Table II. Summary of the differentially expressed serum and urine metabolites in patients of HCC (all stages) relative to healthy controls. An empty cell in the table means the alteration of metabolite level is statistically insignificant. G: data obtained from GC-TOFMS, P: data obtained from positive ion mode of UPLC-QTOFMS, N: data obtained from negative ion mode of UPLC-QTOFMS.
| Metabolites | Metabolic pathway | HCC (Serum) |
HCC (Urine) |
||||
|---|---|---|---|---|---|---|---|
| VIPc | Pd | FC ± S.D.e | VIPc | Pd | FC ± S.D.e | ||
| Deoxycholic acid, N | Bile acid metabolism | 1.49 | 2.43E-03 | 0.36 ± 0.1 | |||
| Glycochenodeoxycholic acida N | Bile acid metabolism | 1.53 | 1.80E-03 | 6.67 ± 1.59 | |||
| Glycocholic acida,‖P | Bile acid metabolism | 1.18 | 3.52E-03 | 6.4 ± 1.66 | 0.63 | 9.33E-04 | 45 ± 14.96 |
| Taurocholic acidaN, € | Bile acid metabolism | 1.17 | 1.87E-02 | 25.36 ± 6.41 | |||
| Lithocholic acidaP | Bile acid metabolism | 0.12 | 1.45E-02 | 0.93 ± 0.21 | |||
| Arachidonic acid,G | Fatty acid metabolism | 1.44 | 5.38E-08 | 0.84 ± 0.01 | |||
| cis-5,8,11,14, 17-Eicosapentaenoic acidaP | Fatty acid metabolism | 1.68 | 5.70E-04 | 0.43 ± 0.08 | |||
| Docosahexaenoic acida,bG | Fatty acid metabolism | 1.27 | 2.43E-06 | 0.82 ± 0.03 | |||
| Glycerol,G | Fatty acid metabolism | 1.16 | 2.00E-05 | 0.85 ± 0.02 | |||
| Myristic acidaN | Fatty acid metabolism | 1.84 | 1.45E-04 | 0.66 ± 0.06 | |||
| Nervonic acida,bN | Fatty acid metabolism | 1.39 | 4.75E-03 | 0.56 ± 0.09 | |||
| Alaninea,bG | Methionine Metabolism | 2.12 | 2.68E-02 | 0.71 ± 0.09 | |||
| Cysteinea,b‖G | Methionine Metabolism | 1.29 | 1.81E-06 | 1.25 ± 0.03 | 1.57 | 3.34E-03 | 0.35 ± 0.12 |
| Cystinea,b‖G | Methionine Metabolism | 1.91 | 1.54E-14 | 1.44 ± 0.04 | 1.09 | 4.34E-02 | 1.32 ± 0.11 |
| GlycineaG | Methionine Metabolism | 1.01 | 2.37E-04 | 0.86 ± 0.02 | |||
| Serinea,bG | Methionine Metabolism | 1.16 | 2.06E-05 | 0.84 ± 0.02 | |||
| TaurineaP | Methionine Metabolism | 0.91 | 2.48E-02 | 1.45 ± 0.15 | 1.35 | 1.22E-02 | 1.43 ± 0.13 |
| Aspartic acida,bG | Urea cycle | 1.26 | 3.06E-06 | 0.89 ± 0.01 | |||
| Citrulline.bG | Urea cycle | 1.51 | 9.47E-09 | 0.87 ± 0.01 | |||
| Glutamic acida,b G | Urea cycle | ||||||
| Ornithinea,b G | Urea cycle | 1.55 | 3.55E-09 | 0.96 ± 0.03 | |||
| Fumaric acidaG | TCA cycle | 1.39 | 2.17E-07 | 1.28 ± 0.04 | |||
| Succinic acid,G | TCA cycle | 1.97 | 4.02E-02 | 0.63 ± 0.12 | |||
| α−Ketoglutaric acid,G | TCA cycle | 1.18 | 1.58E-05 | 1.11 ± 0.01 | |||
| Lactic acida,bG | Glycolysis | 1.08 | 7.97E-05 | 1.16 ± 0.03 | |||
| Pyruvic acidbG | Glycolysis | 1.26 | 3.46E-06 | 1.18 ± 0.03 | |||
| 4-Hydroxyphenylacetate,G | Gut flora metabolism | 1.39 | 4.51E-02 | 0.69 ± 0.13 | |||
| Trimethylamine N-oxideaP | Gut flora metabolism | 1.74 | 1.09E-03 | 0.54 ± 0.07 | |||
| Kynureninea,bG | Tryptophan Metabolism | 1.24 | 4.76E-06 | 0.77 ± 0.03 | |||
| Tryptophana,bG | Tryptophan metabolism | 1.12 | 4.00E-05 | 0.76 ± 0.03 | |||
| DopamineaP | Tyrosine Metabolism | 2.2 | 2.53E-05 | 1.64 ± 0.11 | |||
| Homovanillate,G | Tyrosine Metabolism | 2.73 | 4.10E-03 | 0.65 ± 0.06 | |||
| NormetanephrineaP | Tyrosine Metabolism | 1.48 | 5.69E-03 | 0.44 ± 0.12 | |||
| AdenineaP | Purine Metabolism | 1.45 | 7.09E-03 | 0.44 ± 0.1 | |||
| AdenosineaP | Purine Metabolism | 1.92 | 2.97E-04 | 1.6 ± 0.11 | |||
| Hypoxanthinea,bP,€ | Purine Metabolism | 1.42 | 8.18E-03 | 1.42 ± 0.13 | |||
| Inosinea,bN | Purine Metabolism | 0.93 | 1.27E-10 | 40.62 ± 19.37 | |||
| Uric acidaP | Purine Metabolism | 1.5 | 5.15E-03 | 1.61 ± 0.16 | |||
| XanthineaP | Purine Metabolism | 1.64 | 2.18E-03 | 1.61 ± 0.16 | |||
| Carnosine,P | Histidine Metabolism | 1.28 | 1.81E-02 | 0.83 ± 0.04 | |||
| Lysinea,bG | Lysine Degradation | 1.32 | 8.93E-07 | 0.79 ± 0.03 | |||
| Nicotinic acidaP | Nicotinate and Nicotinamide Metabolism | 1.33 | 1.37E-02 | 0.24 ± 0.1 | |||
| Glucosamine,G | Amino Sugar Metabolism | 1.53 | 6.16E-09 | 0.62 ± 0.03 | |||
| N-Acetyl-l-Aspartic acidaP | Aspartate metabolism | 1.09 | 4.38E-02 | 1.37 ± 0.14 | |||
| d-(+)-galactose,G | Galactose Metabolism | ||||||
| Pyroglutamic acidaN | Glutathione Metabolism | 0.88 | 1.53E-03 | 0.9 ± 0.02 | |||
| Phenylalaninea,b‖G | Phenylalanine and Tyrosine Metabolism | 1.06 | 1.22E-04 | 0.85 ± 0.02 | 1.41 | 8.64E-03 | 1.26 ± 0.07 |
| CytidineaN | Pyrimidine Metabolism | 1.02 | 4.05E-02 | 0.55 ± 0.13 | |||
| DihydrouracilaP | Pyrimidine Metabolism | 2 | 1.50E-04 | 1.41 ± 0.07 | |||
| Cysteic acida,bP | Taurine Metabolism | 1.84 | 5.33E-04 | 0.4 ± 0.05 | |||
| HypotaurineP | Taurine Metabolism | 1.55 | 3.89E-03 | 1.53 ± 0.16 | |||
| Threoninea,bP | Threonine metabolism | 2.34 | 7.18E-06 | 1.77 ± 0.13 | |||
| Leucinea,bN | Valine, Leucine and Isoleucine Degradation | 1.21 | 1.45E-02 | 0.83 ± 0.05 | |||
| β-alaninea,bG € | β-Alanine Metabolism | 0.85 | 2.45E-03 | 0.8 ± 0.05 | |||
| PyridoxalaP | Vitamine | 1.33 | 1.32E-02 | 1.99 ± 0.32 | |||
| α-tocopherolaG | Vitamine | 1.37 | 3.19E-07 | 0.96 ± 0 | |||
| 2,3-dihydroxy-2(3H)-furanone,G | Others | 1.63 | 3.37E-10 | 1.43 ± 0.04 | |||
| 2,3-dihydroxyl-propanoic acid,G | Others | 1.93 | 6.53E-15 | 0.79 ± 0.02 | |||
| 2-pyrrolidone-5-carboxylic acidaP | Others | 1.2 | 2.65E-02 | 0.52 ± 0.11 | |||
| 3-amino-2-piperidoneaG | Others | 1.56 | 2.71E-09 | 0.85 ± 0.01 | |||
| 4-ketoglucose,G | Others | 1.74 | 8.19E-12 | 0.6 ± 0.03 | |||
| 6-Aminocaproic acidaP | Others | 2.36 | 5.49E-06 | 0.09 ± 0.02 | |||
| AgmatineaP | Others | 1.38 | 1.06E-02 | 1.5 ± 0.17 | |||
| Arabinose,G | Others | 1.98 | 6.70E-16 | 0.45 ± 0.03 | |||
| CarnitineaP | Others | 1.39 | 5.16E-04 | 1.36 ± 0.07 | |||
| Creatininea,bG | Others | 1.6 | 8.81E-10 | 0.77 ± 0.02 | |||
| CreatineaP, € | Others | 2 | 1.49E-04 | 0.46 ± 0.07 | |||
| N-Acetyl-neuraminic acidaP | Others | 2.29 | 1.08E-05 | 2.43 ± 0.26 | |||
| OleamideΔ,G | Others | 2.67 | 7.62E-48 | 0.7 ± 0.01 | |||
| O-Phospho-l-serineaP | Others | 1.22 | 2.33E-02 | 1.36 ± 0.11 | |||
| Phosphoric acid,G | Others | 1.48 | 2.36E-08 | 0.88 ± 0.01 | |||
a Metabolites validated by reference standards.
b Metabolites that can be identified by GC-TOFMS and UPLC-TOFMS.
c Variable importance in the projection (VIP) was obtained from OPLS with a threshold of 1.0.
d P means p value obtained from Student's t-test.
e The Fold change (FC) with a value larger than 1.0 indicates a significantly higher level of the serum or urine metabolite in patients while a FC value lower than 1.0 indicates a lower level, relative to healthy controls.