Liquid biopsy in hepatocellular carcinoma: circulating tumor cells and circulating tumor DNA

Ye, Qianwei; Ling, Sunbin; Zheng, Shusen; Xu, Xiao

doi:10.1186/s12943-019-1043-x

Molecular Cancer

Table 2 Different targets of ctDNA in HCC

From: Liquid biopsy in hepatocellular carcinoma: circulating tumor cells and circulating tumor DNA

Region	HCC patients	Background liver status	ctDNA abnormalities methodology	Target	Ref.
United States	14	HBV^a: 7.1%	Single nucleotide mutation	TP53, CTNNB1, PTEN, CDKN2A, ARID1A, MET	Ikeda et al [54], 2018
		HCV^b: 50%
		Alcohol: 14%
		Alcohol: 14%	Amplification NGS^c	CDK6, EGFR, MYC, BRAF, RAF1, FGFR1, CCNE1, PIK3CA
Taiwan	237	HBV: 57.4% HCV: 29.5%	Methylation Pyrosequencing, Real-time PCR^d	TBX2	Wu et al [55], 2017
Taiwan	180	HBV: 43% HCV: 15%	Methylation MS-PCR^e	APC, COX2, RASSF1A	Lu et al [56], 2017
China	41	Alcohol: 34% LC^f: 59% HBV: 92.7%	Single nucleotide mutation MiSeq™ system	TP53, CTNNB1, TERT	Liao et al [57], 2016
China	48	HBV: 81% LC: 83%	Single nucleotide mutation ddPCR^g	TP53, CTNNB1, TERT	Huang et al [58], 2016
Taiwan	40	Not applicable	Methylation MS-PCR	HOXA9	Kuo et al [59], 2014
China	121	HBV: 83%	Methylation MS-PCR	MT1M	Ji et al [60], 2014
United States	66	HCV: 100% HCV and HBV: 6%	Methylation Pyrosequencing, MS-PCR	INK4A	Huang et al [61], 2014
China	160	HBV: 22%	Methylation MS-PCR	TRG5	Han et al [62], 2014
China	37	HBV: 100%	Methylation Bead Chip, Hot-start PCR, Pyrosequencing	DBX2, THY1	Zhang et al [63], 2013
China	43	HBV: 86%	Methylation MS-PCR	TFPI2	Sun et al [64], 2013
Italy	66	HCV: 51% Alcohol: 27%	Quantitative analysis Real-time PCR	hTERT	Piciocchi et al [65], 2013
Egypt	40	HCV: 100%	Methylation Real-time PCR	RASSF1A	Mohamed et al [66], 2012
Japan	220	HCV: 100%	Methylation MS-PCR	SPINT2, SRD5A2	Iizuka et al [67], 2011
China	72	HBV: 85%	Methylation MSRE-qPCR^h	APC, GSTP1, RASSF1A, SFRP1	Huang et al [68], 2011
China	60	Not applicable	Quantitative analysis FQ-PCRⁱ	hTERT	Yang et al [69], 2011
Egypt	28	HCV: 79% HBV: 18%	Methylation MS-PCR	APC, FHIT, P15, P16 E-cadherin	Iyer et al [70], 2010
China	130	Mostly HBV	Single nucleotide mutation RFLP^j and SOMA^k	R249S (TP53 mutation)	Szymanska et al [71], 2009
China	19	HBV: 89%	Methylation MS-PCR	APC, GSTP1, RASSF1A, P16, E-cadherin	Chang et al [72], 2008
Hong Kong	85	HBV: 92%	Methylation RT-PCR^l	RASSFIA	Chan et al [28], 2008
Taiwan	50	HBV: 22% HCV: 16%	Methylation MS-PCR	P15, P16	Zhang et al [73], 2007
Singapore	8	Not applicable	Methylation MS-PCR	RUNX3	Tan et al [74], 2007
China	79	HBV: 85% LC: 86%	Quantitative analysis Real-time PCR Allelic imbalance analysis	Not applicable D8S258 D8S264	Ren et al [75], 2006
Japan	52	HCV: 100%	Quantitative analysis Real-time PCR	GSTP1	Iizuka et al [76], 2006
Hong Kong	40	HBV: 83%	Methylation MS-PCR	RASSF1A	Yeo et al [77], 2005
Korea	46	HBV: 65% HCV: 22%	Methylation MS-PCR	P16INK4A	Chu et al [78], 2004
Hong Kong	49	Not applicable	Methylation MS-PCR	p16INK4a	Wong et al [79], 2003
Qidong, China	25	HBV: 84%	Single nucleotide mutation Direct sequencing	249^Ser p53 mutation	Huang et al [80], 2003
Hong Kong	25	HBV: 88% HCV: 2%	Methylation MS-PCR	P16	Wong et al [81], 2000

^aHepatitis B Virus
^bHepatitis C Virus
^cNext-Generation Sequencing
^dPolymerase Chain Reaction
^eMethylation-specific PCR
^fLiver cirrhosis
^gDroplet Digital PCR
^hMethylation-sensitive restriction enzymes-based quantitative PCR
ⁱReal-time quantitative fluorescent PCR
^jRestriction fragment length polymorphism
^kShort oligonucleotide mass analysis
^lReverse transcription PCR

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