Table 1.
Summary of all KP research carried out on HCC.
| Author (Year) [Ref] |
Sample Type | Sample Size | Enzyme/Metabolite Studied | Technique Used | Finding |
|---|---|---|---|---|---|
| Ishio et al. (2004) [122] | Cell lines HCC tumour specimens |
4 HCC cell lines 21 HCC |
IDO1 | RT-PCR IHC |
IDO1 expression may play a role in antitumour immune response. |
| Pan et al. (2008) [123] | Cell lines Tumour and distant normal liver tissue |
6 HCC and human normal hepatocytes 138 HCC |
IDO1 | RT-PCR IHC |
HCC cancer cells and surrounding noncancerous tissue express high IDO1 expression. High IDO1 expression is confined to the tumour creating an immune suppressive microenvironment. |
| Li et al. (2018) [124] | Cell lines Tumour tissue |
2 HCC cell lines 112 HCC (HBV) * |
IDO1 | RT-PCR WB IHC and IF |
IDO1 is expressed in HCC cells on stimulation by IFN-γ via the JAK2-STAT1 signalling pathway. High IDO1 expression indicates antitumour immune response. IDO1 is a favourable prognostic indicator. |
| Brown et al. (2018) [125] | Cell lines | 2 HCC cell lines | IDO1 | RT-PCR | IDO1 inhibitors in combination with immune checkpoint inhibitors might be an effective treatment option for HCC patients. |
| Hoffman et al. (2020) [126] |
Cell lines Tumour and normal tissue |
1 HCC cell line 171 tissue specimens |
TDO2 | RT-PCR WB, HPLC IHC and IF |
High TDO2 expression observed in HCC tumour cells. TDO2 may be a novel immunotherapeutic target for HCC. |
| Li et al. (2020) [127] | Cell lines Paired tumour and adjacent normal tissues |
5 HCC cell lines and 1 normal liver cell line 93 HCC |
TDO2 | RT-PCR WB RT-PCR WB, IHC |
TDO2 is overexpressed in HCC and may be facilitating HCC progression and invasion. TDO2 enzyme can be a novel prognostic biomarker for HCC patients. |
| Lei et al. (2021) [87] | Cell lines Paired tumour and adjacent normal tissue |
6 HCC cell lines and 1 normal liver cell 23 HCC |
TDO2 | RT-PCR WB Knockdown using shRNAs HPLC IHC and IF |
TDO2 supports EMT of HCC cells via the KYN-AhR pathway, facilitating HCC metastasis and invasion. |
| Bekki et al. (2020) [128] | Serum | 604 HCC * (HCV) 288 Control ** |
KYN | ELISA | A high level of serum KYN correlated with poor prognosis of HCC. |
| Jin et al. (2015) [129] | Tumour and adjacent noncancerous liver tissue Cell lines |
120 matched HCC and adjacent tissue 205 HCC 5 HCC and 2 human normal liver cells |
KMO | IHC RT-PCR WB Knockdown using siRNAs |
High KMO expression correlated with HCC tumour aggression, recurrence, and shorter survival rate. KMO knockdown suppressed HCC progression in vitro. KMO overexpression enhanced HCC cell proliferation, migration, and invasion. |
* HCC patients with chronic hepatitis B (HBV) or hepatitis C (HCV) virus infection. ** Patients with chronic hepatitis C virus infection without HCC. RT-PCR: reverse transcription-polymerase chain reaction, WB: Western blot, IHC: immunohistochemistry, IF: immunofluorescence, HPLC: high-performance liquid chromatography, shRNA: short hairpin or small hairpin RNA, siRNA: small interfering RNA.