Table 2.
Selected growth factors, signaling mediators, and other proteins in HBV-associated HCC prognosis
| Soluble factor | Tissue type | Stage(s) evaluated | mRNA or protein | Conclusion | Supplemental reference(s) |
|---|---|---|---|---|---|
| Ang-2 | Liver | HCC | Protein | Expression in tumor correlates with microvessel density; lower expression correlates with lower recurrence | 1 |
| COX-2 | Liver | HCC | Protein | Expression in tumor correlates with VEGF | 2 |
| CTGF | Liver | HCC | mRNA | Higher in tumor predicts bone metastases, poor survival after resection | 3–5 |
| Serum | Cirrhosis, HCC | Protein | Higher in cirrhotic patients than in HCC patients with cirrhosis, which are higher than healthy controls; decreasing serum levels with advancing HCC | 6 | |
| DKK1 | Serum | Chronic liver disease, HCC | Protein | Higher in HCC patients than chronic liver disease and healthy controls | 7 |
| EGFR | Serum | HCC | Protein | Higher in HCC patients than chronic liver disease and healthy controls, with enhanced levels with co-infection with HBV and HCV | 8 |
| HGF | Serum | Chronic liver disease, HCC | Protein | Higher in HCC and chronic HBV and HCV patients than healthy controls | 9 |
| IGF2 | Liver | Cirrhosis, HCC | Protein | Higher expression in tumor and cirrhotic tissue than in chronic hepatitis or healthy controls; correlates with HBV+ status; P3 transcript overexpressed in HCC, correlates with degree of differentiation, infiltration of serosa, tumor size, and HBV status | 10–16 |
| Serum | HCC | Protein | Higher in HCC patients than healthy controls | 16 | |
| MMP1 | Liver | HCC | Protein | High peritumoral predicts bone metastases | 3 |
| Serum | HCC | Protein | Higher in HCC patients than cirrhotic or healthy controls | 17 | |
| MMP9 | Liver | HCC | Protein | Lower expression correlates with lower recurrence | 1 |
| OPN | Liver | HCC | Protein | Expression in tumor correlates with capsular and venous invasion, lymph node metastasis, and worse prognosis; elevated expression predicts worse disease-free and overall survival | 18, 19 |
| Serum | Cirrhosis, HCC | Protein | Higher in HCC patients than cirrhotic or healthy controls; and both higher than healthy controls, and predictive of liver damage severity; elevated expression predicts tumor size and recurrence | 20–22 | |
| SHH | Liver | Chronic liver disease, HCC | Protein | Higher in HCC and chronic HBV and HCV patients than healthy controls | 23 |
| TGF-α | Liver | HCC | mRNA, protein | Higher expression in tumor and peritumor and in non-neoplastic HBsAg+ tissue than chronic HBV which is higher than in healthy tissue | 24–27 |
| Serum | Chronic liver disease, HCC | Protein | Higher in HCC patients than chronic liver disease and healthy controls | 28 | |
| TGF-β | Liver | HCC | Protein | Higher in HCC patients than healthy controls, higher in HBV+ patients than HBV− patients; higher in groups with tumor embolus of portal vein; higher expression of pSmad2 in HBV+ primary tumors than HBV− primary tumors; higher expression of pSmad2 in metastases than primary tumors | 29–31 |
| Serum | Chronic liver disease, HCC | Protein | Higher in HCC patients than chronic liver disease and healthy controls, with enhanced levels with co-infection with HBV and HCV | 8, 28 | |
| VEGF | Liver | HCC | Protein | Higher in tumor predicts worse clinical outcome | 1, 2, 32, 33 |
| Wnt-1 | Liver | HCC | Protein | Increased expression in HBV+ and HCV+ HCC; intratumoral expression correlated with increased recurrence | 34 |
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