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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