TABLE 1.
Metabolites in biofluid samples of cancer and non-cancer groups.
| Year | Sample types | Tumor types | Patients/animal models | Method | Discriminant metabolites or findings | Related metabolic pathways | Ref |
| 2016 | plasma | Papillary thyroid microcarcinoma | patients with cancer (n = 26) from healthy controls (n = 17) | NMR | Elevated levels of glucose, mannose, pyruvate and 3-hydroxybutyrate in plasma, are involved in the metabolic alterations in papillary thyroid microcarcinoma | Glycolysis, amino acid | Lu et al. (2016) |
| 2016 | plasma | Lung and liver cancer | lung (n = 50) and liver cancer patients (n = 50) | LC-MS | two values was discovered to identify lung and liver cancer, which were the product of the plasma concentration of putrescine and spermidine; and the ratio of the urine concentration of S-adenosyl-l-methionine and N-acetylspermidine | The pathways of polyamines metabolome | Xu et al. (2016) |
| 2020 | plasma | Pancreatic cancer | patients with pancreatic cancer (n = 60) from healthy controls (n = 60) | LC-MS | The top 10 ranked differential metabolites were precisely aligned as glycocholic acid, agmatine, melatonin, beta-sitosterol, sphinganine, hypoxanthine, spermidine, hippuric acid, creatine and inosine.new metabolite biomarkers in plasma (creatine, inosine, beta-sitosterol, sphinganine and glycocholic acid) can be used to readily diagnose pancreatic cancer in a clinical setting | purine metabolism, glycine and serine metabolism, arginine and proline metabolism, steroid biosynthesis, sphingolipid metabolism and bile metabolism | Luo et al. (2020) |
| 2019 | plasma | Pancreatic cancer | patients with pancreatic cancer (n = 22) from healthy controls (n = 40) | LC-MS | About 270 lipids belonging to 20 lipid species were found significantly dysregulated. LysoPC 22:0, PC (P-14:0/22:2) and PE (16:0/18:1) are all associated with tumor stage, CA19-9, CA242 and tumor diameter. What’s more, PE (16:0/18:1) is also found to be significantly correlated with the patient’s overall survival | lipids | Tao et al. (2019) |
| 2014 | plasma | Oral squamous cell carcinoma | Patients with locally advanced OSCC(n = 105) | GC-MS | Chemotherapy leads to up-regulation of fatty acids, steroids, and antioxidant substances. Lactate, glucose, glutamate, aspartate, leucine, and glycerol are associated with efficacy of induction chemotherapy. Lactate, glutamate, and aspartate can precisely predict the suitability and efficacy of induction chemotherapy | Glycolysis, amino acid, fatty acid | Ye et al. (2014) |
| 2019 | plasma | Breast cancer | 1,624 first primary incident invasive breast cancer cases and 1,624 matched controls | LC-MS | There were significant differences in lysoPCs in breast cancer patients. LysoPC aaC18:0 was negatively associated with the risk of breast cancer, while higher concentrations of phosphatidylcholine PC ae C30:0 were associated with an increased risk of breast cancer | lysoPCs | His et al. (2019) |
| 2018 | plasma | Pancreatic cancer | pancreatic ductal adenocarcinoma (n = 271), chronic pancreatitis (n = 282), liver cirrhosis (n = 100) or healthy as well as non-pancreatic disease controls (n = 261) | GC-MS | Proline, Sphingomyelin (d18:2, C17:0), Phosphatidylcholine, Isocitrate (C18:0, C22:6), Sphinganine-1-phosphate (d18:0), Histidine, Pyruvate, Ceramide (d18:1, C24:0), Sphingomyelin (d17:1, C18:0) and CA19-9 formed a biomarker signature. The biomarker signature could be identified as a differential diagnosis between pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis (CP) | complex lipids, fatty acids and related metabolites | Mayerle et al. (2018) |
| 2017 | Urine | Prostate cancer | 64 prostate cancer patients and 51 individuals diagnosed with benign prostate hyperplasia | NMR | Branchedchain amino acids, glutamate, pseudouridine, glycine, P = 0.015; dimethylglycine, fumarate and 4-imidazole- acetate were able to distinguish between prostate cancer and benign prostate hyperplasia (BPH) | TCA cycle of glucose metabolism | Pérez-Rambla et al. (2017) |
| 2012 | Urine | Kidney cancer | (Group A: 29 cancer patients, 33 controls; Group B: 6 cancers,6 controls) | GC-MS | Results showed differential urinary concentrations of several acylcarnitines as a function of both cancer status and kidney cancer grade, with most acylcarnitines being increased in the urine of cancer patients and in those patients with high cancer grades | acylcarnitines | Ganti et al. (2012) |
| 2011 | Urine | Bladder cancer | 27 bladder cancer (BC) patients and 32 healthy controls | LC-MS | Cancer patients have elevated levels of acetyl carnitine and adipate in their urine. Carnitine C9:1 and component I, were combined as a biomarker pattern | Fatty acid and carnitine metabolism | Huang et al. (2011) |
| 2020 | Urine | Breast cancer | patients with breast cancer (n = 56) and benign breast tumors (n = 22), as well as from healthy females (n = 20) | GC-MS | 1-methyl adenosine (1-MA), 1-methylguanosine (1-MG) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels were significantly elevated in the early stages of breast cancer, but no significant differences were observed between the benign tumor group and the healthy group | nucleoside metabolomes | Omran et al. (2020) |
| 2013 | Urine | Ovarian cancer | 40 preoperative epithelial ovarian cancer (EOC) patients, 62 benign ovarian tumor (BOT) patients, and 54 healthy controls | LC-MS | The concentrations of some urinary metabolites of 18 postoperative EOC patients among the 40 EOC patients changed significantly compared with those of their preoperative condition, and four of them suggested recovery tendency toward normal level after surgical operation, including N4-acetylcytidine, pseudouridine, urate-3-ribonucleoside, and succinic acid | nucleotide metabolism, histidine metabolism, tryptophan metabolism, mucin metabolism | Zhang et al. (2013) |
| 2019 | Urine | Lung cancer | lung cancer (n = 32) and healthy controls (n = 29) | GC–MS | Six metabolites were altered in urine (l-glycine, phosphoric acid, isocitric acid, inositol, palmitic acid and stearic acid) and four metabolites (l-glycine, phosphoric acid, isocitric acid and inositol) were decreased from patients with cancer, indicating a strong, unified marker of lung cancer pathology | Fatty acid and glucose metabolism | Callejón-Leblic et al. (2019) |
| 2010 | Saliva | Oral, breast and pancreatic cancer | 69 oral, 18 pancreatic and 30 breast cancer patients, 11 periodontal disease patients and 87 healthy controls | CE-TOFMS | They identified 57 principal metabolites that can be used to accurately predict the probability of being affected by each individual disease. Patients with oral cancer had significantly higher levels of salivary polyamines compared to the control group, and taurine and piperidin were identified as oral cancer-specific metabolites, providing promising markers for oral cancer screening | Polyamines and amino acid metabolism | Soini et al. (2010) |
| 2016 | Saliva | Oral cancer | patients with oral cancer (n = 24) and healthy controls (n = 44) | CE-TOFMS | In total, 85 metabolites in tumor and 45 metabolites in saliva were identified to be significantly different between oral cancer and controls, and the combination of S-adenosylmethionine and pipecolate can discriminate oral cancers from controls | metabolites in the urea cycle and one carbon cycle | Ishikawa et al. (2016) |
| 2017 | Saliva | Oral squamous cell carcinoma | 22 patients with oral squamous cell carcinoma (OSCC) and 21 healthy controls | CE-TOFMS | A total of 25 metabolites were revealed as potential markers to discriminate between patients with OSCC and healthy controls | Choline and metabolites of the BCAA cycle | Ohshima et al. (2017) |
| 2019 | Saliva | Breast cancer | 101 patients with invasive carcinoma of the breast, 23 patients with ductal carcinoma in situ, and 42 healthy controls | LC-MS | The levels of polyamines in the saliva of breast cancer patients were significantly increased. In addition, polyamines and their acetylated forms were elevated invasive carcinoma of the breast only | Polyamine metabolism | Murata et al. (2019) |
| 2018 | Saliva | Pancreatic cancer | patients with PC (n = 39), those with chronic pancreatitis (CP, n = 14), and controls (C, n = 26) | CE-TOFMS | Polyamines, such as spermine, N₁-acetylspermidine, and N₁-acetylspermine, showed a significant difference between patients with PC and those with C, and the combination of four metabolites including N₁-acetylspermidine showed high accuracy in discriminating PC from the other two groups | Polyamine metabolism | Asai et al. (2018) |
| 2012 | CSF | Malignant gliomas | 10 patients presenting malignant gliomas and seven control patients that did not present malignancy | LC-MS | One subtype contained metabolites rich in citric acid cycle components that distinguished the metabolic characteristics of patients with malignant glioma from those in the control group. Newly diagnosed patients were classified into different subtypes and showed low levels of metabolites involved in tryptophan metabolism, which may indicate a loss of inflammatory features | Metabolites from the citric acid cycle, gluconeogenesis, and pyrimidine metabolism, urea cycle | Locasale et al. (2012) |
| 2013 | CSF | Glioma | 32 patients with histologically confirmed | GC–MS | The citric and isocitric acid levels were significantly higher in the glioblastoma (GBM) samples than in the grades I-II and grade III glioma samples. In addition, the lactic and 2-aminopimelic acid levels were relatively higher in the GBM samples than in the grades I-II glioma samples. The CSF levels of the citric, isocitric, and lactic acids were significantly higher in grade I-III gliomas with mutant isocitrate dehydrogenase (IDH) than in those with wild-type IDH. | Metabolites from the aerobic glycolysis | Nakamizo et al. (2013) |
| 2020 | CSF | Medullo-blastoma (MB) | 8 patients diagnosed with recurrent MB and 7 healthy controls | LC-MS | The up-regulation of tryptophan, methionine, serine and lysine, which have all been described to be induced upon hypoxia in CSF. While cyclooxygenase products were hardly detectable, the epoxygenase product and beta-oxidation promoting lipid hormone 12,13-DiHOME was found to be strongly up-regulated | Lipid and amino acid metabolism | Reichl et al. (2020) |
| 2020 | CSF | different types of brain tumors | A cohort of 163 histologically-proven patients with brain disorders | LC-MS | A total of 508 ion features were detected by the LC-Q/TOF-MS analysis, of which 27 metabolites were selected as diagnostic markers to discriminate different brain tumor types | Amino acids and citrate metabolism | Wang et al. (2020) |
NMR, nuclear magnetic resonance; GC-MS, gas chromatography-mass spectrometry; LC-MS, liquid chromatography-mass spectrometry; CE-TOFMS, capillary electrophoresis time-of-flight mass spectrometry; CSF, cerebrospinal fluid.