Table 1.
Example of candidate HCC diagnostic biomarkers. Sensitivity, specificity and AUROC shown as percentages (%).
| Biomarker | Type | Study Type | Sensitivity (%) | Specificity (%) | AUROC (%) | Cut-Off | Ref. | Notes |
|---|---|---|---|---|---|---|---|---|
| α-FP | Protein | Systematic review | 4–71 | 29–100 | 65 | 20–500 ng/mL | Tateishi, R. et al., 2008 [178] | Cirrhosis, Viral CLD |
| Protein | Review | 67.7 | 71 | - | >100 ng/mL | Stefaniuk, P. et al., 2010 [19] | Cirrhosis any etiology (HCV and HBV prevalent), CLD | |
| Protein | Metanalysis | 60–65 | 80–84 | NA | 20 ng/mL or 200 ng/mL | Colli, A. et al., 2021 [189] | CLD | |
| α-FP-L3 | Protein | Review | 61.6 | 92 | - | - | Stefaniuk, P. et al., 2010 [19] | Cirrhosis any etiology (HCV and HBV prevalent), CLD |
| Protein | Metanalysis | 34 | 92 | 75 | 3.84–10% | Zhou, J.M. et al., 2021 [190] | HCC | |
| Protein | Prospective | 66.7–73.1 | 82,7 | 79–80 | 10% | Singal, A.G. et al., 2022 [10] | Cirrhosis | |
| Protein | Retrospective | 64.3–67.4 | 94.5–95 | 64–69 | 10% | Tayob, N. et al., 2022 [36] | HCC | |
| DCP | Protein | Metanalysis | 67 | 92 | 89 | 4.5–7.5 ng/mL | Gao, P. et al., 2012 [43] | Cirrhosis any etiology, CLD |
| Protein | Review | 72.7 | 90 | 82 | - | Stefaniuk, P. et al., 2010 [19] | Cirrhosis any etiology (HCV and HBV prevalent), CLD | |
| GP73 | Protein | Retrospective | 62 | 88 | - | 12.69 relative units (HCC); 4.39 relative units (Cirrhosis) | Li, X. et al., 2009 [59] | Cirrhosis any etiology |
| Protein | Prospective | 87.1 | 83.9 | 92 | 7.4 relative units (HBV related HCC) | Hu, J.S. et al., 2010 [60] | CHB | |
| Protein | Metanalysis | 76 | 86 | 88 | 2.36–400 relative units (HCC); 10–113.8 (early HCC) | Zhou, Y. et al., 2012 [61] | Cirrhosis, Viral CLD | |
| GPC-3 | Protein | Retrospective | 84–85 | 92–95 | 85–89 | - | El-Saadany, S. et al., 2018 [68] | HCC |
| OPN | Protein | Metanalysis | 81 | 87 | - | - | Sun, T. et al., 2018 [81,83] | CHB |
| DKK1 | Protein | Prospective | 87.3 | 82.9 | 82.6 | 8.92 ng/mL | Awad, A.E. et al., 2019 [94] | Cirrhotics any etiology (HCV prevalent) |
| Protein | Metanalysis | 71 | 87 | 85 | - | Jiang X et al., 2020 [181] | - | |
| AFU | Protein | Metanalysis | 72 | 88 | 82 | - | Gan Y et al., 2014 [97] | - |
| AXL | Protein | Retrospective | 93.8 | 61.9 | 84 | 1243 pg/mL | Song X., et al., 2020 [100] | CLD any etiology and cirrhotics |
| MDK | Protein | Metanalysis | 85 | 83 | 91 | 0.5 ng/mL | Zhang, Y., et al., 2020 [104] | HCC |
| Protein | Systematic review and metanalysis | 83.5 | 81.7 | 97 | 0.387–1.683 ng/mL | Lu, Q. et al., 2020 [105] | Viral CLD | |
| Protein | Cross-sectional | 100 | 90 | 95 | 5.1 ng/mL | El-Shayeb, A.F. et al., 2021 [106] | Cirrhosis | |
| AKR1B10 | Protein | Prospective | 81 | 61 | 76 | 1.51 ng/mL | Han, C., et al., 2018 [112] | Cirrhosis (HCV and HBV prevalent), CLD |
| ANXA2 | Protein | Prospective | 74 | 88 | 86 | 18 ng/mL | Shaker M.K., et al., 2017 [122] | CLD any etiology and cirrhotics, HBV, HCV and cryptogenetic; Early HCC |
| SCCA | Protein | Retrospective | 41.9 | 82.6 | 70 | 3.8 ng/ml | Giannelli G et al., 2007 [126] | Cirrhosis any etiology, early HCC |
| SCCA-IC | Protein | Retrospective | 52.3 | 75.7 | 67.5 | 104 AU/mL | Giannelli G et al., 2007 [126] | Cirrhosis any etiology, early HCC |
| GS | Protein | Retrospective | 73.6 | 98.2 | 85 | 599.3 ng/mL | Liu P., et al., 2020 [134] | Cirrhosis HBV, ALD |
| Extracellular vesicles chip | Genetic | Retrospective | 94.4 | 88.5 | 93 | - | Sun N et al., 2020 [138] | Early HCC vs Cirrhosis |
| exo-miR-4746-5p | Genetic | Retrospective | 81.8 | 91.7 | 95 | - | Cho H.J. et al., 2020 [191] | Early HCC |
| exo-miR-10b-5p | Genetic | Retrospective | 90.7 | 75 | 93 | - | Cho H.J. et al., 2020 [191] | Early HCC |
| miR-320b, miR-663a, miR-4448, miR-4651, miR-4749-5p, miR-6724-5p, miR-6877-5p, and miR-6885-5p | Genetic | Retrospective | 97.7 | 94.7 | 99 | - | Yamamoto Y. et al., 2020 [192] | Any etiology |
| Circular RNAs | Genetic | Metanalysis | 82 | 82 | 89 | - | Nie, G. et al., 2022 [186] | Cirrhosis any etiology, CLD |
| cg04645914, cg06215569, cg23663760, cg13781744, and cg07610777 | Genetic | Retrospective | - | - | 95 | - | Hlady RA., et al., 2019 [193] | HCC vs non tumour |
| Chemokines | Immunological | Retrospective | 66 (CCL4); 71 (CCL5) | 74 (CCL4); 78 (CCL5) | - | 0.86 ng (CCL4) and 84 pg/mL (CCL5) | Sadeghi M et al., 2015 [165] | Cirrhosis any etiology, CLD |
| IL-6 | Immunological | Metanalysis | 46–73 | 73–95 | 72 | 3–12 pg/mL | Witjes CD et al., 2013 [170] | Any etiology |