Table 4.

Metabolome and metabolomics profiling in hepatocellular carcinoma.

Platform	Sample	Analysis	Metabolites	Related Pathways	Ref.
LC-MS	Urine	PLS-DA, Heat map, ROC curve	Nucleosides, bile acids, citric acid, amino acids, cyclic adenosine monophosphate, glutamine, acylcarnitines	Purine metabolism, energy metabolism, amino acid metabolism	[67]
GC-TOF-MS	Serum	PCA, OPLS-DA, heat map	Phenylalanine, malic acid, 5-methoxytryptamine, palmitic acid, asparagine, b-glutamate	Energy metabolism, macromolecular synthesis, oxidative stress	[76]
GC-MS	Cells	Heat map, loading plots	D-mannitol, D-glucose	Lipid and amino acid metabolism	[77]
LC-MS	Serum	PLS-DA, ROC curves	Xanthine, uric acid, cholyglycine, D-leucic acid, 3-hydroxycapric acid, arachidonyl lysolecithin, dioleoyl phosphatidylcholine	Purine catabolism lipid metabolism	[78]
GC-MS	Plasma	PLS-DA, OPLS-DA	Glutamic acid, citric acid, lactic acid, valine, isoleucine, leucine, alpha tocopherol, cholesterol, sorbose	Branched-chain amino acid metabolism	[79]
GC-MS, UPLC-MS-MS	Serum		12-HETE, 15-HETE, sphingosine, xanthine, amino acids serine, glycine, aspartate, acylcarnitines	Cell regulation, amino acid biosynthesis, neutralization reaction, eicosanoid	[80]
1H-NMR (1D), LC-MS	Serum	PCA, random forests analysis	Formate, tyrosine, ascorbate, oxaloacetate, carnitine, phenylalanine, C16 sphinganine, lysophosphatidylcholines, phosphatidylcholines	Ketone biosynthesis, citric acid cycle, phospholipid, fatty acid oxidation, sphingolipid, amino acid/bile acid metabolism	[81]
GC-MS	Serum Liver tissues	Gene expression	Triglycerides, cholesterol, fatty acids	Lipid metabolism	[82]
LC-MS	Urine	PCA, heat map	Epitestosterone, allotetrahydrocortisol	Steroid hormonal system, steroid hormone pattern	[83]
LC-MS	Serum	Spearman correlation	Phenylalanine, tyrosine, glutamate, kynurenine, tryptophan, biogenic amines	Amino acid, biogenic amine metabolism	[84]
13C-NMR, LC-MS/MS	Tissues	PCA	Alanine, succinate, lactate, glycerophosphoethanolamine, inorganic phosphate, leucine, isoleucine, valine	Aspartate metabolism, tricarboxylic acid metabolism	[85]
LC-MS	Liver	Gene expression	Lysine, phenylalanine, citrulline, creatine, creatinine, inosine, glycodeoxycholic acid, alpha-ketoglutarate, multiple acyl-lyso-phosphatidylcholine	Krebs cycle, urea cycle, amino acid, purine metabolism	[86]
UHPLC-MS	Serum	PCA	Acylcarnitines, fatty acids, phosphatidyl ethanolamine	Fatty acid, b-oxidation, phosphatidylcholine, phosphatidyl ethanolamine metabolism	[87]
CE-TOF/MS	Serum	PCA, PLS-DA, correlation network	Creatine, betaine, kynurenine, pipecolic acid	Fundamental carbon metabolism, glycerolipid digestion, methylation reactions, oxidative stress	[88]
CE-TOF/MS	Serum	PLS-DA, ROC curves, V-plot	Tryptophan, glutamine, and 2-hydroxybutyric acid	Amino acid metabolism	[89]

HPLC, ultra-performance liquid chromatographic; ROC, receiver operating characteristic; PCA, principal component analysis; NMR, nuclear magnetic resonance; MS, mass spectrometry; OPLS-DA, orthogonal PLS-DA; GC, gas chromatography; HPLC: high pressure liquid chromatography; LC, liquid chromatography; CE, capillary electrophoresis; v, volcano.