Disease monitoring of hepatocellular carcinoma through metabolomics

Table 2 Significantly altered metabolites in cirrhosis patients vs healthy volunteers

Ref.	Platform	Tissue (organism)	Significantly altered metabolites in cirrhosis patients vs healthy volunteers	Main pathways distinguishing cirrhosis from healthy volunteers
Gao et al[33]	1H NMR	Serum (human)	Isoleucine ↓	Amino acid metabolism
			Leucine ↓
			Valine ↓
			Glutamine ↑
			Tyrosine ↑
			Phenylalanine ↑
			1-methylhistidine ↑
			N-acetylglycoproteins ↑
			Acetate ↑	N-acetylglycoprotein
			Acetoacetate ↓	Ketonogenesis
			Pyruvate ↑
			α-ketoglutarate ↑	Glycolysis
			Choline ↓	TCA cycle
			Taurine ↑
			Glycerol ↑	Bile acid metabolism
Li et al[42]	UPLC/QTOF-MS	Serum (mouse)	Leucine ↓	Amino acid metabolism
			Phenylpyruvic acid ↓
			Phenylalanine ↓
			Tryptophan ↓
			LPE (16:0) ↓	LPE metabolism
			LPE (18:0) ↓
			LPC (16:0) ↓	LPC metabolism
			LPC (20:1) ↓
			LPC (22:6) ↑
			PC (16:0/18:3) ↑	Phosphatidylcholine metabolism
			PC (12:1/24:3) ↑
			PC (16:0/20:4) ↑
			PC (16:0/22:6) ↑
			PC (18:0/20:4) ↑	Sphingomyelin metabolism
			SM (d18:0/16:1) ↓
Soga et al[35]	Capillary elecrtophore-sis/TOF-MS	Serum (human)	γ-glutamylalanine ↑	Glutathione metabolism
			γ-glutamylvaline ↑
			γ-glutamylglutamine ↑
			γ-glutamylphenyl-
			γ-glutamylcitrulline ↑
			Alanine ↑	Amino acid metabolism
			Methionine sulfoxide ↑
Wang et al[38]	UPLC/MS-MS; LC/QTOF-MS	Serum (human)	LPC-16:0 ↓	LPC metabolism
			LPC-18:0 ↓
			16:0/18:1-PC ↓
			16:0/18:2-PC ↓
			16:0/20:4-PC ↓
			16:0/22:6-PC ↓
			18:0/18:2-PC ↓
			Oleamide ↑	Fatty acid metabolism
			Phenylalanine ↑
			GCDCA ↑	Bile acid metabolism
			Canavaninosuccinate ↓	Arginosuccinate synthetase pathway
Zhou et al[39]	UPLC/QTOF-MS	Serum (human)	Phenylalanine ↑	Amino acid metabolism
			GCA ↑	Bile acid metabolism
			GDCA ↑
			Bilirubin ↑	Hemoglobin metabolism
			LPE (18:2) ↓	Lysolipid metabolism
			LPC (22:6) ↓
			LPC (18:2) ↓
			LPC (20:4) ↓
			LPC (16:0) ↓
			LPC (18:0) ↓
			C18:1-CN ↑	CPT shuttle system
Chen et al[30]	UPLC/QTOF-MS	Serum (human);	Inositol ↓	TCA cycle
		Urine (human)	2,2-bipyridine ↓
			Methionine ↓	Amino acid metabolism
			Tyrosine ↓
			Arginine ↓	Fatty acid metabolism
			Stearic acid ↓
			Palmitic acid ↓
			Citric acid ↓
			2-piperidine carboxylic acid ↓
			5-Hydroxy-tryptophan ↓
Cao et al[32]	UPLC/MS	Fecal (human)	Chenodeoxycholic	Bile acid metabolism
			Acid dimeride ↓
			Urobilin ↓	Hemoglobin metabolism
			Urobilinogen ↓
			7-ketolithocholic acid ↓	Microbiome metabolism
			LPC C18:0 ↑	LPC metabolism
			LPC C16:0 ↑
Yin et al[41]	RPLC/MS	Serum (human)	Hypoxanthine ↓	Purine synthesis
			Inosine ↓
			Bilirubin ↑	Hemoglobin metabolism
			GCA ↑	Bile acid metabolism
			GCDCA ↑
			Taurine ↓
			LPC C18:2 ↓	LPC metabolism
			LPC C18:3 ↓
			LPC C16:1 ↓
			LPC C18:0 ↓
			LPC C16:1 ↓
			L-acetylcarnitine ↑	CPT shuttle system
			6-Methylnicotinic acid ↓	Nicotine metabolism
Fitian et al[45]	Integrated UPLC/MS-MS and GC/MS	Serum (human)	Glycocholate (GCA) ↑	Bile acid metabolism
			Tauroursodeoxycholate ↑
			Glychochemodeoxycholate ↑
			Azelate (nonanedioate) ↑	Dicarboxylic acid metabolism
			Undecanedioate ↑
			Sebacate (decanedioate) ↑
			Hexadecanedioate↑
			Tetradecanedioate↑
			DSGEGDFXAEGGGVR ↑	Fibrinogen cleavage peptide
			ADSGEGDFXAEGGGVR ↑
			Bilirubin (Z,Z) ↑	Hemoglobin catabolism metabolite
			Biliverdin ↑
			1,2-propanediol ↑	Ketogenesis
			Succinylcarnitine ↑	CPT shuttle system
			Acetylcarnitine ↑
			Glutarylcarnitine ↑
Gao et al[46]	GC-TOF/MS	Serum (human)	Palmitic acid ↑	Fatty acid metabolism
			Stearic acid ↑
			Oleic acid ↑
			Arachidic acid ↑	Arachidonic acid metabolism
			Aminomalonic acid ↑	Dicarboxylic acid metabolism
			Phenylalanine ↑	Amino acid metabolism
			Cysteine ↑
			Leucine ↑
			Citric acid ↑
			Oxoproline ↑

EtOH: Alcohol; TOCSY: Total correlation spectroscopy; HH: Hereditary hemochromatosis; TCA: Tricarboxylic acid; UPLC: Ultrahigh-performance liquid chromatography; QTOF: Quadrupole time of flight; SELDI: Surface-enhanced laser desorption/ionization; HRMAS: High-resolution magic angle spinning; LPE: Lysophosphatidyethanolamine; LPC: Lysophosphatidylcholine; MS: Mass spectrometry; TOF: Time-of-flight; NMR: Nuclear magnetic resonance; LC: Liquid chromatography; GC: Gas chromatography; CPT: Carnitine palmitoyltransferase; TCA: Tricarboxylic acid.