Table 1.
Different biomarkers of ctDNA for HCC
| Patients | Controls | Ethnicity | Sample | Sample vol. | Biomarkers | Biomarker Type | Positive Rate (%) | Supplement information | Ref. |
|---|---|---|---|---|---|---|---|---|---|
| 24 | 62 (HBV) | China | Plasma | 1ml | Concentration | CfDNA level | - | - | 25 |
| 31 | 8 (CLD) | China | Plasma | - | CNVs & SNVs | CNVs | - | - | 26 |
| 34 | 0 | China | Plasma | - | CNV | CNVs | - | CNVs correlating to tumor burden | 27 |
| 151 | 14 (HV) |
Korea | Plasma | 1.5ml | VEGFA & CNV |
Amplication & CNVs |
- | - | 28 |
| 90 | 67 (CLD) 36 (LC) 32 (HV) |
China | Plasma | 3-4.8 ml | CfDNA size | Integrity | - | - | 29 |
| 53 | 16 (OLT) | China | Plasma | 1ml | Plasma DNA integrity | Integrity | - | ALU as primer | 30 |
| - | - | China | Plasma | 4ml | Preferred plasma DNA end coordinates | Integrity | - | - | 31 |
| 27 | 0 | Asia, Europe, USA |
Plasma | - | RAS (KRAS & NRAS); | Mutation | 44.4 | Evaluated for RAS mutational status by BEAMing firstly | 32 |
| TERT | Mutation | 63.0 | |||||||
| TP53 | Mutation | 48.1 | |||||||
| CTNNB1 | Mutation | 37.0 | |||||||
| 66 | 35 (LC) 41 (CLD) |
Italy | Plasma | 200ul | TERT | Mutation | - | - | 33 |
| 7 | 0 | Europe | Plasma | 3-6ml | TERT TP53 CTNNB1 TSC1 RB1 APOB et al. |
Mutation | 86 | The large tumor was>5 cm or metastatic HCC |
34 |
| 23 | 0 | 9 | The small (largest tumor<5 cm), nonmetastatic HCC | ||||||
| 66 | 0 | China | Plasma | 5ml | TP53 CTNNTB1 AXIN1 ARID1A |
Mutation | 60 15.7 14.3 14.3 |
- | 35 |
| 51 | 10 (LC) | UK & Italy | Plasma | - | ARID1A CTNNB1 TP53 |
Mutation | 11.7 7.8 7.8 |
- | 36 |
| 29 | 0 | China | Plasma | 1.5-1.8ml | TP53 ATM ALK NPM1 CSF1R KIT ERBB4 SMAD4 FBXW7 PTEN |
Mutation | 50 39 36 36 36 32 32 29 29 |
- | 37 |
| 33 | 0 | China | Plasma | 5-6ml | TP53 CTNNB1 AXIN1 JAK1 EPS15 CACNA2D4 |
Mutation | 52-84 | - | 38 |
| 206 | 0 | USA | Plasma | 5-6ml | TP53 EGFR MET ARID1A MYC NF1 BRAF ERBB2 |
Mutation & Amplification |
0.49 (range 0.06 - 55.03%) | median mutant allele frequency (% cfDNA) | 24 |
| 26 | 0 | USA | Plasma | - | 5hmC | Methylation | - | - | 39 |
| 25 | 90 (HV) | China | Plasma | 2ml | 5hmC | Methylation | 44 | - | 40 |
| 1204 | 392 (CLD or LC) 958 (HV and BT) |
China | Plasma | 3-6ml | 5hmC | Methylation | - | validation set: area under curve (AUC)=88.4% | 41 |
| 29 | 32 (HV) 8 (HBV) |
USA | Plasma | 5ml | multiple CpG sites | Methylation | 94.8 | - | 42 |
| 36 | 38 (HV;LC; CLD) | China | Serum | 2ml | RGS10 ST8SIA6 RUNX2 VIM |
Methylation | 94 | - | 43 |
| 51 | 186 (LC) | France | Plasma | 3.5ml | SEPT9 | Methylation | 94.1 | Initial Study | 44 |
| 47 | 103 (LC) | Germany | 85.1 | Replication Study | |||||
| 66 | 43 (CLD) | United States | Serum | 1-2ml | INK4A | Methylation | 65 | - | 45 |
| 8 | 8 (HV) | France | Plasma | 1ml | VIM | Methylation | 2.3 | - | 46 |
| FBLN1 | - | ||||||||
| 32 | 38 (HV) | France | Plasma | 1ml | VIM | Methylation | 1.48 | Odds ratios | 47 |
| FBLN1 | 0.89 | ||||||||
| 22 | 16 (CLD) 28 (HV) |
Thailand | Plasma | 1ml | VIM | Methylation | 2.18 | ||
| FBLN1 | 0.75 | ||||||||
| 31 | 27 (HV) 31 (HBV) |
China | Serum | - | DBX2 | Methylation | 88 | - | 48 |
| THY1 | 85 | ||||||||
| 160 | 88 (CLD) 45 (HV) |
China | Serum | 400ul | TGR5 | Methylation | 48 | - | 49 |
| 121 | 37 (CLD) 31 (HV) |
China | Serum | 400ul | MT1M | Methylation | 84 | - | 50 |
| MT1G | Methylation | 70 | |||||||
| 715 | 560 (HV) | China | Plasma | 1.5ml | BMPR1A, PSD, ARHGAP25, KLF3, PLAC8, ATXN1, Chr 8:20, Chr 6:170, Chr 6:3, ATAD2 |
Methylation | 85.7 | Diagnostic Panel | 51 |
| 1049 | - | China | Plasma | 1.5ml | SH3PXD2A, C11orf9, PPFIA1, SERPINB5, Chr 17:78, NOTCH3, GRHL2, TMEM8B |
Methylation | - | Prognostic prediction Panel |
Different kinds of biomarkers have been used to detect ctDNA from normal cfDNA, including cfDNA level, DNA copy number, gene integrity, gene mutations, and DNA methylation alterations. In the past 5 years of ctDNA biomarker research, DNA methylation has become a research hotspot, followed by genetic mutation.