NA	NA	P	Xu et al[181] 2015
miR-122a	Down	Serum	85	China	HBV: 88%	HV (HV: 85)	D	Luo et al[156] 2013
miR-122-5p	Up	Plasma	20	Turkey	HBV: 100%	74 (HD: 46, HV: 28)	D	Giray et al[162] 2014
		Plasma	120	South Korea	HBV: 100%	NA	P	Cho et al[172] 2015
		Serum	120	China	HBV: 100%	DN: 30	D	Hung et al[189] 2016
	Down	Serum	261	China	HBV: 100%	406 (HD: 233, HV: 173)	D	Tan et al[166] 2014
miR-125b	Down	Plasma	64	China	HBV: 100%	178 (HD: 122, HV: 56)	D	Chen et al[187] 2016
miR-125b-5p	Up	Plasma	20	Turkey	HBV: 100%	74 (HD: 46, HV: 28)	D	Giray et al[162] 2014
miR-126	Up	Plasma	59	India	HBV: 100%	38 (HD: 20, HV: 18)	D	Ghosh et al[188] 2016
miR-126	Down	Serum	23	Egypt	HCV: 100%	55 (HD: 55)	D	Khairy et al[190] 2016
miR-128-2	Up	Serum	222	China	HBV: 87%	NA	P	Zhuang et al[184] 2015
miR-129	Down	Serum	23	Egypt	HCV: 100%	55 (HD: 55)	D	Khairy et al[190] 2016
miR-130a	Up	Serum	112	Egypt	HCV: 100%	167 (HD: 125, HV: 42)	D	Motawi et al[177] 2015
miR-130b	Up	Serum	153	China	HBV: 88%	59 (HD: 29, HV: 30)	D	Liu et al[152] 2012
miR-139	Down	Plasma	31	China	NA	31 (HD: 31)	D, P	Li et al[163] 2014
miR-141-3p	Up	Serum	261	China	HBV: 100%	406 (HD: 233, HV: 173)	D	Tan et al[166] 2014
miR-143	Up	Serum	95	China	NA	245 (HD: 118, HV: 127)	D	Zhang et al[168] 2014
miR-143-3p	Up	Plasma	59	India	HBV: 100%	38 (HD: 20, HV: 18)	D	Ghosh et al[188] 2016
miR-146a	Up	Serum	112	Egypt	HCV: 100%	167 (HD: 125, HV: 42)	D	Motawi et al[177] 2015
miR-150	Down	Serum	120	China	HBV: 100%	230 (HD: 110, HV: 120)	D, P	Yu et al[183] 2015
miR-155	Down	Serum	23	Egypt	HCV: 100%	55 (HD: 55)	D	Khairy et al[190] 2016
miR-181a	Down	Blood	27	China	Alcohol: 23%	81 (HD: 31, HV: 50)	D	Jiang et al[75] 2015
miR-181b	Up	Serum	192	Egypt	HCV: 100%	192 (HD: 192)	D	Zekr et al[194] 2016
miR-182	Up	Serum	103	China	NA	135 (HD: 95, HV: 40)	D, P	Chen et al[169] 2015
miR-192	Up	Plasma	457	China	HBV: 100%	477 (HD: 310, HV: 167)	D	Zhou et al[150] 2011
miR-192	Up	Serum	112	Egypt	HCV: 100%	167 (HD: 125, HV: 42)	D	Motawi et al[177] 2015
miR-192-5p	Down	Serum	261	China	HBV: 100%	406 (HD: 233, HV: 173)	D	Tan et al[166] 2014
miR-195	Down	Serum	112	Egypt	HCV: 100%	167 (HD: 125, HV: 42)	D	Motawi et al[177] 2015
miR-195	Down	Serum	20	South Korea	HBV: 70%	40 (HD: 40)	D	Sohn et al[179] 2015
miR-199a	Down	Serum	105	United States	HCV: 64%, HBV: 20%	178 (HD: 107, HV: 71)	D	Qu et al[148] 2011
			40	Egypt	HCV: 100%	60 (HD: 40, HV: 20)	D, P	El-Abd et al[174] 2015
			78	China	NA	156 (HV: 156)	D	Yin et al[182] 2015
			23	Egypt	HCV: 87%, HBV: 13%	17 (HD: 17)	D	Amr et al[186] 2016
miR-199a-3p	Down	Serum	192	Egypt	HCV: 100%	192 (HD: 192)	D	Zekri et al[194] 2016
miR-199a-5p	Down	Serum	261	China	HBV: 100%	406 (HD: 233, HV: 173)	D	Tan et al[166] 2014
miR-200a	Up	Serum	136	China	HBV: 95%	NA	P	Liu et al[176] 2015
miR-203	Down	Serum	23	Egypt	HCV: 100%	55 (HD: 55)	D	Khairy et al[190] 2016
miR-203a	Down	Serum	242	China	HCV: 63%	NA	P	Liu et al[176] 2015
miR-206	Up	Serum	261	China	HBV: 100%	406 (HD: 233, HV: 173)	D	Tan et al[166] 2014
miR-215	Up	Serum	95	China	NA	245 (HD: 118, HV: 127)	D	Zhang et al[168] 2014
miR-218	Down	Serum	156	China	HBV: 72%	162 (HD: 98, HV: 64)	D, P	Yang et al[193] 2016
miR-221	Up	Serum	20	South Korea	HBV: 70%	40 (HD: 40)	D	Sohn et al[179] 2015
	Up	Serum	192	Egypt	HCV: 100%	192 (HD: 192)	D	Zekri et al[194] 2016
	Down	Serum	30	Egypt	HCV: 100%	70 (HD: 60, HV: 10)	D	El-Garem et al[174] 2014
miR-222	Up	Serum	70	China	HBV: 100%	72 (HD: 48, HV: 24)	D	Qi et al[147] 2011
miR-222	Up	Serum	20	South Korea	HBV: 70%	40 (HD: 40)	D	Sohn et al[179] 2015
miR-223	Up	Serum	70	China	HBV: 100%	72 (HD: 48, HV: 24)		Qi et al[147] 2011
	Up	Serum	101	China	HBV: 75%	137 (HD: 48, HV: 89)	D	Xu et al[149] 2011
	Down	Plasma	457	China	HBV: 100%	477 (HD: 310, HV: 167)	D	Zhou et al[150] 2011
	Down	Serum	23	Egypt	HCV: 100%	55 (HD: 55)	D	Khairy et al[190] 2016
miR-223-3p	Down	Plasma	20	Turkey	HBV: 100%	74 (HD: 46, HV: 28)	D	Giray et al[162] 2014
miR-223-3p	Down	Serum	8	Turkey	HCV: 100%	84 (HD: 56, HV: 28)	D	Oksuz et al[178] 2015
miR-224	Up	Plasma	107	Japan	HCV: 41%, HBV: 18%, Alcohol: 15%	102 (HD: 27, HV: 75)	D, P, T	Okajima et al[192] 2016
		Serum	20	South Korea	HBV: 70%	40 (HD: 40)	D	Sohn et al[179] 2015
			182	China	HBV: 87%	NA	D, P	Zhuang et al[185] 2015
			122	China	HBV: 100%	157 (HD: 135, HV: 22)	D	Lin et al[191] 2016
miR-224-5p	Up	Serum	136	China	HBV: 95%	NA	P	Liu et al[164] 2014
miR-296	Up	Serum	112	Egypt	HCV: 100%	167 (HD: 125, HV: 42)	D	Motawi et al[177] 2015
miR-302c-3p	Down	Serum	8	Turkey	HCV: 100%	84 (HD: 56, HV: 28,)	D	Oksuz et al[178] 2015
miR-331-3p	Up	Serum	103	China	NA	135 (HD: 95, HV: 40)	D, P	Chen et al[169] 2015
miR-335	Down	Serum	125	China	NA	250 (HD: 125, HV: 125)	D, P	Cui et al[173] 2015
miR-338-5p	Up	Plasma	37	China	NA	60 (HD: 29, HV: 31)	D	Chen et al[170] 2015
miR-375	Up	Serum	120	China	HBV: 100%	393 (HD: 183, HV: 210)	D	Li et al[145] 2010,
miR-375	Down	Serum	78	China	NA	156 (HV: 156)	D	Yin et al[182] 2015.
miR-433-3p	Up	Serum	261	China	HBV: 100%	406 (HD: 233, HV: 173)	D	Tan et al[166] 2014
miR-483-5p	Up	Serum	69	United States	HCV: 63%, HBV: 14%	69 (HV: 69)	D	Shen et al[157] 2013
miR-483-5p	Up	Serum	112	China	NA	141 (HD: 56, HV: 85)	D	Zhang et al[158] 2013
miR-500a	Up	Serum	112	China	NA	141 (HD: 56, HV: 85)	D	Zhang et al[158] 2013
miR-764	Up	Plasma	37	China	NA	60 (HD: 29, HV: 31)	D	Chen et al[170] 2015
miR-801	Up	Plasma	457	China	HBV: 100%	477 (HD: 310, HV: 167)	D	Zhou et al[150] 2011
miR-885-5p	Up	Serum	46	China	HBV: 72%	105 (HD: 64, HV: 24, GC: 17)	D	Gui et al[146] 2011
miR-885-5p	Up	Serum	192	Egypt	HCV: 100%	192 (HD: 192)	D	Zekri et al[194] 2016
miR-1228-5p	Up	Serum	261	China	HBV: 100%	406 (HD: 233, HV: 173)	D	Tan et al[166] 2014
let-7b	Up	Serum	120	China	HBV: 100%	30 (DN: 30)	D	Hung et al[189] 2016
let-7f	Down	Serum	90	China	NA	60 (HV: 60)	D, P	Ge et al[161] 2014

NA: Not applicable; HV: Healthy volunteers; HD: Hepatic disease without evidence of HCC; GC: Gastric cancer; DN: Dysplastic nodule; D: Diagnostic marker; P: Prognostic marker; T: Treatment outcome marker.

Citation: Okajima W, Komatsu S, Ichikawa D, Miyamae M, Ohashi T, Imamura T, Kiuchi J, Nishibeppu K, Arita T, Konishi H, Shiozaki A, Morimura R, Ikoma H, Okamoto K, Otsuji E. Liquid biopsy in patients with hepatocellular carcinoma: Circulating tumor cells and cell-free nucleic acids. World J Gastroenterol 2017; 23(31): 5650-5668
URL: https://www.wjgnet.com/1007-9327/full/v23/i31/5650.htm
DOI: https://dx.doi.org/10.3748/wjg.v23.i31.5650