Nuclear magnetic resonance-based metabolomics and metabolic pathway networks from patient-matched esophageal carcinoma, adjacent noncancerous tissues and urine

Table 1 Summary of clinical and demographic features for study subjects and tumor characteristics

	EC	HC	χ2	P value
Subjects, n	41	40
Age (median, range), yr	60, 39-77	59, 28-78
Sex			6.77	0.12
Male	31	19
Female	10	21
Cancer stage
Stage I/II	15	-
Stage III	11	-
Stage IV	15	-
CEA, ng/mL
Positive	2	-
Negative	31	-
Not measured	8	-
CA 19-9, U/mL
Positive	2	-
Negative	18	-
Not measured	21	-
Location
Cervical	1	-
Upper thoracic	5	-
Middle thoracic	24	-
Lower thoracic	11	-
Symptoms
Dysphagia	40	-
Gastroesophageal reflux	27	-

EC: Esophageal cancer; HC: Healthy control; CA 19-9: Carbohydrate antigen 19-9; CEA: Carcinoembryonic antigen.

Table 2 Potential urine biomarkers for discriminating esophageal cancer patients from healthy controls

Metabolite	Chemicalshift, ppm	Fold difference		AUC (95%CI)	Related metabolic pathways
		EC / HC	P value
Acetoacetate	2.25–2.28	1.55 ↑	< 0.001	0.745 (0.636–0.836)	Fatty acid metabolism, TCA cycle
Glutamate	2.04–2.06	1.22 ↑	0.002	0.702 (0.590–0.798)	Glutaminolysis, TCA cycle
Cis-aconitate	3.40–3.46	1.30 ↑	0.001	0.719 (0.608–0.813)	TCA cycle, glyoxylate and dicarboxylate metabolism
Citrate	2.48–2.54 2.64–2.66	1.27 ↑	0.002	0.643 (0.528–0.746)	TCA cycle
Hippurate	7.51–7.56 7.60–7.65 7.78–7.84	0.45 ↓	0.002	0.702 (0.591–0.799)	Gut microflora metabolism
Ethanola-mine	3.08–3.16	0.86 ↓	0.001	0.723 (0.613–0.817)	Fatty acid metabolism
Glycine	3.54–3.55	0.85 ↓	0.003	0.633 (0.518–0.737)	Amino acid metabolism
Creatinine	3.03–3.06 4.05–4.10	0.95 ↓	< 0.001	0.790 (0.685–0.872)	Urea metabolism, Creatinine metabolism
Taurine	3.26–3.28	0.53 ↓	< 0.001	0.763 (0.655–0.850)	Amino acid metabolism
Glucose	3.73–3.80	0.89 ↓	0.007	0.694 (0.581–0.792)	Glycolysis; TCA cycle

EC: Esophageal cancer; HC: Healthy control; AUC: Area under the curve; TCA: Tricarboxylic acid.

Table 3 Potential tissue biomarkers for discriminating esophageal cancer tissue from adjacent noncancerous tissue

Metabolite	Chemicalshift, ppm	Fold difference		AUC (95%CI)	Related metabolic pathways
		ECT / ANT	P value
Valine	0.96–0.99 1.02–1.04	1.63 ↑	< 0.001	0.988 (0.889-1.000)	Amino acid metabolism
Leucine	0.93–0.95	1.32 ↑	< 0.001	0.852 (0.705-0.944)	Amino acid metabolism
Glutamate	1.97–2.08 2.32–2.39	1.30 ↑	< 0.001	0.930 (0.803-0.986)	Glutaminolysis, TCA cycle
Acetate	1.88–1.93	1.33 ↑	0.001	0.790 (0.632-0.902)	SCFA metabolism
Alanine	1.43–1.48	1.44 ↑	< 0.001	0.920 (0.789-0.982)	Amino acid metabolism, Gluconeogenesis
Choline	3.19–3.22	1.59 ↑	< 0.001	0.980 (0.876-1.000)	Choline metabolism, Lipid metabolism
Succinate	2.39–2.40	2.12 ↑	0.009	0.738 (0.575-0.864)	TCA cycle
Citrate	2.68–2.71	1.42 ↑	< 0.001	0.942 (0.820-0.991)	TCA cycle
Glucose	3.37–3.44 3.50–3.52	0.72 ↓	< 0.001	0.928 (0.800-0.985)	Glycolysis, TCA cycle
Creatinine	3.02–3.03 4.04–4.06	0.64 ↓	< 0.001	0.963 (0.849-0.997)	Urea metabolism, Creatine metabolism
Glycine	3.52–3.55	0.75 ↓	< 0.001	0.850 (0.702-0.943)	Amino acid metabolism
Threonine	3.58–3.62	0.60 ↓	< 0.001	0.933 (0.806-0.987)	Amino acid metabolism
Creatine	3.90–3.94	0.78 ↓	< 0.001	0.917 (0.786-0.981)	Urea metabolism, Creatine metabolism
Glutamine	2.42–2.48	0.77 ↓	< 0.001	0.895 (0.757-0.969)	Glutaminolysis, TCA cycle
Taurine	3.24–3.28 3.33–3.34	0.78 ↓	< 0.001	0.878 (0.735-0.960)	Amino acid metabolism

ANT: Adjacent noncancerous tissue; ECT: Esophageal cancer tissue; AUC: Area under the curve; TCA: Tricarboxylic acid.