Table 1. . Utility of cfDNA and ctDNA for diagnosis and prognosis in hepatocellular carcinoma.
| Technique | Diagnosis | Prognosis | Clinical association |
|---|---|---|---|
| cfDNA levels | ✓ | ✓ | Higher in HCC compared with chronic liver disease and healthy controls [40–44]; shorter overall survival; distant metastases postresection [42]; tumor differentiation; tumor size [43,61]; 3-year DFS [61] |
| DNA integrity index | ✓ | ✓ | Long fragments more common HCC compared with healthy controls; shorter overall survival; tumor size; TMN stage; vascular and lymphatic invasion; metastases [46] |
| Relative telomere length | ✓ | Longer in HCC compared with chronic liver disease and healthy controls [47] | |
| Copy number variations | ✓ | More common in HCC compared with healthy controls [28] | |
| TP53 249 Ser mutation | ✓ | More common in HCC compared with chronic liver disease and healthy controls [44,50–52] | |
| Deletion chromosome 8 | ✓ | More common in HCC compared with healthy controls [62] | |
| RASSf1A methylation | ✓ | More common in HCC compared with chronic liver disease and healthy controls [25,26,54–56] | |
| p15 methylation | ✓ | More common in HCC compared with chronic liver disease and healthy controls [25,27] | |
| p16 methylation | ✓ | More common in HCC compared with chronic liver disease and healthy controls [25,27] | |
| APC methylation | ✓ | More common in HCC compared with healthy controls [27] | |
| FHIT methylation | ✓ | More common in HCC compared with healthy controls [27] | |
| E cadherin methylation | ✓ | More common in HCC compared with healthy controls [27] | |
| TGR5 methylation | ✓ | More common in HCC compared with chronic liver disease and healthy controls [58] | |
| LINE1 methylation | ✓ | ✓ | Hypomethylation in HCC compared with liver cirrhosis and healthy controls [59]’ shorter overall survival; HBV infection; tumor size; high CLIP score [59] |
| Microsatellite instability marker D8S258 | ✓ | Shorter overall survival and 3-year DFS; tumor stage; tumor differentiation; vascular invasion [62] | |
| Microsatellite instability marker D8S264 | ✓ | Shorter overall survival and 3-year DFS [62] | |
cfDNA: Circulating free DNA; ctDNA: Circulating free tumor DNA; DFS: Disease-free survival; HCC: Hepatocellular carcinoma.