Differences in elongation of very long chain fatty acids and fatty acid metabolism between triple-negative and hormone receptor-positive breast cancer

Yamashita, Yuji; Nishiumi, Shin; Kono, Seishi; Takao, Shintaro; Azuma, Takeshi; Yoshida, Masaru

doi:10.1186/s12885-017-3554-4

Table 2 Evaluation of metabolite pathways in breast cancer and the corresponding normal breast tissue samples

From: Differences in elongation of very long chain fatty acids and fatty acid metabolism between triple-negative and hormone receptor-positive breast cancer

A
Pathway	Biochemical name	Log2-fold (Breast cancer/Normal breast)	p-value	FDR-adjusted p-value
Glycolysis	G1P (glucose-1-phosphate)	−0.280	0.261	0.315
	G6P (Glucose-6-phosphate)	−0.370	0.065	0.076
	F6P (Fructose-6-phosphate)	−0.071	0.837	0.809
	FBP (fructose-1,6-bisphosphate)	0.190	0.470	0.688
	GAP (Glyceraldehyde-3-phosphate)	−0.261	0.163	0.327
	PEP (Phosphoenol-pyruvate)	0.087	0.925	0.829
	Pyruvic acid	−0.058	0.487	0.788
	Lactic acid	1.828	<0.0001	<0.0001
TCA cycle	Pyruvic acid	−0.058	0.487	0.788
	Lactic acid	1.828	<0.0001	<0.0001
	Acetyl-CoA	0.043	0.921	0.902
	Oxaloacetic acid	−0.364	0.134	0.031
	Citric acid	−0.009	0.307	0.962
	cis-Aconitic acid	1.028	<0.0001	<0.0001
	Isocitric acid	0.382	0.016	0.036
	2-Ketoglutaric acid	−0.791	<0.0001	<0.0001
	Succinic acid	−0.954	<0.0001	<0.0001
	Fumaric acid	0.071	0.617	0.789
	Malic acid	0.103	0.436	0.660
Glutamine pathway	L-Glutamate	1.404	<0.0001	<0.0001
	L-Glutamine	1.650	<0.0001	<0.0001
	GABA	0.109	0.890	0.696
Choline pathway	Choline	0.913	<0.0001	<0.0001
	Phosphocholine	2.784	<0.0001	<0.0001
	Betaine	2.256	<0.0001	<0.0001
Urea cycle	L-Asparate	0.636	<0.0001	<0.0001
	Fumaric acid	0.071	0.617	0.787
	L-Arginine	1.314	<0.0001	<0.0001
	L-Ornithine	−0.120	0.766	0.660
	L-Citrulline	0.925	<0.0001	<0.0001
	Uric Acid	−0.073	0.185	0.667
Tryptophan cycle	L-Tryptophan	−0.792	<0.0001	<0.0001
	L-Kynurenine	−0.079	0.404	0.754
	Anthranilic acid	−0.313	0.291	0.372
Glutathione cycle	GSH	0.732	0.012	0.017
	GSSG	−0.148	0.505	0.705
	gamma-L-Glutamylcysteine	0.084	0.800	0.799
	Glycine	2.388	<0.0001	<0.0001
	L-Cysteine	0.271	0.065	0.150
Purine pathway	Guanine	0.093	0.355	0.688
	Guanosine	1.449	<0.0001	<0.0001
	Hypoxanthine	1.448	<0.0001	<0.0001
	Xanthine	0.165	0.315	0.447
	Adenine	−0.027	0.837	0.9480
	Adenosine	0.301	0.035	0.200
Pyrimidine pathway	Cytidine	−0.073	0.660	0.787
	Cytosine + Histamine	−0.213	0.212	0.269
	beta-Alanine	1.664	<0.0001	<0.0001
	Thymine	0.043	0.908	0.910
	Uridine	0.926	<0.0001	<0.0001
Amino acid metabolism	Glycine	2.388	<0.0001	<0.0001
	L-Arginine	1.314	<0.0001	<0.0001
	L-Asparate	0.636	<0.0001	<0.0001
	L-Asparagine	0.524	<0.0001	0.0025
	L-Cysteine	0.271	0.065	0.150
	L-Cystine	−0.260	0.217	0.338
	L-Lysine	1.203	<0.0001	<0.0001
	L-Glutamine	1.650	<0.0001	<0.0001
	L-Glutamate	1.404	<0.0001	<0.0001
	L-Histidine	0.719	<0.0001	0.00080
	L-Isoleucine	1.597	<0.0001	<0.0001
	L-Leucine	1.386	<0.0001	<0.0001
	L-Methionine	1.016	<0.0001	<0.0001
	L-Phenylalanine	1.493	<0.0001	<0.0001
	L-Proline	1.714	<0.0001	<0.0001
	L-Serine	1.484	<0.0001	<0.0001
	L-Threonine	1.261	<0.0001	<0.0001
	L-Tryptophan	−0.792	<0.0001	<0.0001
	L-Tyrosine	1.271	<0.0001	<0.0001
	L-Valine	1.267	<0.0001	<0.0001
B
Pathway	Biochemical name	Log2-fold (TN/EP + H-)	p-value	FDR-adjusted p-value
Glycolysis	G1P (glucose-1-phosphate)	0.463	0.092	0.689
	G6P (Glucose-6-phosphate)	0.090	0.685	0.931
	F6P (Fructose-6-phosphate)	0.821	0.005	0.040
	FBP (fructose-1,6-bisphosphate)	−0.665	0.330	0.689
	GAP (Glyceraldehyde-3-phosphate)	0.641	0.036	0.511
	PEP (Phosphoenol-pyruvate)	0.743	0.095	0.643
	Pyruvic acid	−0.148	0.555	0.906
	Lactic acid	0.302	0.272	0.689
TCA cycle	Pyruvic acid	−0.148	0.555	0.906
	Lactic acid	0.302	0.272	0.689
	Acetyl-CoA	−0.140	0.883	0.931
	Oxaloacetic acid	0.461	0.077	0.511
	Citric acid	−0.272	0.420	0.770
	cis-Aconitic acid	0.200	0.474	0.781
	Isocitric acid	−0.058	0.598	0.937
	2-Ketoglutaric acid	0.155	0.657	0.906
	Succinic acid	−0.825	0.011	0.511
	Fumaric acid	−0.277	0.419	0.707
	Malic acid	0.330	0.228	0.689
Glutamine pathway	L-Glutamate	0.557	0.005	0.045
	L-Glutamine	−0.281	0.242	0.689
	GABA	0.483	0.007	0.689
Choline pathway	Choline	0.491	0.041	0.511
	Phosphocholine	0.032	0.779	0.937
	Betaine	−0.448	0.978	0.835
Urea cycle	L-Asparate	0.091	0.697	0.931
	Fumaric acid	−0.277	0.419	0.707
	L-Arginine	−0.301	0.399	0.770
	L-Ornithine	−0.009	0.906	0.979
	L-Citrulline	0.243	0.130	0.906
	Uric Acid	0.221	0.305	0.906
Tryptophan cycle	L-Tryptophan	0.182	0.182	0.906
	L-Kynurenine	0.377	0.157	0.689
	Anthranilic acid	−1.492	0.020	0.066
Glutathione cycle	GSH	−0.488	0.291	0.770
	GSSG	0.289	0.304	0.718
	gamma-L-Glutamylcysteine	−0.261	0.254	0.835
	Glycine	0.333	0.144	0.689
	L-Cysteine	0.379	0.102	0.689
Purine pathway	Guanine	−0.075	0.935	0.931
	Guanosine	−0.130	0.683	0.906
	Hypoxanthine	0.277	0.201	0.689
	Xanthine	0.046	0.978	0.937
	Adenine	−0.901	0.467	0.740
	Adenosine	−0.570	0.214	0.689
Pyrimidine pathway	Cytidine	−0.268	0.710	0.835
	Cytosine + Histamine	0.212	0.493	0.835
	beta-Alanine	0.078	0.618	0.931
	Thymine	−0.842	0.310	0.689
	Uridine	0.111	0.697	0.906
Amino acid metabolism	Glycine	0.333	0.144	0.689
	L-Arginine	−0.301	0.399	0.770
	L-Asparate	0.091	0.697	0.931
	L-Asparagine	0.008	0.849	0.979
	L-Cysteine	0.379	0.102	0.689
	L-Cystine	0.160	0.775	0.927
	L-Lysine	−0.058	0.964	0.937
	L-Glutamine	−0.281	0.242	0.689
	L-Glutamate	0.557	0.005	0.045
	L-Histidine	0.426	0.235	0.689
	L-Isoleucine	0.172	0.177	0.931
	L-Leucine	0.047	0.389	0.937
	L-Methionine	0.128	0.257	0.931
	L-Phenylalanine	0.046	0.508	0.937
	L-Proline	0.085	0.474	0.937
	L-Serine	−0.042	0.935	0.937
	L-Threonine	0.304	0.441	0.689
	L-Tryptophan	0.182	0.182	0.906
	L-Tyrosine	0.055	0.474	0.937
	L-Valine	0.269	0.071	0.770
C
Pathway	Biochemical name	Log2-fold (TN/Normal breast)	p-value	FDR-adjusted p-value
Glycolysis	G1P (glucose-1-phosphate)	−0.428	0.594	0.510
	G6P (Glucose-6-phosphate)	−0.230	0.699	0.665
	F6P (Fructose-6-phosphate)	0.394	0.357	0.422
	FBP (fructose-1,6-bisphosphate)	−0.606	0.835	0.607
	GAP (Glyceraldehyde-3-phosphate)	−0.006	0.939	0.990
	PEP (Phosphoenol-pyruvate)	1.241	0.030	0.072
	Pyruvic acid	−0.231	0.341	0.656
	Lactic acid	2.501	<0.0001	<0.0001
TCA cycle	Pyruvic acid	−0.231	0.341	0.656
	Lactic acid	2.501	<0.0001	0.001
	Acetyl-CoA	0.361	0.516	0.646
	Oxaloacetic acid	0.112	0.840	0.821
	Citric acid	−0.104	0.665	0.856
	cis-Aconitic acid	1.428	0.003	0.0060
	Isocitric acid	0.669	0.479	0.248
	2-Ketoglutaric acid	−0.760	0.112	0.076
	Succinic acid	−1.624	0.003	0.0017
	Fumaric acid	−0.078	0.921	0.872
	Malic acid	0.570	0.132	0.263
Glutamine pathway	L-Glutamate	1.673	<0.0001	<0.0001
	L-Glutamine	1.631	<0.0001	<0.0001
	GABA	0.321	0.371	0.402
choline pathway	Choline	1.493	0.002	0.0073
	Phosphocholine	2.442	<0.0001	<0.0001
	Betaine	2.357	<0.0001	0.011
Urea cycle	L-Asparate	0.587	0.175	0.318
	Fumaric acid	−0.078	0.921	0.872
	L-Arginine	0.917	0.006	0.027
	L-Ornithine	−0.515	0.471	0.340
	L-Citrulline	1.217	<0.0001	0.010
	Uric Acid	−0.016	0.665	0.656
Tryptophan cycle	L-Tryptophan	−0.785	0.040	0.045
	L-Kynurenine	0.194	0.559	0.713
	Anthranilic acid	−1.739	0.112	0.130
Glutathione cycle	GSH	0.969	0.143	0.263
	GSSG	−0.443	0.188	0.327
	gamma-L-Glutamylcysteine	−0.436	0.270	0.646
	Glycine	2.790	<0.0001	<0.0001
	L-Cysteine	0.621	0.046	0.063
purine pathway	Guanine	0.150	0.689	0.745
	Guanosine	1.680	<0.0001	<0.0001
	Hypoxanthine	2.389	<0.0001	<0.0001
	Xanthine	0.079	0.708	0.872
	Adenine	−0.229	0.663	0.844
	Adenosine	−0.125	0.689	0.826
Pyrimidine pathway	Cytidine	−0.567	0.215	0.263
	Cytosine + Histamine	−0.343	0.373	0.452
	beta-Alanine	1.814	<0.0001	<0.0001
	Thymine	−0.426	0.897	0.665
	Uridine	1.072	0.012	0.028
Amino acid metabolism	Glycine	2.790	<0.0001	<0.0001
	L-Arginine	0.917	0.006	0.027
	L-Asparate	0.587	0.175	0.318
	L-Asparagine	0.809	0.035	0.064
	L-Cysteine	0.621	0.046	0.063
	L-Cystine	−0.039	0.840	0.235
	L-Lysine	1.094	0.012	0.021
	L-Glutamine	1.631	<0.0001	<0.0001
	L-Glutamate	1.673	<0.0001	<0.0001
	L-Histidine	1.056	0.040	0.084
	L-Isoleucine	1.723	<0.0001	0.00016
	L-Leucine	1.479	0.003	0.0073
	L-Methionine	1.219	0.006	0.0030
	L-Phenylalanine	1.426	0.002	0.0099
	L-Proline	2.017	0.002	0.0012
	L-Serine	1.474	0.002	0.0079
	L-Threonine	1.492	0.0011	0.0073
	L-Tryptophan	−0.785	0.040	0.035
	L-Tyrosine	1.383	<0.0001	0.00026
	L-Valine	1.458	<0.0001	0.00015
D
Pathway	Biochemical name	Log2-fold (EP + H- /Normal breast)	p-value	FDR-adjusted p-value
Glycolysis	G1P (glucose-1-phosphate)	−0.222	0.422	0.559
	G6P (Glucose-6-phosphate)	−0.404	0.131	0.083
	F6P (Fructose-6-phosphate)	−0.440	0.185	0.068
	FBP (fructose-1,6-bisphosphate)	0.345	0.525	0.548
	GAP (Glyceraldehyde-3-phosphate)	−0.417	0.054	0.128
	PEP (Phosphoenol-pyruvate)	−0.113	0.653	0.814
	Pyruvic acid	−0.095	0.473	0.712
	Lactic acid	1.683	<0.0001	<0.0001
TCA cycle	Pyruvic acid	−0.095	0.473	0.712
	Lactic acid	1.683	<0.0001	<0.0001
	Acetyl-CoA	−0.055	0.804	0.866
	Oxaloacetic acid	−0.412	0.241	0.049
	Citric acid	0.070	0.330	0.805
	cis-Aconitic acid	0.884	<0.0001	<0.0001
	Isocitric acid	0.377	0.044	0.078
	2-Ketoglutaric acid	−0.810	<0.0001	<0.0001
	Succinic acid	−0.720	<0.0001	<0.0001
	Fumaric acid	0.079	0.982	0.775
	Malic acid	0.045	0.997	0.854
Glutamine pathway	L-Glutamate	1.266	<0.0001	<0.0001
	L-Glutamine	1.719	<0.0001	<0.0001
	GABA	−0.058	0.171	0.854
choline pathway	Choline	0.731	<0.0001	0.00033
	Phosphocholine	2.218	<0.0001	<0.0001
	Betaine	2.313	<0.0001	<0.0001
Urea cycle	L-Asparate	0.658	0.0005	0.00065
	Fumaric acid	0.079	0.982	0.775
	L-Arginine	1.467	<0.0001	<0.0001
	L-Ornithine	−0.058	0.859	0.854
	L-Citrulline	0.945	<0.0001	<0.0001
	Uric Acid	−0.146	0.131	0.775
Tryptophan cycle	L-Tryptophan	−0.946	<0.0001	<0.0001
	L-Kynurenine	−0.134	0.324	0.643
	Anthranilic acid	−0.287	0.442	0.567
Glutathione cycle	GSH	0.645	0.126	0.078
	GSSG	−0.078	0.677	0.854
	gamma-L-Glutamylcysteine	0.132	0.759	0.742
	Glycine	2.290	<0.0001	<0.0001
	L-Cysteine	0.228	0.213	0.364
purine pathway	Guanine	0.204	0.131	0.406
	Guanosine	1.444	<0.0001	<0.0001
	Hypoxanthine	1.336	<0.0001	<0.0001
	Xanthine	0.097	0.495	0.742
	Adenine	−0.120	0.738	0.805
	Adenosine	0.555	0.012	0.032
Pyrimidine pathway	Cytidine	0.016	0.965	0.941
	Cytosine + Histamine	−0.273	0.239	0.275
	beta-Alanine	1.668	<0.0001	<0.0001
	Thymine	0.034	0.970	0.935
	Uridine	0.981	<0.0001	<0.0001
Amino acid metabolism	Glycine	2.290	<0.0001	<0.0001
	L-Arginine	1.467	<0.0001	<0.0001
	L-Asparate	0.658	0.0005	0.00065
	L-Asparagine	0.472	0.005	0.032
	L-Cysteine	0.228	0.213	0.364
	L-Cystine	−0.298	0.274	0.495
	L-Lysine	1.270	<0.0001	<0.0001
	L-Glutamine	1.719	<0.0001	<0.0001
	L-Glutamate	1.266	<0.0001	<0.0001
	L-Histidine	0.763	<0.0001	<0.0001
	L-Isoleucine	1.575	<0.0001	<0.0001
	L-Leucine	1.366	<0.0001	<0.0001
	L-Methionine	1.064	<0.0001	<0.0001
	L-Phenylalanine	1.640	<0.0001	<0.0001
	L-Proline	1.663	<0.0001	<0.0001
	L-Serine	1.506	<0.0001	<0.0001
	L-Threonine	1.313	<0.0001	<0.0001
	L-Tryptophan	−0.946	<0.0001	<0.0001
	L-Tyrosine	1.270	<0.0001	<0.0001
	L-Valine	1.245	<0.0001	<0.0001

The levels of metabolites in the breast cancer tissue samples and the corresponding normal breast tissue samples were analyzed using LC/MS, and then evaluations based on the glycolytic pathway, TCA cycle, glutamine pathway, choline pathway, urea cycle, tryptophan cycle, glutathione cycle, purine pathway, pyrimidine pathway, and amino acid metabolism were evaluated. The results for each metabolite are shown as A: Log2-fold values for the breast cancer tissue samples vs. the corresponding normal breast tissue samples; B: Log2-fold values for the TN tumors vs. the EP + H- tumors; C: Log2-fold values for the TN tumors vs. the corresponding normal breast tissue samples; and D: Log2-fold values for the EP + H- tumors vs. the corresponding normal breast tissue samples. The Wilcoxon signed-rank test was used for comparisons of metabolite levels between the pairs of breast cancer tissue samples and normal breast tissue samples, and the Mann-Whitney U-test was used for comparison involving the metabolites that were not detected in the paired samples. The false discovery rate (FDR)-adjusted p values were also calculated

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