TABLE 1.
Summary of biomarkers in use and in development
| Mechanism | Use | Sensitivity, % | Specificity, % | Phase of development | Reference | |
|---|---|---|---|---|---|---|
| Serum Biomarkers | ||||||
| AFP (cutoff 20 ng/mL) | Glycoprotein secreted by the adult liver in inflammatory states (ie, chronic HBV or HCV) Linked to the growth of HCC and evasion of intrinsic anti-tumor mechanisms Up to 20% of HCC are non-AFP producing |
Early detection, response to treatment AFP > 400 ng/mL is a poor prognostic indicator- ramicurumab effective in this population |
39–64 | 76–97 | Phase V | 7,8 |
| AFP-L3% | Subfraction of AFP | Early detection | 62 | 90 | Phase III | 9,10 |
| DCP | Prothrombin variant produced by HCC; levels vary with vitamin K levels | Early detection | 40 | 81 | Phase III | 9,10 |
| Liquid biopsy techniques | ||||||
| CTC | HCC tumor cells that enter the peripheral circulation | Early detection, Response to treatment | 95 | 73 | Phase III | 11 |
| cfDNA | Peripherally circulating nucleic acids released with cell turnover/apoptosis in malignant and inflammatory states | Early detection, Response to treatment | 91–96.8 | 43–98.8 | Phase II, III | 12–15 |
| cfRNA | Coding and noncoding RNA segments circulating in peripheral blood associated with tumor progression | Response to treatment | Variable depending on RNA segment | Variable depending on RNA segment | Phase III | 16 |
| DNA methylation markers | Changes in methylation patterns of HCC oncogenes and tumor suppressor genes | Response to treatment | Variable depending on gene | Variable depending on gene | Phase II | 15 |
| Extracellular vesicles | Membrane vesicles released by cells in both normal physiologic and pathologic states; contain bioactive molecules that can act at nearby or distant sites and are often involved in tumor growth | Early detection | 70–89 | 47–82 | Phase III | 17 |
| Clinical algorithms | ||||||
| GALAD | Gender, age, AFP-L3%, AFP, DCP | Early detection | 54–72 | 90 | Phase III published; Phase IV/V in progress | 3 |
| Doylestown Plus | AFP, age, gender, alkaline phosphatase, alanine aminotransferase | Early detection | 90 | 95 | Phase III | 18 |
| HCC early detection screening algorithm | AFP, rate of AFP change, age, alanine aminotransferase, platelets | Early detection | 53 | 48 | Phase II-III | 10 |
Abbreviations: AFP, alpha-fetoprotein; CfDNA, cell-free DNA;CfRNA, Cell-free RNA; CTC, circulating tumor cells; DCP, Des-γ-carboxy prothrombin; GALAD, Gender, Age, AFP-L3, AFP, and DCP.