Alpha-fetoprotein (AFP) |
Glycoprotein, synthetized during the early stages of fetal liver development. The biological function of AFP is still not well identified. |
76%–94% |
39-65% |
Hepatocyte regeneration, during hepatocarcinogenesis and embryonic carcinomas |
AFP sensitivity and specificity depend on the cut-off value chosen and on population characteristics |
Lens culinaris Agglutinin (LCA) fraction of AFP |
AFP glycoform, characterized by an elevated affinity to lectins such as Lens culinaris agglutinin |
>95% |
51% |
Aggressiveness, poor differentiation, ki-67, distant metastasis |
Sensitivity strictly depends on HCC diameter |
Des-γ-carboxy prothrombin (DCP) |
Abnormal prothrombin derived by an acquired defect in the post-translational carboxylation of the prothrombin precursor in HCC cells |
48-62% |
81-98% |
Poor prognosis, portal vein invasion, intrahepatic metastasis, hepatic vein thrombosis, and capsular infiltration |
A moderate diagnostic accuracy in HCC has been showed |
Glypican-3 (GPC-3) |
Heparan-sulphate proteoglycans. In HCC tissue, it promotes cell growth by stimulating Wnt signaling |
87%-90% |
53%-59% |
|
GPC3 would serve also as a target for therapeutic intervention in HCC |
P-aPKC-i |
Serine-threonine kinases (PKC), important for apico-basal maintenance and cellular junction formation |
|
|
Pathological differentiation, tumor size, invasion, and metastasis |
Studied as tissutal marker more than serum marker |
E-Cadherin |
Transmembrane glycoprotein associated with inhibition of the formation of tight junctions among tumoral cells |
|
|
Development of metastasis; poor tumoral differentiation |
Studied as tissutal marker more than serum marker |
b-Catenin |
Cytoskeleton protein |
|
|
Invasiveness and tendency to metastatization |
Studied as tissutal marker more than serum marker |
Human Carbonyl Reductase 2 |
Cytosolic enzyme involved in detoxification of the compounds derived from oxidative stress |
|
|
|
Studied as tissutal marker more than serum marker |
Vascular Endothelial Growth Factor |
Role in angiogenesis, stimulating the proliferation and migration of endothelial cells and increasing vascular permeability |
85% |
65% |
Portal vein emboli, poorly encapsulated tumors, microscopic vein invasion, and recurrence in HCC patients. Predictor of tumor aggressiveness, DFS, and OS in patients who underwent HCC resection |
Associated with poor outcomes in patients treated with sorafenib, indicating that VEGF could be used as an indicator of clinical efficacy |
Squamous Cell Carcinoma Antigen (SCCA) |
Serin protease inhibitors |
48.9% |
84.2% |
Tumor size |
|
a-l-fucosidase (AFU) |
Lysosomal enzyme involved in degradation of fuco-glycoconjugates |
|
|
PFS, OS, macrovascular invasion |
|
Transforming Growth Factor b1 |
Protein involved in inhibition of cell proliferation and triggering apoptosis |
|
|
Hepatocarcinogenesis and tumor angiogenesis, tumor size, postoperative DFS and OS |
|
Embryonic Liver Fodrin (ELF) |
Adaptor protein involved in TGF-β1 signaling pathway |
|
|
HBsAg, tumor size, TNM and recurrence, postoperative DFS and OS |
|
Golgi protein-73 |
Golgi glycoprotein expressed in epithelial human cells |
75% |
69% |
|
GP73 accuracy was higher than AFP, even if is less suitable for discriminating between primary malignant and benign tumors of the liver |
Serum Anti-p53 |
Antibody directed against p53 |
91.52% |
84.63% |
AFP, tumor size, MELD and Child-Pugh score |
P53 mutations are correlated with poorly differentiated cancer and shorter survival of patients with HCC |
Chromogranin A (CgA) |
Acidic glycoprotein contained in secretory granules of neuroendocrine cells |
|
|
Degree of neuroendocrine differentiation of HCC |
|
Hepatocyte Growth Factor |
Cytokine with wide ranges of effects; it stimulates hepatocyte proliferation including HCC cells through expression of its receptor, the c-met receptor |
|
|
Poor survival |
|
Nervous Growth Factor |
Cytokine involved in cancer growth, invasion and metastatization, in addition to its role in differentiation and survival of neuronal cells |
|
|
|
The mechanism of NGF involvement in liver tissue remodeling processes and HCC remains unclear |