Table 7.

The main results of relevant metabolomic studies on HCC.

Reference	Methods	Sample	Main findings
[43]	RRLC-QTOF-MS	Serum	Tryptophan decreased in the sera of CHB, CIR, and HCC patients; C16:1-CN, as one of the long-chain acylcarnitines, increased with severity of chronic liver diseases.
[44]	UPLC-linear ion trap Q-Orbitrap-MS	Urine	Adenosine, inosine, cyclic AMP, and citric acid increased significantly, while xanthine, MTA, 6-methyladenosinie, CA, GCA, and GCDCS decreased notably in liver diseases than healthy control group. Carnitine C4:0 and hydantoin-5-propionic acid were defined as a combinational marker to distinguish HCC from CIR.
[45]	UPLC-QTOF-MS	Urine	Palmitic acid, alpha-N-phenylacetyl-L-glutamine, phytosphingosine, indoleacetyl glutamine, and glycocholic acid were the most significant differential metabolites for the classification of the HCC and the control.
[46]	UHPLC-LTQ-Orbitrap-MS	Tissue and serum	In liver tissue, there were 880 metabolites that could differentiate hepatocellular carcinoma tissue from distal noncancerous tissue, while in serum, betaine and propionylcarnitine were selected as the optimal combination for diagnosis of hepatocellular carcinoma.
[47]	UPLC-QTOF-MS and UPLC-QqQLIT-MS and UPLC-triple quadrupole-MS	Serum	GCA, GDCA, TCA, and TCDCA were significantly downregulated in sera of HCC versus those with cirrhosis, while lysoPC 17:0 and S-1-P showed a marginally significant upregulation.
[48]	GC-TOF-MS UPLC-QTOF-MS	Serum and urine	Five differential metabolites are found both in serum and urine samples in HCC patients, including glycocholic acid, cysteine, cystine, taurine, and phenylalanine. These metabolites represent bile acid metabolism, methionine metabolism, and phenylalanine and tyrosine metabolism.
[49]	UPLC-LTQ-Orbitrap-MS	Tissue	Betasitosterol, L-phenylalanine, lysoPCs, glycerol-phosphocholine, lysoPEs, enodeoxycholic acid glycine conjugate, and quinaldic acid were significantly lower in central tumor tissue group compared with the distant tissue group. Arachidyl carnitine, tetradecanal, and oleamide were significantly high in the central tumor tissue group compared with the distant tissue group. A comparison of the levels of these metabolites in the adjacent tissue group showed relative closeness to those in the central tumor tissue group.
[50]	CE-TOF-MS	Serum	Four metabolites including tryptophan, glutamine, arginine, and 2-hydroxybutyric acid fulfilled the demand of small HCC discrimination. The combination of Trp, Gln, and 2-hydroxybutyric acid was better to establish the discrimination model for the validation set (including small HCC subjects).
[51]	1H-NMR	Serum	LDL, VLDL, choline, and acetoacetic acid decreased in liver cirrhosis and hepatocellular carcinoma patients, while the contents of glutamine, pyruvate, phenylalanine, and tyrosine increased. These metabolites could differentiate patients from healthy people, but liver cirrhosis and hepatocellular carcinoma partially overlap.
[52]	RRLC-QTOF-MS UPLC-LTQ-Orbitrap-MS	Serum	Six major clusters were observed, the representative characteristic metabolites were selected from each cluster including LPC 22:5, palmitoyl-L-carnitine, LPC 22:6, LPE 16:0, LPC O-16:0, and TCA. Three metabolites including LPC 22:5, LPE 16:0, and TCA were selected as candidate markers for the classification of HCC and chronic liver diseases.

RRLC-QTOF-MS: rapid-resolution liquid chromatography quadrupole time-of-flight mass spectrometry.

UPLC-QqQLIT-MS: ultraperformance liquid chromatography coupled with triple quadrupole linear ion trap mass spectrometry.