Table 1. Marker metabolites found in OPLS-DA models of ¹H NMR-based urine metabolic profiling between I/II stage of CRC and healthy controls.

Top 16 most significant in order	Chemical shift (ppm)	I/II stage of CRC vs healthy controls			Related metabolomic pathway
		VIPa	p-valueb	Variations vs HC
Choline	3.19(s)	2.25	0.000	↓	Choline metabolism, Lipid metabolism
Phenylalanine	3.19(m) 3.98(dd)	2.25 1.43	0.000 0.004	↓ ↓	Amino acid metabolism, Phenylalanine metabolism
Asparagine	2.80(dd)	1.90	0.000	↓	Urea metabolism, Amino acid metabolism
Isocitrate	3.98(d)	1.84	0.005	↓	TCA cycle
Cysteine	3.97(dd) 3.06(m)	1.84 1.70	0.003 0.000	↓ ↓	Amino acid metabolism, Glutamate Metabolism, Glutathione Metabolism
Hippurate	3.96(d)	1.84	0.005	↓	Gut microflora metabolism
Dimethyl sulfone	3.138(s)	1.72	0.000	↓	Gut microflora metabolism, Endogenous methanethiol metabolism
Creatinine	3.03(s) 4.05(s)	1.70 1.43	0.007 0.003	↓ ↓	Urea metabolism, Creatinine metabolism
Alanine	1.46(d)	1.67	0.017	↓	Amino acid metabolism, Gluconeogenesis
Methylamine	2.59(s)	1.12	0.018	↓	Gut microflora metabolism, Disulfiram Pathway
Homocysteine	2.14(m)	1.76	0.014	↑	Amino acid metabolism, Methionine metabolism
Glutamine	2.12(m) 3.76(t)	1.76 1.53	0.001 0.017	↑ ↑	Glutaminolysis, TCA cycle
cis-Aconitate	3.43(d)	1.64	0.043	↑	TCA cycle, Glyoxylate, Dicarboxylate metabolism
Acetoacetate	2.27(s) 3.43(s)	1.59 1.64	0.009 0.043	↑ ↑	Fatty acid metabolism, TCA cycle
trans-Aconitate	3.74(s)	1.54	0.019	↑	TCA cycle
Guanidoacetate	3.78(s)	1.53	0.017	↑	Urea metabolism

a: Variable importance in the projection (VIP) was obtained from OPLS-DA with a threshold of 1.0.

b: p value was calculated from Mann-Whitney U test.