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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 HBVa: 7.1% Single nucleotide mutation TP53, CTNNB1, PTEN, CDKN2A, ARID1A, MET Ikeda et al [54], 2018
HCVb: 50%
Alcohol: 14%
Amplification NGSc CDK6, EGFR, MYC, BRAF, RAF1, FGFR1, CCNE1, PIK3CA  
Taiwan 237 HBV: 57.4%
HCV: 29.5%
Methylation
Pyrosequencing,
Real-time PCRd
TBX2 Wu et al [55], 2017
Taiwan 180 HBV: 43%
HCV: 15%
Methylation
MS-PCRe
APC, COX2, RASSF1A Lu et al [56], 2017
China 41 Alcohol: 34%
LCf: 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
ddPCRg
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-qPCRh
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
RFLPj and SOMAk
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-PCRl
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
249Ser p53 mutation Huang et al [80], 2003
Hong Kong 25 HBV: 88%
HCV: 2%
Methylation
MS-PCR
P16 Wong et al [81], 2000
  1. aHepatitis B Virus
  2. bHepatitis C Virus
  3. cNext-Generation Sequencing
  4. dPolymerase Chain Reaction
  5. eMethylation-specific PCR
  6. fLiver cirrhosis
  7. gDroplet Digital PCR
  8. hMethylation-sensitive restriction enzymes-based quantitative PCR
  9. iReal-time quantitative fluorescent PCR
  10. jRestriction fragment length polymorphism
  11. kShort oligonucleotide mass analysis
  12. lReverse transcription PCR