Table 1.
A list of recent reports in which patients with gastroenterological cancer were subjected to metabolome analysis.
| Disease | Specimen | Upregulated Metabolites | Downregulated Metabolites | Analytical Method | Ref. |
|---|---|---|---|---|---|
| Oral cancer | Saliva | Lactate; n-Eicosanoate | Valine; GABA; Phenylalanine | UPLC-Q-TOF/MS | [20] |
| Research aim: To discover salivary metabolite biomarkers and to explore salivary metabolomics as a disease diagnostic tool | |||||
| Oral cancer | Saliva | Cadaverine; 2-Aminobutyrate; Alanine; Piperidine; Taurine; Piperideine; Pipecolate; Pyrroline hydroxycarboxylate; Betaine; Leucine + Isoleucine; Phenylalanine; Tyrosine; Histidine; Valine; Tryptophan; β-Alanine; Glutamate; Threonine; Serine; Glutamine; Choline; Carnitine | None | CE-TOF-MS | [21] |
| Research aim: To predict oral cancer susceptibility via saliva-based diagnostics based on metabolomics technology | |||||
| Oral cancer | Urine | Alanine; Valine; Serine; Tyrosine; Cystine | 6-Hydroxynicotinate; Hippurate | GC-QMS | [22] |
| Research aim: To establish a diagnostic tool for early stage oral squamous cell carcinoma and its differentiation from other oral conditions by the urinary metabolite profiling approach | |||||
| Oral cancer | Serum | Glycerate; Serine; Laurate; N-Acetyl-l-aspartate; Asparagine; Ornithine; Heptadecanate | None | GC-QMS | [23] |
| Research aim: To find metabolite biomarker candidates for detection of early stage oral squamous cell carcinoma | |||||
| Esophageal cancer | Mucosal tissue | l-Valine; Naphthalene; 1-Butanamine; Pyrimidine; Aminoquinoline; l-Tyrosine; Isoleucine; Purine; Serine; Phosphate; myo-Inositol; Arabinofuranoside; l-Asparagine; Tetradecanoate; l-Alanine; Hexadecanoate | l-Altrose; d-Galactofuranoside; Arabinose; Bisethane | GC-QMS | [24] |
| Research aim: To find tissue metabolomic biomarkers that are identifiable and diagnostically useful for esophageal cancer | |||||
| Esophageal cancer | Mucosal tissue | N-acetylaspartate; Glutamate; Valine; Leucine + Isoleucine; Tyrosine; Methionine; Phenylalanine; GABA; Phenylacetylglutamine; Glutamic acid γ-H; Unsaturated lipids; Short-chain fatty acids; Phosphocholine; Glycoproteins; Acetone; Malonate; Acetoacetate; Acetate; Trimethylamine; Formate; Uracil; Adenine in ATP/ADP and NAD/NADH; Acetyl hydrazine; Hippurate | Creatine; Glycine; Glutamine; 4-Hydroxyphenylpyruvate; Creatinine; Taurine; Aspartate; myo-Inositol; Cholesterol; Choline; Glucose; Ethanol; α-Ketoglutarate oxime; AMP; NAD | NMR | [25] |
| Research aim: To find the potential tissue metabolite biomarkers for clinical diagnosis for different stages of human esophageal cancer and new insights for the mechanism research | |||||
| Esophageal cancer | Tissue | Choline; Alanine; Glutamate | Creatinine; myo-Inositol; Taurine | NMR | [26] |
| Research aim: To establish the biochemical profiles of adjacent non-involved tissue and malignant esophageal tumor and to determine the metabolomic changes of tumors with different tumor differentiation for finding metabolomic indicators sensitive to tumor differentiation | |||||
| Esophageal cancer | Urine | Urea; Acetate; Pantothenate; 3-Hydroxyisovaleate; Acetone; Formate; 2-Hydroxyisobutyrate; Creatinine; Ethanolamine; 2-Aminobutyrate; Leucine; Succinate; Glutamine; Glucose; Glycine; Tryptophan; Trimethylamine-N-oxide; Valine; Lactate; Tyrosine | Dimethylamine; Alanine; Citrate | NMR | [27] |
| Research aim: To find urinary metabolite signatures that can clearly distinguish both Barrett’s esophagus and esophageal cancer from controls | |||||
| Esophageal cancer | Serum | Uridine | 1-Methyladenosine; N2,N2-Dimethylguaosine; N2-Methylguanosine; Cytidine | LC-QqQ/MS | [28] |
| Research aim: To investigate whether nucleosides can potentially serve as useful biomarkers to identify esophageal adenocarcinoma | |||||
| Esophageal cancer | Serum | Lactate; β-Hydroxybutyrate; Lysine; Glutamine; Citrate | Valine; Leucine + Isoleucine; Methionine; Tyrosine; Tryptophan; Myristate; Linoleate | LC-Q-TOF/MS
NMR |
[29] |
| Research aim: To identify the metabolite based biomarkers associated with the early stages of esophageal adenocarcinoma with the goal of improving prognostication | |||||
| Esophageal cancer | Serum | β-Hydroxybutyrate; Acetoacetate; Creatine; Creatinine; Lactate; Glutamate; Glutamine; Histine | LDL/VLDL; Unsaturated lipids; Acetate; α-Glucose; β-Glucose; Tyrosine | NMR | [30] |
| Research aim: To characterize the systemic metabolic disturbances underlying esophageal cancer and to identify possible early biomarkers for clinical prognosis | |||||
| Esophageal cancer | Serum | Lactate; Glycolate; Malonate; Fumarate; l-Serine; l-Aspartate; l-Glutamine | Pyruvate | GC-QMS | [31] |
| Research aim: To investigate the differences in serum metabolite profiles using a metabolomic approach and to search for sensitive and specific metabolomic biomarker candidates | |||||
| Esophageal cancer | Plasma | Phosphatidylinositol; Lithocholyltaurine; Phosphatidiate; L-Urobilinogen; 9'-Carboxy-γ-tocotrienol; PC; PE; Sphinganine 1-phosphate; Phosphatidylserine(16:0/14:0); LPC(22:2); Ganglioside GM2(d18:1/24:1(15Z)); Lithocholate 3-O-glucuronide; 12-Oxo-20-dihydroxy-leukotriene B4 | Desmosine; Isodesmosine; 5-β-Cyprinol sulfate | UPLC-TOF/MS | [32] |
| Research aim: To search for valuable markers including circulating endogenous metabolites associated with the risk of esophageal cancer | |||||
| Gastric cancer | Tissue | 2-Aminobutyrate; 3-Aminoisobutanoate; Valine; 2-Hydroxy-4-methyl-pentanoate; Isoleucine; Proline; Uracil; Threonine; Thymine; Dihydrouracil; Aspartate; Pyroglutamate; GABA; Cysteine; Glutamate; Dodecanoate; Asparagine; Putrescine; Cadaverine; Ascorbate; Gluconate; Xanthine; N-Acetyl glucosamine; Kynurenine; Inosine | Hydroxyacetate; 3,4-Dihydroxy-2(3H)-furanone; Nicotinamide; Glycerol phosphate; Tetradecanoate; Palmitelaidate; Palmitate; Linoleate; Stearate; Arachidonate; l-Palmitoyl-glycerol; Sucrose; Cholesterol | GC-TOF/MS | [33] |
| Research aim: To reveal the major metabolic alterations essential for the development of gastric cardia cancer and to discover a biomarker signature of gastric cardia cancer | |||||
| Gastric cancer | Urine | Arginine; Leucine; Valine; Isoleucine; Lactate | Methionine; Serine; Aspartate; Histidine; Succinate; Citrate; Malate | CE-MS | [34] |
| Research aim: To search for potential tumor markers of gastric cancer in patients’ urine samples | |||||
| Gastric cancer | Serum | 3-Hydroxypropionate; 3-Hydroxyisobutyrate | Pyruvate; Octanoate; Phosphate | GC-QMS | [31] |
| Research aim: To investigate the differences in serum metabolite profiles using a metabolomic approach and to search for sensitive and specific metabolomic biomarker candidates | |||||
| Gastric cancer | Serum | L-Valine; Sarcosine; Hexadecanenitrile | L-Glutamine; Hexanedioate; 9,12-Octadecadienoate; 9-Octadecenoate; trans-13-Octadecenoate; Nonahexacontanoate; Cholesta-3,5-diene; Cholesterol/Pentafluoropropionate; Cholesterol; Cholest-5-en-3-ol; Fumarate; 2-o-Mesyl arabinose; Benzeneacetonitrile; 2-Amino-4-hydroxy-pteridinone; 1,2,4-Benzenetricarboxylate | GC-QMS | [35] |
| Research aim: To explore the underlying metabolic mechanisms of gastric cancer and to identify biomarkers associated with morbidity | |||||
| Colorectal cancer | Mucosal tissue | Lactate; Phosphate; l-Glycine; 2-Hydroxy-3-methylvalerate; l-Proline; L-Phenylalanine; Palmitate; Margarate; Oleate; Stearate; Uridine; 11,14-Eicosadienoate; 11-Eicosenoate; 1-o-Heptadecylglycerol; 1-Monooleoylglycerol; Propyl octadecanoate; Cholesterol | Fumarate; Malate; d-Mannose; d-Galactose; d-Glucose; 1-Hexadecanol; Arachidonate | NMR
GC-QMS |
[36] |
| Research aim: To reveal that global metabolic profiling of colon mucosae can define metabolic signatures for not only discriminating malignant from normal mucosae but also distinguishing the anatomical and clinicopathological characteristics of colorectal cancer | |||||
| Colorectal cancer | Tissue | Glycine; l-Proline; l-Phenylalanine; l-Alanine; l-Leucine; l-Valine; l-Serine; l-Threonine; l-Isoleucine; Picolinate; l-Methionine; l-Aspartate; β-Alanine; Aminomalonate; 1-Methylhydantoin; Palmitate; Margarate; Oleate; Stearate; 11-Eicosenoate; Myristate; Pentadecanoate; Linolenate; Lignocerate; Phosphate; l-Arabinose; Lactate; Maleate; Pantothenate; Glycerol; 1-Monooleoylglycerol; Uracil; Uridine; Cholesterol | Arachidonate; d-Mannose; d-Galactose; d-Glucose; Fumarate; Malate; Oxalate; Succinate; Ribitol; Squalene | GC×GC-TOF/MS | [37] |
| Research aim: To investigate whether the metabotype associated with colorectal cancer is distinct from that of normal tissue and whether various biochemical processes are altered by pathogenesis of colorectal cancer | |||||
| Colorectal cancer | Urine | Lactate; Arginine; Leucine; Isoleucine; Valine | Histidine; Methionine; Aspartate; Serine; Succinate; Citrate; Malate | CE-IT/MS | [18] |
| Research aim: To investigate the metabolic profile of urine metabolites and to elucidate their clinical significance in patients with colorectal cancer including possibility as the biomarker candidates for early detection. | |||||
| Colorectal cancer | Urine | 5-Hydroxytryptophan; 5-Hydroxyindoleacetate; Tryptophan; Glutamate; Pyroglutamate; N-Acetyl-aspartate; p-Cresol; 2-Hydroxyhippurate; Phenylacetate; Phenylacetylglutamine; p-Hydroxyphenylacetate | Succinate; Isocitrate; Citrate; 3-Methylhistidine; Histidine | GC-QMS | [19] |
| Research aim: To demonstrate the potentials of this noninvasive urinary metabolomic strategy as a complementary diagnostic tool for colorectal cancer | |||||
| Colorectal cancer | Serum | None | FAs (C28H46O4, C28H48O4, C28H50O4) | FTICR-MS
LC-Q-TOF/MS NMR QqQ-MS |
[38] |
| Research aim: To discover putative metabolomic markers associated with colorectal cancer | |||||
| Colorectal cancer | Serum | Pyruvate; α-Hydroxybutyrate; Phosphate; Isoleucine; β-Alanine; meso-Erythritol; Aspartate; Pyroglutamate; Glutamate; p-Hydroxybenzoate; Arabinose; Asparagine; Xylitol; Ornithine; Citrulline; Glucuronate; Glucosamine; Palmitoleate; Inositol; Kynurenine; Cystamine; Cystine; Lactitol | Nonanoate; Creatinine; Ribulose; o-Phosphoethanolamine | GC-QMS | [39] |
| Research aim: To establish new screening methods for early diagnosis of colorectal cancer via metabolomics | |||||
| Colorectal cancer | Serum | Lactate; Glycolate; l-Alanine; 3-Hydroxypropionate; l-Proline; L-Methionine; Thioglycolate; l-Glutamate; l-Asparagine; l-Glutamine; Glucuronic lactone | None | GC-QMS | [31] |
| Research aim: To investigate the differences in serum metabolite profiles using a metabolomic approach and to search for sensitive and specific metabolomic biomarker candidates | |||||
| Colorectal cancer | Serum | LPC(16:0); LPC(18:2); LPC(18:1); LPC(18:0); LPC(20:4); LPC(22:6); PC(34:1); LPA(16:0); LPA(18:0); LPC(16:0) | Palmitic amide; Oleamide; Hexadecanedioate; Octadecanoate; Eicosatrienoate; Myristate | DI-FTICR-MS | [40] |
| Research aim: To discriminate colorectal cancer patients from controls by metabolomic biomarkers and to reveal the stage-related biomarkers for colorectal cancer and the changing trends of four lipid species in the colorectal cancer progression | |||||
| Hepatic cancer | Tissue | Arachidyl carnitine; Tetradecanal; Oleamide | β-Sitosterol; l-Phenylalanine; LPC(18:2); Glycerophosphocholine; LPE(18:3); Chenodeoxycholate glycine conjugate; LPC(22:6); Quinaldate; LPE(18:0); LPC(18:0); LPC(20:4) | LC-LTQ-Orbitrap-MS | [41] |
| Research aim: To select characteristic endogenous metabolites in hepatitis B virus-related hepatocellular carcinoma patients and to identify their molecular mechanism and potential clinical value | |||||
| Hepatic cancer | Urine | Octanedioate; Glycine; Tyrosine; Threonine; Butanedioate | Heptanedioate; Ethanedioate; Xylitol; Urea; Phosphate; Propanoate; Pyrimidine; Butanoate; Trihydroxypentanoate; Hypoxanthine; Arabinofuranose; Hydroxyproline dipeptide; Xylonate | GC-QMS | [42] |
| Research aim: To investigate the urinary metabolic difference between hepatocellular carcinoma patients and normal subjects and to find biomarkers for hepatocellular carcinoma | |||||
| Hepatic cancer | Serum | Cortisol; GCA; GCDCA; C16:1-CN; FAs (C16:1, C16:0, C18:2, C18:1, C18:0, C20:5, C20:4, C20:2, C22:6, C22:5) | Tryptophan; LPC(14:0); LPC(20:3); LPC(20:5); C10-CN; C10:1-CN; C8-CN; C6-CN | LC-Q-TOF/MS | [43] |
| Research aim: To study the related metabolic deregulations in hepatocellular carcinoma and chronic liver diseases and to discover the differential metabolites for distinguishing the different liver diseases | |||||
| Hepatic cancer | Plasma | LPC(24:0); Glycodeoxycholate; Deoxycholate 3-sulfate | LPC(14:0); LPC(16:0); LPC(18:0); LPC(18:1); LPC(18:2); LPC(18:3); LPC(20:4); FA(24:0); FA(24:1); LPC(20:2); LPC(20:3); LPC(20:5) | UPLC-QqQ/MSGC-QMS | [44] |
| Research aim: To evaluate the molecular changes in the plasma of hepatocellular carcinoma patients and to provide new insights into the pathobiology of the diseases | |||||
| Hepatic cancer | Feces | LPC(18:0); LPC(16:0) | Chenodeoxycholate dimeride; Urobilin; Urobilinogen; 7-Ketolithocholate | UPLC-Q-TOF/MS | [45] |
| Research aim: To find fecal metabolite biomarkers for distinguishing liver cirrhosis and hepatocellular carcinoma patients from healthy controls | |||||
| Pancreatic cancer | Saliva | Cadaverine; 2-Aminobutyrate; Alanine; Putrescine; Methylimidazole acetate; Trimethylamine; Piperidine; Leucine + Isoleucine; Phenylalanine; Tyrosine; Histidine; Proline; Lysine; Glycine; Ornithine; Burimamide; Ethanolamine; GABA; Aspartate; Valine; Tryptophan; β-Alanine; Glutamate; Threonine; Serine; Glutamine; Hypoxanthine; Choline; Carnitine | Taurine; Glycerophosphocholine | CE-TOF-MS | [21] |
| Research aim: To reveal the comprehensive salivary metabolic profiles of pancreatic cancer patients and healthy controls and to identify cancer-specific biomarkers with high discriminative ability | |||||
| Pancreatic cancer | Tissue | Taurine | Succinate; Malate; Uridine; Glutathione; UDP-N-Acetyl-d-glucosamine; NAD; UMP; AMP | UPLC-TOF/MS | [46] |
| Research aim: To investigate the differences in the metabolite profiles of normal and pancreas tumor tissue with a goal of developing prognostic biomarkers | |||||
| Pancreatic cancer | Serum | Lactate; Thiodiglycolate; 7-Hydroxyoctanoate; Asparagine; Aconitate; Homogentisate; N-Acetyl-tyrosine | Glycine; Urea, Octanoate; Glycerate; Decanoate; Laurate; Myristate; Palmitate; Urate; Margarate; Stearate | GC-QMS | [47] |
| Research aim: To evaluate the differences in the metabolomes between pancreatic cancer patients and healthy volunteers and to aid the discovery of novel biomarkers | |||||
| Pancreatic cancer | Serum | Arabinose; Ribulose | Valine; 2-Aminoethanol; n-Caprylate; Threonine; Nonanoate; Methionine; Creatinine; Asparagine; Glutamine; o-Phosphoethanolamine; Glycyl-Glycine; 1,5-Anhydro-d-glucitol; Lysine; Histidine; Tyrosine; Urate | GC-QMS | [48] |
| Research aim: To construct a diagnostic model for pancreatic cancer using serum metabolomics and to confirm its diagnostic performance | |||||
| Pancreatic cancer | Plasma | Arachidonate; Erythritol; Cholesterol; N-Methylalanine; Lysine; Deoxycholylglycine; Cholylglycine; LPC(16:0); Tauroursodeoxycholate; Taurocholate; LPC(18:2); PE(26:0); PC(34:2) | Glutamine; Hydrocinnamate; Phenylalanine; Tryptamine; Inosine | GC-TOF/MS
LC-IT/MS LC-LTQ-Orbitrap-MS |
[49] |
| Research aim: To seek novel metabolic biomarkers of pancreatic cancer | |||||
In this review, we searched for the articles, in which the evaluations of differences between cancer and control were performed by metabolomics using gas chromatography-mass spectrometry (GC-MS), liquid chromatography-mass spectrometry (LC-MS), capillary electrophoresis-mass spectrometry (CE-MS), Fourier transform ion cyclotron resonance (FTICR-MS) and nuclear magnetic resonance (NMR), via PubMed database and so on, and their articles were shown in Table 1. In Table 1, the instruments used for metabolomics were described to specify the analytical method, and the aim of each article was also stated. In Table 1, upregulated or downregulated metabolites in serum/plasma, saliva, feces or urine of the cancer patients compared with healthy controls were listed. Regarding tissues, upregulated or downregulated metabolites in tumor tissues compared with non-tumor (normal) tissues in cancer patients were shown. Table 1 shows the list of metabolites that were demonstrated to be significantly changed between cancer and control in each article. In some articles, many metabolites with the significant alterations between cancer and control were exerted. Regarding these articles, only metabolites that were determined as biomarker candidates based on each criterion was listed in Table 1.
Abbreviations: GABA, γ-Aminobutyrate; LPC, Lysophosphatidylcholine; PC, Phosphatidylcholine; LPA, Lysophosphatidate; LPE, Lysophosphatidylethanolamine; PE, Phosphatidylethanolamine; FA, Fatty acids; GCDCA, Glycochenodeoxycholate; GCA, Glycocholate; UDP, Uridine diphosphate; NAD, Nicotinamide adenine dinucleotide; UMP, Uridine monophosphate; AMP, Adenosine monophosphate; ATP, Adenosine triphosphate; CE-IT/MS, Capillary electrophoresis-ion-trap/mass spectrometry; CE-MS, Capillary electrophoresis-mass spectrometry; CE-TOF-MS, Capillary electrophoresis-time-of-flight mass spectrometry; DI-FTICR-MS, Direct infusion-Fourier transform ion cyclotron resonance-mass spectrometry; FTICR-MS, Fourier transform ion cyclotron resonance-mass spectrometry; GC×GC-TOF/MS, Two-dimensional gas chromatography-time-of-flight mass spectrometry; GC-QMS, Gas chromatography-quadrupole mass spectrometry; GC-TOF/MS, Gas chromatography-time-of-flight mass spectrometry; LC-IT/MS, Liquid chromatography-ion-trap/mass spectrometry; LC-LTQ-Orbitrap-MS, Liquid chromatography-linear ion trap quadrupole-Orbitrap-mass spectrometry; LC-QqQ/MS, Liquid chromatography-triple quadrupole/mass spectrometry; LC-Q-TOF/MS, Liquid chromatography-quadrupole-time-of-flight/mass spectrometry; NMR, nuclear magnetic resonance; QqQ-MS, Triple quadrupole-mass spectrometry; UPLC-QqQ/MS, Ultra performance liquid chromatography-triple quadrupole/mass spectrometry; UPLC-Q-TOF/MS, Ultra performance liquid chromatography-quadrupole-time-of-flight/mass spectrometry; UPLC-TOF/MS, Ultra performance liquid chromatography-time-of-flight/mass spectrometry.