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. 2016 Dec 14;8(8):14192–14220. doi: 10.18632/oncotarget.13929

Table 3. Serum markers in HCC.

Marker Function Specificity Sensitivity Correlations Notes
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