Metabolomics in cancer research: Supplementary data 1 Supplementary Data 2 Supplementary methods 3 Additional information regarding the search strategy used in the main paper 4 Supplementary tables 5 Supplementary Table 1: List of reported metabolites to be altered in human cancers 6 Supplementary figures 7 Supplementary Figure 1: General overview over the metabolomics workflow 8 1 Metabolomics in cancer research: Supplementary data 9 Supplementary methods 10 Search strategy 11 The search strategy was described in the main paper. For the Web of Knowledge search an 12 additional refinement step was necessary to reduce irrelevant findings. The following research 13 areas of low relevance were excluded: 14 Plant Science, Biophysics, Agriculture, Environmental Sciences Ecology, Microbiology, 15 Computer Science, Mathematics, Cardiology, Engineering, Automation control Systems, 16 Marine Freshwater Biology, Behavioral Science, Physics, Developmental Biology, Zoology, 17 Psychiatry, Energy Fuels, Infectious Disease, Parasitology, Mycology, Rheumatology, 18 Psychology, Veterinary Sciences, Dentistry, Legal Medicine, Polymer Science, 19 Anesthesiology, Robotics, Sports Science, Forestry, Tropical Medicine, Virology, Water 20 Resources, Electrochemistry, Evolutionary Biology, Fisheries, Materials Science, 21 Oceanography, Substance Abuse, Geology, Nuclear Science Technology, Operations 22 Research Management, Orthopedics, Allergy, Biodiversity, Educational Research, 23 Metallurgy, Optics, Emergency Medicine, Geochemistry, History philosophy of science, 24 Mathematical methods in Social sciences, Mechanics, Social Issues, Thermodynamics 25 Additionally the abstracts had to contain one of the following keywords: 26 “MS” OR “mass spectrometry” OR “patients”. 2 Metabolomics in cancer research: Supplementary data 27 Supplementary tables 28 Supplementary Table 1: List of reported metabolites altered in human cancers. Metabolites in bold were reported from a study that validated 29 findings within an independent study population. For these validated findings the type of cancer was also listed. Moreover hits in the HMDB for 30 abnormal concentrations of these metabolites in other pathological conditions were reported. Metabolite KEGG ID Metabolic class, pathway or comment Cancer Reported Disease endpoints associated (only validated studies) Frequency with altered concentrations (HMDB) Tryptophan C00078 Amino acid Bladder, RCC, Breast, 18 Various (>5 diseases) CRC, Nasopharyngeal, Ovarian Phenylalanine C00079 Amino acid Ovarian 16 Phenylketonuria + various (>5 diseases) Lactate C00186 Glycolysis Nasopharyngeal 16 Various (>5 diseases) Tyrosine C00082 Amino acid Bladder, RCC, CRC, 16 Various (>5 diseases) Nasopharyngeal Glutamate C00217 Amino acid Breast 15 Various (>5 diseases) Carnitines1 C00318 Carnitines Bladder, RCC, CRC, 15 Not assigned for group of Ovarian metabolites Glycine C00037 Amino acid Breast, 14 Various (>5 diseases) Nasopharyngeal Valine C00183 Amino acid 14 Serine C00065 Amino acid Nasopharyngeal 13 Various (>5 diseases) Palmitic acid C00249 Fatty acid RCC 13 N/A Glucose C00031 Sugar RCC 12 Diabetes + various hormonal imbalances Cysteine C00097 Amino acid CRC 12 Multiple sclerosis, stroke, peripheral neuropathy, dementia, AIDS Fumarate C00122 TCA cycle CRC, RCC 12 Fumaric academia, lung cancer 3 Metabolomics in cancer research: Supplementary data Metabolite KEGG ID Metabolic class, pathway or comment Cancer Reported Disease endpoints associated (only validated studies) Frequency with altered concentrations (HMDB) Threonine C00188 Amino acid 12 Lysophosphocholines1 - Bladder, RCC, Ovarian 11 Not assigned for group of metabolites Myo-inositol C00137 Second messenger RCC 11 Proline C00148 Amino acid Nasopharyngeal 11 Various (>5 diseases) Glutamine C00303 Amino acid 11 Malate C00497 TCA cycle Breast, RCC 11 Anoxia Pyroglutamate C01879 Glutamate derivative Breast 11 Various (>5 diseases) Leucine C00123 Amino acid 10 Citrate C00158 TCA cycle CRC, RCC 10 Various (>5 diseases) Bile acids1 - Bile acid metabolism Bladder, RCC, Ovarian 9 Not assigned for group of metabolites Hypoxanthine C00262 Nucleotide/ nucleoside metabolism Breast, 9 Various (>5 diseases) Nasopharyngeal, Lymphoma Oleic acid C00712 Fatty acid 9 Hippurate C01586 Gut microbiota metabolite CRC, RCC 9 Various (>5 diseases) Succinate C00042 TCA cycle Breast, RCC 8 Severely malnourished children, lung cancer Arachidonic acid C00219 Fatty acid RCC 8 Hypertension, gestational diabetes Alanine C00041 Amino acid CRC 7 Various (>5 diseases) Lysine C00047 Amino acid 7 Aspartate C00049 Amino acid CRC 7 Cirrhosis, epilepsy, Alzheimer’s disease Asparagine C00152 Amino acid 7 Arabinose C00259 Sugar CRC 7 Ribose-5-phosphate 4 Metabolomics in cancer research: Supplementary data Metabolite KEGG ID Metabolic class, pathway or comment Cancer Reported Disease endpoints associated (only validated studies) Frequency with altered concentrations (HMDB) isomerase deficiency Kynurenine C00328 Tryptophan metabolism CRC 7 N/A Myristic acid C06424 Fatty acid CRC 7 N/A Uridine C00299 Nucleotide/ nucleoside metabolism CRC 7 Lesch-Nyhan syndrome, Canavan disease Galactose C00124 Sugar 6 Histidine C00135 Amino acid 6 Cholesterol C00187 Steroid metabolism 6 Creatinine C00791 Phosphorylation Breast 6 Chronic renal failure + various (>5 diseases) Stearic acid C01530 Fatty acid 6 Urea C00086 Urea cycle Breast, CRC 6 Cirrhosis, heart transplant Lysophosphoethanolamines1 - 5 Pyruvate C00022 Glycolysis CRC 5 Heart transplant, 2- methylglutaconic aciduria, diabetes type I Ornithine C00077 Urea cycle 5 Taurine C00245 Bile acid metabolism Breast 5 Various (>5 diseases) Isoleucine C00407 Amino acid 5 Phosphocholine C00588 PC metabolism 5 2-Hydroxybutyrate C05984 Fatty acid metabolism CRC 5 Pyruvate dehydrogenase deficiency Uracil C00106 Nucleotide/ nucleoside metabolism CRC, RCC 5 Various (>5 diseases) Gangliosides1 - Bladder, RCC 4 Not assigned for group of metabolites Heptadecanoic acid - Fatty acid Breast 4 N/A Oleamide - Fatty acid metabolism 4 5 Metabolomics in cancer research: Supplementary data Metabolite KEGG ID Metabolic class, pathway or comment Cancer Reported Disease endpoints associated (only validated studies) Frequency with altered concentrations (HMDB) Phosphate C00009 4 2-Oxoglutarate C00026 TCA cycle 4 Fructose C00095 Sugar RCC 4 Diabetes Beta-alanine C00099 Amino acid metabolism RCC 4 Dihydropyrimidine dehydrogenase deficiency, GABA transaminase deficiency, hyper-beta- alaninemia Aminoadipate C00956 Lysine metabolism 4 Ribose C00121 Sugar 4 Mannose C00159 Sugar 4 Inosine C00294 Nucleotide/ nucleoside metabolism 4 Pipecolic acid C00408 Lysine metabolism 4 Linoleic acid C01595 Fatty acid 4 1-Methyladenosine C02494 Nucleotide/ nucleoside metabolism 4 Hydroxybutyrate C05984 Propanoate metabolism / byproduct of 4 homocysteine methylation Nucleosides1 Nucleotide/ nucleoside metabolism 4 2,2-Dimethylguanosine - Nucleotide/ nucleoside metabolism 3 Tocopherol - Vitamin RCC 3 α-Toc.: cancer; γ-Toc.