Hepatitis B Virus Pre-S Mutants as Biomarkers and Targets for the Development and Recurrence of Hepatocellular Carcinoma
Abstract
:1. Introduction
2. The Prevalence of Pre-S Mutants in Patients is Gradually Increased from Chronic Hepatitis B (CHB) to Liver Cirrhosis (LC) and Reaches a Peak in HCC
3. The Presence of Pre-S Mutants in Patients with Chronic HBV Infection is Associated with a Higher Risk of LC and HCC Development
4. The Presence of Pre-S Mutants in Patients with HBV-Related HCC Predicts a Higher Risk of HCC Recurrence after Curative Surgical Resection
5. The Expression of Pre-S Mutants Predicts a Higher Risk of HCC Recurrence after Curative Surgical Resection, Even Under Pre-Surgical Anti-HBV Treatment
6. The Oncogenic Signal Pathways Activated by Pre-S Mutants Represent Potential Targets for Chemoprevention of HBV-Related HCC
7. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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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 |
Ref. | Sample Type | Detection Approach | Summary of the Evidence |
---|---|---|---|
Fan et al. [31] | Serum from patients at low, intermediate, and high HBV replicative phases | PCR | Higher prevalence of overall pre-S deletions (including the pre-S1 and/or pre-S2 deletions) at low HBV replicative phase |
Shen et al. [32] | Serum from patients at low, intermediate, and high HBV replicative phases | PCR | Higher prevalence of overall pre-S deletions (including the pre-S1 and/or pre-S2 deletions) at low HBV replicative phase |
Shen et al. [32] | Serum from CHB and HCC patients | PCR | Higher prevalence of overall pre-S deletions (including the pre-S1 and/or pre-S2 deletions) in HCC |
Choi et al. [33] | Serum from CHB, LC, and HCC patients | PCR | Higher prevalence of overall pre-S deletions (including the pre-S1 and/or pre-S2 deletions) in HCC |
Li et al. [34] | Serum from CHB, LC, and HCC patients | PCR | Higher prevalence of overall pre-S deletions (including the pre-S1 and/or pre-S2 deletions) in HCC; predominance of pre-S1 and pre-S2 deletions in LC and HCC, respectively |
Jia et al. [35] | Serum from CHB and nontumorous liver tissues from HCC patients | NGS | Higher prevalence of overall pre-S deletions (including the pre-S1 and/or pre-S2 deletions) in HCC |
Zhao et al. [36] | Plasma | CGE | Higher prevalence of overall pre-S deletions (including the pre-S1 and/or pre-S2 deletions) in HCC; predominance of the pre-S deletions of small size (≤99 base pairs) in HCC |
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Teng, C.-F.; Wu, H.-C.; Su, I.-J.; Jeng, L.-B. Hepatitis B Virus Pre-S Mutants as Biomarkers and Targets for the Development and Recurrence of Hepatocellular Carcinoma. Viruses 2020, 12, 945. https://doi.org/10.3390/v12090945
Teng C-F, Wu H-C, Su I-J, Jeng L-B. Hepatitis B Virus Pre-S Mutants as Biomarkers and Targets for the Development and Recurrence of Hepatocellular Carcinoma. Viruses. 2020; 12(9):945. https://doi.org/10.3390/v12090945
Chicago/Turabian StyleTeng, Chiao-Fang, Han-Chieh Wu, Ih-Jen Su, and Long-Bin Jeng. 2020. "Hepatitis B Virus Pre-S Mutants as Biomarkers and Targets for the Development and Recurrence of Hepatocellular Carcinoma" Viruses 12, no. 9: 945. https://doi.org/10.3390/v12090945