Table 1.
The roles of pre-S mutants as biomarkers and targets for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) development and recurrence.
| I. Biomarkers | |||
|---|---|---|---|
| Ref. | Sample Type | Detection Approach | Summary of the Evidence |
| Chen et al. [19] | Serum | PCR | Higher risk of HCC development in patients with pre-S deletions (either or both of pre-S1 and pre-S2 deletions) |
| Sinn et al. [20] | Serum | PCR | Higher risk of HCC development in patients with pre-S deletions (either or both of pre-S1 and pre-S2 deletions) |
| Tsai et al. [21] | Nontumorous liver tissues | IHC staining | Higher risk of HCC recurrence after curative surgical resection in patients with the type II GGHs (pre-S2 deletions; score 2–4) |
| Li-Shuai et al. [22] | Serum | PCR | Higher risk of HCC recurrence after curative surgical resection in patients with pre-S deletions, especially in patients with the pre-S2 deletions only |
| Yen et al. [23] | Serum | Pre-S Gene Chip | Higher risk of HCC recurrence after curative surgical resection in patients with the pre-S2 deletions (≥5%) |
| Teng et al. [24] | Plasma | NGS | Higher risk of HCC recurrence after curative surgical resection in patients with either deletions spanning the pre-S2 gene segment or high percentage of pre-S2 plus pre-S1 + pre-S2 deletions (>24.995%) or both factors |
| Tsai et al. [25] | Nontumorous liver tissues | IHC staining | Higher risk of HCC recurrence after curative surgical resection in patients with the type II GGHs (pre-S2 deletions; score 3–4) even under pre-surgical anti-HBV treatment |
| II. Targets | |||
| Ref. | Mouse Model | Treatment | Summary of the Evidence |
| Teng et al. [26] | Transgenic mice expressing both pre-S2 mutant and HBx proteins | Combination of resveratrol and silymarin | Suppression of HCC formation through inhibition of mTOR-dependent glycolysis pathways |
| Teng et al. [27] | Transgenic mice expressing both pre-S2 mutant and HBx proteins | Phytosome-formulated curcumin | Suppression of HCC formation through activation of PPARγ and inhibition of NF-κaB and mTOR activation |
Abbreviations: PCR, polymerase chain reaction; IHC, immunohistochemistry; NGS, next-generation sequencing; HCC, hepatocellular carcinoma; GGHs, ground glass hepatocytes; HBx, hepatitis B virus X; mTOR, mammalian target of rapamycin; PPARγ, peroxisome proliferator-activated receptor γ; NF-κB, nuclear factor-κB.