Background
References | Origin | HCC (n) | Technique | Circulating markers | ctDNA mutation (%) | tiDNA mutation (%) | Mutation in liquid and tumor tissue | Carcinoma vs. healthy | Biomarker | ||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Sensitivity (%) | Specificity (%) | Concordance ctDNA/tiDNA (%) | Sensitivity (%) | Specificity (%) | |||||||||
Huang et al. (2016) | Plasma | 48 | ddPCR Sanger seq | TERT CTNNB1 TP53 | 24.4 12.2 14.6 | 19.5 0 4.9 | 62.5 NA 50.0 | 84.9 87.8 87.2 | 80.5 87.8 85.4 | NA | NA | NA | |
Liao et al. (2016) | Plasma | 41 | NGS | TERT CTNNB1 TP53 | 4.9 9.8 4.9 | 70.7 26.8 65.9 | 6.9 27.3 2.3 | 95.1 96.7 100.0 | 34.1 78.0 39.0 | NA | NA | Poor RFS | |
An et al. (2019) | Plasma | 26 | NGS | 354 genes (TP53) | 96.2 50 | NA 30.8 | NA | NA | 88.5 69.2 | NA | NA | DFS (HR = 7.66; p < 0.001) | |
Szymanska et al. (2004) | Plasma | 17 | PCR–RFLP SOMA | TP53 | 41 | 34.5 | 71.4 | 61.5 | 76.7 | NA | NA | NA | |
Lin et al. (2011) | Urine | 17 | LNA PCR | TP53 | 52.9 | 42.9 | 66.7 | 0.0 | 28.6 | 53.0 | 75.0 | NA | |
Kimbi et al. (2005) | Serum | 158 | PCR and Seq | TP53 | 17.7 | NA | NA | NA | NA | 18 | 83.3 | NA | |
Marchio et al. (2018) | Plasma | 149 | ddPCR | TP53 | 24.8 | NA | NA | NA | NA | NA | NA | NA | |
Ikeda et al. (2018b) | Plasma | 14 | NGS | 68 genes (TP53) | 79 57 | NA | NA | NA | NA | NA | NA | NA | |
Ikeda et al. (2018a) | Blood | 26 | NGS | 70 genes (TP53) | 88.5 61.5 | NA | NA | NA | NA | NA | NA | NA | |
Riviere et al. (2018) | Plasma | 31 | NGS | 68 genes (TP53) | 74 61.2 | NA | NA | NA | NA | NA | NA | NA | |
He et al. (2019) | Plasma | 29 | NGS | 35 genes (TP53) | 96.4 50 | NA | 75 NA | NA | 75 33 | NA | NA | NA | |
Kaseb et al. (2019) | Plasma | 219 | NGS | 70 genes | 87.8 | NA | NA | NA | NA | NA | NA | NA | |
Xiong et al. (2019) | Plasma | 37 | NGS | TP53 | 64 | NA | NA | NA | NA | 65 | 100 | NA | |
Xu et al. (2017) | Plasma | 1098 | MSP | target panel | NA | NA | NA | NA | NA | 85.7 | 94.3 | OS (HR = 2.41; p < 0.001) | |
Iyer et al. (2010) | Plasma | 28 | MSP | mp15 mp16 mAPC mFHIT | 10.7 46.4 53.5 67.8 | 14.2 71.4 64.2 75 | 50 60 77.8 94.7 | 95.8 87.5 90 66.7 | 89.2 67.9 82.1 85.7 | NA | NA | NA | |
Wong et al. (1999) | Plasma | 22 | MSP | mp16 | 59.1 | 72.7 | NA | NA | 81 | NA | NA | NA | |
Wong et al. (2000) | Plasma | 25 | MSP | mp15 / mp16 | 87 | 92 | NA | NA | 74 | NA | NA | NA | |
Wong et al. (2003) | Plasma | 29 | MSP | mp16INK4a | 79.3 | 66.7 | NA | NA | 46.7 | NA | NA | NA | |
Huang et al. (2014) | Serum | 66 | MSP | mINK4A | 65.3 | NA | NA | NA | NA | 65.3 | 87.2 | NA | |
Huang et al. (2011) | Plasma | 72 | MSP | mAPC, mGSTP1, mRASSF1A, and mSFRP1 | 84.7 | NA | NA | NA | NA | 92.7 | 81.9 | OS (HR = 3.26; p = 0.003) | |
Chan et al. (2008) | Serum | 63 | MSP | mRASSF1A | 93 | NA | NA | NA | NA | 77 | 89 | poor DFS | |
Yeo et al. (2005) | Plasma | 40 | MSP | mRASSF1A | 42.5 | 92.5 | 45.9 | 100.0 | 50.0 | NA | NA | NA | |
Hu et al. (2010) | Serum | 35 | MSP | mRASSF1A | 40 | 88.6 | 45.2 | 100 | 51.4 | 70–100 | 52–100 | NA | |
Mohamed et al. (2012) | Serum | 40 | MSP | mRASSF1A | 90 | NA | NA | NA | NA | 75 | 80 | NA | |
Serum | 45 | MSP | mRASSF1A | 87.7 | NA | NA | NA | NA | 86.7 | 72.5 | correlation with tumor size (r = 0.728; p < 0.001) | ||
Liu et al. (2017) | Serum | 105 | MSP | mRASSF1A hypomLINE-1 | 73.3 66.7 | NA | NA | NA | NA | NA | NA | poor DFS and OS | |
Tangkijvanich et al. (2007) | Serum | 85 | MSP | hypomLINE-1 | 70.4 | NA | NA | NA | NA | NA | NA | increased HCC risk (OR = 1.74), poor OS | |
Oussalah et al. (2018) | Plasma | 51 | MSP | mSEPT9 | 83.0 | NA | NA | NA | NA | 94.1 | 84.4 | NA | |
Sun et al. (2013) | Serum | 43 | MSP | mTFPI2 | 46.5 | NA | NA | NA | NA | 80.8 | 80 | NA | |
Wu et al. (2017) | Plasma | 237 | MSP | mTBX2 | 75.5 | NA | NA | NA | NA | 75.5 | 41.2 | Increased HCC risk (OR = 2.39) | |
Iizuka et al. (2011) | Serum | 108 | MSP | mBASP1 mCCND2 mAPC mCFTR mRASSF1A | NA | NA | NA | NA | NA | 62.0 64.8 17.6 56.5 83.3 | 78.6 42.9 78.6 83.9 58.9 | NA | |
Zhang et al. (2013) | Serum | 31 | MSP | mDBX2 mTHY1 | NA | NA | NA | NA | NA | 88.9 85.2 | 87.1 80.7 | NA | |
Ji et al. (2014) | Serum | 121 | MSP | mMT1M mMT1G mMT1M/G | 48.8 70.2 | NA | NA | NA | NA | 48.8 70.2 90.9 | 93.5 87.1 83.9 | Correlation with tumor size (r = 0.321; p < 0.001) | |
Han et al. (2014) | Serum | 160 | MSP | mTGR5 mTGR5 and mAFP | 48.1 NA | NA | NA | NA | NA | NA 65.0 | NA 85.2 | NA | |
Wang et al. (2006) | Serum | 32 | MSP | GSTP1 | 50 | 88.5 | 60.9 | 100 | 65.4 | 50.0 | 62.5 | NA | |
Wen et al. (2015) | Plasma | 36 | MSP | mRGS10, mST8SIA6, mVIM, and mRUNX2 | 85.6 | NA | NA | NA | NA | 94.0 | 89.0 | NA |
Reference | Origin | PC (n) | Technique | Circulating markers | ctDNA mutation (%) | tiDNA mutation (%) | Mutation in liquid and tumor tissue | Carcinoma vs. healthy | Biomarker | |||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Sensitivity (%) | Specificity (%) | Concordance ctDNA/tiDNA (%) | Sensitivity (%) | Specificity (%) | ||||||||
Riviere et al. (2018) | Plasma | 25 | NGS | KRAS MYC EGFR | NA | NA | NA | NA | 96 94 91 | NA | NA | NA |
Jiao et al. (2007) | Plasma | 83 | PCR and Seq MSP | KRAS mppENK, mp16 | 62.7 | NA | NA | NA | NA | NA | NA | NA |
Patel et al. (2019) | Blood | 112 | NGS | KRAS TP53 | 43.8 45.8 | 90.9 77.3 | NA | NA | 52 61 | NA | NA | ctDNA: OS (HR = 4.35; p = 0.001) |
Watanabe et al. (2019) | Plasma | 39 | ddPCR | KRAS | 30.8 | 88.1 | NA | NA | NA | NA | NA | OS (HR = 54.5; p < 0.001) |
Takai et al. (2015) | Plasma | 259 | ddPCR | KRAS | 32 | NA | NA | NA | NA | NA | NA | NA |
Sugimori et al. (2020) | Plasma | 45 | ddPCR | KRAS | 51.1 | 95.7 | NA | NA | NA | NA | NA | Worse PFS |
Groot et al. (2019) | Preop plasma | 59 | ddPCR | KRAS | 49 | NA | 90 | 88 | NA | NA | NA | RFS (HR = 2.67; p = 0.011); OS (HR = 2.37; p = 0.048) |
Tjensvoll et al. (2016) | Plasma | 14 | PNA-clamp PCR | KRAS Pre-CTX | 71.4 | NA | NA | NA | NA | NA | NA | RFS (HR = 1.29; p = 0.014); OS (HR = 1.43; p = 0.01) |
Chen et al. (2017) | Plasma | 189 | NGS | KRAS | 93.7 | NA | NA | NA | NA | NA | NA | TTP (HR = 1.45; p = 0.002); OS (HR = 1.45; p = 0.001) |
Kinugasa et al. (2015) | Serum | 66 | ddPCR, PCR-PHFA | KRAS | 62.6 | 74.7 | 76.8 | 78.9 | 77.3 | NA | NA | OS (HR = 3.24; p = 0.001) |
Adamo et al. (2017) | Plasma | 26 | NGS | KRAS | 27 | 78 | NA | NA | NA | NA | NA | OS (HR = 2.89; p = 0.018) |
Maire et al. (2002) | Serum | 47 | PCR | KRAS | 47 | NA | NA | NA | NA | 47 | 87 | NA |
Dianxu et al. (2002) | Plasma | 41 | PCR–RFLP Seq | KRAS | 70.7 | 91.7 | 75.8 | 100.0 | 77.8 | NA | 100 | NA |
Pratt et al. (2019) | Plasma | 17 | ddPCR | KRAS | 86 | NA | 86 | 70 | NA | NA | NA | NA |
Earl et al. (2015) | Plasma | 31 | ddPCR | KRAS | 25.8 | 58.3 | 42.9 | 60 | 50 | NA | NA | OS (HR = 12.2; p < 0.001) |
Uemura et al. (2004) | Plasma | 28 | Mismatch ligation assay | KRAS | 32.1 | 92.9 | 34.6 | 100.0 | 39.2 | NA | 100 | NA |
Marchese et al. (2006) | Plasma | 30 | PCR and Seq | KRAS | 0 | 70 | NA | NA | NA | NA | NA | NA |
Park et al. (2018) | Plasma | 17 | Targeted-NGS and ddPCR | KRAS | 58.8 | 76.5 | NA | NA | NA | NA | NA | NA |
Del Re et al. (2017) | Plasma follow-up during palliative CTX | 27 | ddPCR | KRAS | 70.4 | NA | NA | NA | NA | NA | NA | PFS (2.5 vs. 7.5 months; p = 0.03); OS (6.5 vs. 11.5 months; p = 0.009) |
Perets et al. (2018) | Plasma | 17 | NGS | KRAS | 29.4 | NA | NA | NA | NA | NA | NA | OS (r = -0.76; p = 0.03) |
Kim et al. (2018) | Plasma | 106 | ddPCR | KRAS | 80.5 | 96.1 | 78.4 | 33.3 | NA | NA | NA | PFS (HR = 2.08; p = 0.009) OS (HR = 1.97; p = 0.034) |
Lin et al. (2018) | Plasma | 65 | ddPCR | KRAS | 80 | 100 | NA | NA | 100 | NA | NA | OS (HR = 3.1; p < 0.001) |
Chen et al. (2010) | Plasma | 91 | PCR | KRAS | 33 | NA | NA | NA | NA | NA | NA | ctDNA: OS (HR = 7.39; p < 0.001) |
Cohen et al. (2017) | Plasma | 221 | NGS | KRAS KRAS and four proteins | 30 NA | NA NA | NA NA | NA NA | 100 NA | NA 64 | NA 99.5 | NA |
Nakano et al. (2018) | Serum | 45 | PNA clamp PCR | KRAS | 24.4 (pre-op) 44.4 (post-op) | 83.3 | NA | NA | NA | NA | NA | RFS (HR = 2.92; p = 0.027) |
Kruger et al. (2018) | Plasma | 54 | BEAMing | KRAS | 67 | 58 | 75 | 100 | 79 | 83 | 100 | Early CTX response prediction |
Hadano et al. (2016) | Preop plasma | 105 | ddPCR | KRAS | 31 | 82 | NA | NA | 100 | NA | NA | OS (HR = 3.2; p < 0.001) |
Dabritz et al. (2009) | Plasma | 56 | PNA clamp PCR | KRAS | 36 | 100 | NA | NA | NA | NA | NA | NA |
Wu et al. (2014) | Plasma | 36 | COLD-PCR Sanger sec | KRAS | 72.2 | NA | 80.6 | 87.5 | NA | NA | NA | NA |
Semrad et al. (2015) | Plasma | 27 | PCR | KRAS | 37 | 78 | NA | NA | NA | NA | NA | DFS (1.8 vs. 4.6 months; p = 0.014) OS (3.0 vs. 10.5 months; p = 0.003) |
Sausen et al. (2015) | Plasma | 51 | ddPCR | KRAS | 43 | 88 | NA | 99.9 | NA | NA | NA | NA |
Ako et al. (2017) | Serum, plasma | 40 | ddPCR | KRAS | 48 | 93 | NA | NA | NA | NA | NA | Poor prognosis |
Van Laethem et al. (2017) | Plasma | 60 | BEAMing | KRAS | 65 | NA | NA | NA | NA | NA | NA | PFS (HR = 0.32; p = 0.002) OS (HR = 0.27; p = 0.001) |
Wei et al. (2019) | Plasma | 38 | NGS | KRAS T53 | 84 60 | NA | NA | NA | NA | NA | NA | Correlation with tumor burden post CTX |
Pietrasz et al. (2017) | Plasma | 135 | NGS and ddPCR | KRAS TP53 SMAD4 | 41.3 22.1 7.7 | NA | NA | NA | NA | NA | NA | ctDNA: OS (HR = 1.99; p = 0.016) |
Zill et al. (2015) | Plasma | 17 | NGS | KRAS | 58.8 | 64.7 | 100 | 100 | 100 | NA | NA | NA |
TP53 | 52.9 | 58.8 | 90 | 100 | 94 | |||||||
APC | 11.8 | 11.8 | 100 | 100 | 100 | |||||||
SMAD4 | 5.9 | 11.8 | 100 | 100 | 94 | |||||||
FBXW7 | 11.8 | 5.9 | 50 | 100 | 100 | |||||||
KRAS, TP53, APC, SMAD, and FBXW7 | 82.3 | 88.2 | 92.3 | 100 | 97.7 | |||||||
Pishvaian et al. (2017) | Blood | 23 | NGS | KRAS T53 SMAD4 CDKN2A | 29 NA 0 0 | 87 NA 26.1 47.8 | NA | NA | 39 26.1 0 0 | NA | NA | NA |
Yu et al. (2017) | panc juice | 115 | NGS | TP53 and SMAD4 | 64.7 | NA | NA | NA | NA | 64.7 | 100 | NA |
Kanda et al. (2013) | panc juice | 43 | PCR and Sanger sec | TP53 | 67.4 | NA | NA | NA | NA | 67.4 | 100 | NA |
Cheng et al. (2017) | Plasma | 188 | ddPCR NGS | BRCA2 KDR EGFR ERBB2 KRAS | 11.7 13.8 13.3 13.3 72.3 | NA | NA | NA | NA | NA | NA | ERBB2: OS (HR = 1.61; p = 0.035) KRAS: OS (HR = 1.45; p = 0.019) |
Berger et al. (2018) | Plasma | 20 | NGS and ddPCR | KRAS and TP53 | 80 | 81.8 | NA | NA | NA | 80 | NA | PFS (r = – 0.86; p = 0.01) |
Henriksen et al. (2016) | Plasma | 95 | MSP | 10 genes | NA | NA | NA | NA | NA | 76 | 83 | UICC stages I-II vs. III–IV (AUC = 0.82) |
Liggett et al. (2010) | Plasma | 30 | microarray- mediated methylation | 17 marker panel | NA | NA | NA | NA | NA | 91.2 | 90.8 | NA |
Park et al. (2012) | Plasma | 106 | MSP | mNPTX2 | 80 | NA | NA | NA | NA | 80 | 76 | NA |
Melnikov et al. (2009) | Plasma | 30 | multiplexed array- methylation | mCCND2, mPLAU mSOCS1, mVHL, mTHBS1 | NA | NA | NA | NA | NA | 76 | 59 | NA |
Melson et al. (2014) | Plasma | 30 | MSP | mVHL, mMYF3, mTMS, mGPC3, mSRBC | NA | NA | NA | NA | NA | 81 | 67 | NA |
Eissa et al. (2019) | Plasma | 39 | MSP | mBNC1 | 65.1 | NA | NA | NA | NA | 64.1 | 93.7 | NA |
mADAMTS1 | 87.2 | 87.2 | 95.8 | |||||||||
mBNC1 and mADAMTS1 | 97.4 | 97.4 | 91.6 | |||||||||
Yi et al. (2013) | Serum | 42 | MOB and MSP | mBNC1 | 92 | NA | NA | NA | NA | 79 | 89 | NA |
mADAMTS1 | 68 | 48 | 92 | |||||||||
mBNC1 and mADAMTS1 | NA | 81 | 85 |