Supplementary materials for manuscript

Metabolic features of the tumormicroenvironment of gastric cancer and the link to the systemicmacroenvironment

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Text S-1The inclusion or exclusion criteria of the clinical patients in this study

Table S-1 The information of the volunteer patients

Table S-2 The low-molecular-weight compounds identified in gastric cancer tissue and blood plasma

Figure S-1 General clustering of tissue and plasma samplesof GC and CSG

a: A PCA scores plot gives an overview of the data set and shows complete separation of tissue samples(■) and plasma samples(□).

b: A supervised PLS-DA scores plot shows better the clustering of different groups.

Figure S-2 A 3-dimensional PLS-DA scores plot of the GC plasma, post-operation GC plasma and the CSG controls plasma.

Text S-1 The inclusion or exclusion criteria of the clinical patients in this study

The inclusion or exclusion of the patients in the study was assessed based on the data available.

Inclusion criteria included:

(1)aged between 30 and 60, both male or female;

(2)definite diagnosis pathologically and gastroscopically;

(3)the post-operation GC patients were performed surgery operation for at least 4 weeks, but not exceed 6 weeks.

Exclusion criteria were:

(1)metabolic disease, such as hyperlipoidemia, diabetes mellitus, gout;

(2)pregnant of lactating female;

(3)any symptom of acute disease during the last 2 weeks, such as: febrile, cough, headache, diarrhoea, hematuria;

(4)momentous stress reaction during the last 2 weeks, such as psychic trauma and a large area of empyrosis;

(5)hematopathy, including all types of leukemia and anaemia;

(6)use of specific drugs during the last 2 weeks, such as antibiotic (quinolones, torlamician), hormone (deoxycortisone, dexamethasone), nonsteroid anti-inflammatory drugs (NSAIDs; acenterine, saridon, contac), among others;

(7)medical treatments before blood collection, such as radiotherapy, chemotherapy.

Table S-1 The information of the volunteer patients

Characteristic / CSG / GC / GC_p
Gender
Male / 11 / 12 / 9
Female / 9 / 5 / 6
Age(years)
Mean±SD / 37.1±12.2 / 41.3±15.1 / 42.9±12.6
Range / 25-56 / 22-58 / 25-60
Drinking﹡ / - / - / -
Smoking / - / - / -
Taking medicine* / - / - / -
H.pylori infection / + / + / +

*not during the last week

Table S-1The low-molecular-weight compounds identified in gastric cancer tissue and blood plasma

Identified compounds / Derivatives / Retention Index
Alanine / N,O-2TMS / 1127
N-Acetylglutamate / O-2TMS / 1542
2-Aminoadipate / N,O-3TMS / 1731
Aminomalonate / N,O-3TMS / 1486
2-Amino-phosphorate / N,O-4TMS / 1805
Arachidonic acid / O-TMS / 2376
Ascorbic acid / O-2TMS / 1876
Aspartate / N,O-3TMS / 1488
Aspartate / N,O-3TMS / 1544
Butyamine / N-2TMS / 1124
Cholesterol / O-TMS / 3188
Citrate / O-4TMS / 1843
Creatinine / N,O-3TMS / 1570
Cysteine / N,S,O-3TMS / 1571
Cystine / N,O-4TMS / 2322
Decanoic acid / O-TMS / 1462
2,5-Diaminovalerolactam / N-2TMS / 1468
2,6-Dihydroxy-9H-purine / N,O-3TMS / 2044
Docosahexaenoic acid / O-TMS / 2567
Fructose-6-phosphate / O-6TMS / 2364
Fumarate / O-2TMS / 1356
N-formyl-Glycine / N,O-2TMS / 1388
Galactofuranose-6-phosphate / O-7TMS / 2618
D-Galactono-1,4-lactone / O-4TMS / 1989
Glucose / MEOX, O-5TMS / 1927
Glucose, pentakis / O-5TMS / 2016
Glutamate / N,O-3TMS / 1634
Glutamine / N,O-4TMS / 1610
Glutamine / N,O-4TMS / 1755
Glutamine / N,O-3TMS / 1790
Glycerate / O-3TMS / 1347
Glycerol-3-phosphate / O-4TMS / 1788
Glycine / N,O-3TMS / 1320
Heptanoic acid / O-TMS / 1188
Hexadecanoic acid / O –TMS / 2048
9-(Z)-Hexadecenoic acid / O –TMS / 2029
-Hydroxybutyrate / O-2TMS / 1180
Hypoxanthine / N,O-2TMS / 1821
1H-Indole-3-propanoic acid / N,O-2TMS / 2099
Lactate / O-2TMS / 1083
Lactose / MEOX, 8TMS / 2764
Leucine / N,O-2TMS / 1287
Linoleic acid / O-TMS / 2217
Lysine / N,O-3TMS / 1722
Lysine / N,O-4TMS / 1942
Lysine / N,O-3TMS / 2082
Malate / O-3TMS / 1503
Maltose / MEOX, 8TMS / 2817
Methionine / N,O-2TMS / 1531
S-methyl-Cysteine / N,O-2TMS / 1434
-D-Methylglucopyranoside / O-4TMS / 2067
Monomethylphosphate / O-2TMS / 1199
Myo-Inositol / O-6TMS / 2129
Myo-Inositol-1-phosphate / O-7TMS / 2471
1-Monopalmitin / O-2TMS / 2601
1-monostearin / O-2TMS / 2795
Oleic acid / O-TMS / 2222
Ornithine / N,O-3TMS / 1629
Ornithine / N,O-4TMS / 1838
Phenylalanine / N,O-2TMS / 1641
Phosphate / O-3TMS / 1295
Proline / N,O-2TMS / 1309
Proline / N,O-2TMS / 1594
Pyroglutamate / O-2TMS / 1534
Ribose / MEOX,O-4TMS / 1707
Robitol / O-4TMS / 1739
Serine / N,O-3TMS / 1377
Stearic acid / O-TMS / 2246
Succinate / O-2TMS / 1324
Sucrose / O-8TMS / 2708
Taurine / N,O-3TMS / 1687
Threonate / O-4TMS / 1584
Threonine / N,O-3TMS / 1403
Alpha-Tocopherol / O-TMS / 3162
gamma-Tocopherol / O-TMS / 3017
Tryptophan / N,O-3TMS / 2245
Tyrosine / N,O-3TMS / 1960
Uracil / O-2TMS / 1351
Urate / N,O-4TMS / 2131
Urea / N-3TMS / 1202
Urea / N-2TMS / 1275
Uridine / O-3TMS / 2480
Valine / N,O-2TMS / 1233

Altogether, 79 compounds were identified. Compounds are identified as TMS, trimethylsilylated, and MEOX, methoxymated derivatives. Identification was confirmed by comparing the mass spectra and retention indices with the authentic references standards and those available in the National Institute of Standards and Technology (NIST) library 2.0 (2005), an in-house mass spectra library database established by the Umeå Plant Science Center(Umea, Sweden), and key lab of drug metabolism and pharmacokinetics, China Pharmaceutical University.

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Figure S-1 General clustering of tissue and plasma samples

a: A PCA scores plot gives an overview of the data set and shows complete separation of tissue samples(■) and plasma samples(□).

b: A supervised PLS-DA scores plot shows better the clustering of different groups.

Figure S-2 A 3-dimensional PLS-DA scores plot of the GC plasma, post-operation GC plasma and the CSG controls plasma. Post-operation GC plasma showed difference from GC plasma and was not overlapping with the CSG control, indicating the metabolic phenotype of post-operation GC plasma did not restore completely.

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