Serum metabolome profiles characterized by patients with hepatocellular carcinoma associated with hepatitis B and C

Table 1 Clinical characteristics of the study subjects

	Hepatitis B-associated HCC(n = 30)	Hepatitis C-associated HCC(n = 38)	P value
Sex (M/F)	28/2	22/16	< 0.011
Age (yr)	62.6 ± 10.9	73.4 ± 9.7	< 0.012
Albumin (g/dL)	3.4 ± 0.6	3.4 ± 0.5	NS2
Total bilirubin (mg/dL)	1.2 ± 0.6	1.4 ± 1.3	NS2
AST (U/L)	75.6 ± 76.2	57.8 ± 31.6	NS2
ALT (U/L)	54.3 ± 38.4	49.8 ± 38.3	NS2
Fasting blood glucose (mg/dL)	104.5 ± 22.2	113.1 ± 36.0	NS2
γ-glutamyl transferase (U/L)	77.0 ± 64.8	60.4 ± 58.1	NS2
Creatinine (mg/dL)	0.73 ± 0.19	1.01 ± 1.53	NS2
Platelet count (× 103/μL)	13.5 ± 8.4	11.7 ± 4.7	NS2
Fib-4 index	5.7 ± 4.4	6.4 ± 3.9	NS2
AFP (ng/mL) ≤ 6.2 /> 6.2	10/20	8/30	NS1
DCP (mAU/mL) ≤ 40 /> 40	17/13	24/14	NS1
HBs antigen, positive	30	0
HCV-antibody, positive	0	38
HBV genotype (A/B/C/D)	0/14/15/1	NA
HCV genotype (1b/2a/2b)	NA	34/4/0

¹Fisher exact test;

²Mann-Whitney U-test. Data were expressed as mean ± SD. AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; NS: Not significant; NA: Not applicable; DCP: Des-γ-carboxy prothrombin; HCC: Hepatocellular carcinoma.

Table 2 Parameters of multiple logistic regression model

Metabolite	Coefficient	95%CI		Odds ratio	95%CI		P value
(Intercept)	-8.01	-14.0	-4.14				1.00 × 10-3
Met	0.0521	0.018	0.0979	1.05	1.02	1.10	8.60 × 10-3
γ-Glu-Gly-Gly	-17.6	-35.7	-5.31	2.23 × 10-8	3.18 × 10-16	4.93 × 10-3	1.97 × 10-2
Glu	0.0255	0.0135	0.0454	1.03	1.01	1.05	1.30 × 10-3

Met: Methionine; Glu: Glutamic acid; γ-Glu-Gly-Gly: γ-glutamyl-glycine-glycine.

Table 3 Correlation coefficients between amino acids and γ-glutamyl peptides

Amino acid	γ-glutamyl peptides	Spearman R	95%CI	P value(two-tailed)
Ile	γ-Glu-Ile	0.4584	0.2401-0.6325	< 0.0001
Ala	γ-Glu-Ala	0.04022	-0.4898	0.7447
Ser	γ-Glu-Ser	0.2117	-0.4698	0.0831
Val	γ-Glu-Val	0.4565	0.2379-0.6311	< 0.0001
Thr	γ-Glu-Thr	0.3909	0.1610-0.5805	0.001
Leu	γ-Glu-Leu	0.4898	0.2779-0.6562	< 0.0001
Asn	γ-Glu-Asn	0.4012	0.1729-0.5885	0.0007
Lys	γ-Glu-Lys	0.2909	0.04915-0.5004	0.0161
Gln	γ-Glu-Gln	0.6387	0.4665-0.7642	< 0.0001
Glu	γ-Glu-Glu	0.8268	0.7294-0.8913	< 0.0001
His	γ-Glu-His	0.2982	0.05714-0.5064	0.0135
Phe	γ-Glu-Phe	0.4886	0.2765-0.6554	< 0.0001
Arg	γ-Glu-Arg	0.4258	0.2016-0.6076	0.0003
Tyr	γ-Glu-Tyr	0.6937	0.5404-0.8024	< 0.0001
Asp	γ-Glu-Asp	0.5566	0.3606-0.7056	< 0.0001
Met	γ-Glu-Met	0.5418	0.3420-0.6947	< 0.0001
Trp	γ-Glu-Trp	0.3433	0.1070-0.5428	0.0042
Gly	γ-Glu-Gly	0.05704	-0.489	0.6441
Gly	γ-Glu-Gly-Gly	0.006012	-0.4905	0.9612