Table 1.
Metabolomics studies focused on the analysis of biofluids to identify clinically relevant prostate cancer (PCa) biomarkers.
| Article | Sample | Experimental Approach | Research Aim | Sample Cohort | Main Findings | Validation Cohort |
|---|---|---|---|---|---|---|
| Clos-Garcia et al., 2018 [37] | Urine EVs | UHPLC-MS | Diagnosis | 31 × PCa; 14 × BPH | Statistically significant changes in 76 metabolites and 7 enzymes related to urea cycle, TCA cycle, and metabolism of steroid hormone biosynthesis, leukotriene, and prostaglandin, linoleate and purine, glycerophospholipid and tryptophan | No |
| Liang et al., 2017 [38] | Urine | FPLC-MS/MS | Diagnosis | 236 × PCa; 233 × HV | ↑ glycocholic acid; hippurate; chenodeoxycholic acid: PCa > HV ↓ taurocholic acid; 5-hydroxy-l-tryptophan: PCa < HV |
No |
| Gkotsos et al., 2017 [39] | Urine | UPLC-MS/MS | Diagnosis | 52 × PCa, 49 × HV | ↓ kynurenic acid: PCa < HV | No |
| Struck-Lewicka et al., 2015 [40] | Urine | HPLC-TOF-MS; GC-QqQ-MS | Diagnosis | 32 × PCa; 32 × HV | Statistically significant changes in 82 metabolites related to amino acid, organic acids, sphingolipids, fatty acids, and carbohydrates metabolism | No |
| Fernández-Peralbo et al., 2016 [41] | Urine | LC-QTOF-MS/MS | Diagnosis | 43 × PCa; 29 × HV | ↑ 7-methylguanine: PCa > HV ↓ Statistically significant changes in 27 metabolites related to amino acid metabolism: PCa < HV |
19 × PCa; 13 × HV |
| Puhka et al., 2017 [42] | Urine EVs; Plasma EVs | UPLC-MS/MS | Diagnosis | 3 × PCa pre-prostatectomy; 3 × PCa post-prostatectomy; 3 × HV | ↓ glucoronate; isobutyryl-L-carnitine; D-Ribose-5-phosphate: pre- < post-prostatectomy and HV | No |
| Fujita et al., 2017 [43] | Urine EVs | iTRAQ; LC-MS/MS | Diagnosis and prognosis | 12 × PCa (6 × HG PCa; 6 × LG PCa); 6 × HV | ↑ FABP5: PCa > HV ↑ FABP5; GRN; AMBP; CHMP4A; CHMP4C associated with higher GS |
18 × PCa (6 × HG; 12 × LG); 11 × HV |
| Perez-Rambla et al., 2017 [44] | Urine | 1H-NMR | Diagnosis | 64 × PCa; 51 × BPH | ↑ BCAAs; glutamate; pseudouridine: PCa > BPH ↓ glycine; dimethylglycine; fumarate; 4-imidazole-acetate: PCa < BPH |
No |
| Davalieva et al., 2015 [45] | Urine | 2D-DIGE-MS | Diagnosis | 8 × PCa; 16 × BPH | ↑ AMBP: PCa > BPH ↓ HP: PCa < BPH |
16 × PCa; 16 × BPH |
| Heger et al., 2015 [48] | Urine | 2D-DIGE; MALDI-TOF-MS | Diagnosis | 15 × HG PCa; 15 × LG PCa | ↑ CDK6; M2BP; LDHC: HG PCa > LG PCa | No |
| Kumar et al., 2016 [46] | Serum | 1H-NMR | Diagnosis | 75 × PCa; 70 × BPH; 65 x HV |
↑ alanine; sarcosine; creatine; creatinine: PCa > BPH and HV ↑ pyruvate; 3-methylhistidine; xanthine; hypoxanthine: BPH and PCa > HV ↓ glycine: PCa < HV ↓ citrate: PCa < BPH and HV |
No |
| Kumar et al., 2015 [47] | Serum | 1H-NMR | Diagnosis and prognosis | 21 × HG PCa; 28 × LG PCa; 22 × HV | ↑ alanine; sarcosine: LG PCa > HG PCa and HV ↑ pyruvate: LG PCa and HG PCa > HV ↓ glycine: LG PCa and HG PCa < HV |
9 × HG PCa; 12 × LG PCa; 12 × HV |
| Giskeødegård et al., 2015 [49] | Plasma/Serum | 1H-NMR; UPLC-MS/MS; GC-MS | Diagnosis | 29 × PCa; 21 × BPH | ↑ decanoylcarnitine (c10); tetradecenoylcarnitine (c14:1); octanoyl-carnitine (c8); dimethylsulfone; phenylalanine; lysine: PCa > BPH ↓ phosphatidylcholine diacyl (c34:4); lipid -(CH2)n-CH2-CH2-CO: PCa < BPH |
No |
| Zhao et al., 2017 [50] | Plasma | UPLC-MS/MS | Diagnosis | 32 × PCa; 32 × HV | Statistically significant changes in 19 metabolites related to amino acid, nucleotide, butanoate and propionate metabolism | No |
| Lin et al., 2017 [51] |
Plasma | LC-MS/MS | Prognosis | 96 × CRPC | ↑ ceramide d18:1/24:1; sphingomyelin d18:2/16:0; phosphatidylcholine 16:0/16:0 correlated with shorter overall survival | 63 × CRPC |
| Mondul et al., 2015 [52] | Serum | UHPLC-MS; GC-MS | PCa risk Prognosis |
100 × HG PCa; 100 × LG PCa; 200 × HV |
Statistically significant changes in 22 metabolites related to lipid and amino acid metabolism associated with overall PCa risk Statistically significant changes in 14 metabolites related to TCA cycle and lipid metabolism associated with HG PCa Statistically significant changes in 34 metabolites related to lipid, amino acid and nucleotide metabolism associated with LG PCa |
No |
| Kühn et al., 2016 [53] | Plasma | LC-MS/MS; FIA-MS/MS |
PCa risk | 310 × PCa; 774 × HV | ↑ Phosphatidylcholine (PC) associated with higher risk of PCa ↑ lysoPC associated with lower risk of PCa |
No |
| Schmidt et al., 2017 [54] | Plasma | QqQ-MS | PCa risk Prognosis |
1077 × PCa; 1077 × HV 208 × advanced PCa; 456 × localized PCa |
Statistically significant changes in 14 metabolites related to lipid and amino acid metabolism associated with overall PCa risk 12 glycerophospholipids inversely associated with risk of advanced PCa |
No No |
| Huang et al., 2017 [55] | Serum | UHPLC-MS; GC-MS | PCa risk | 71 × PCa T2 stage; 51 × PCa T3 stage; 15 × PCa T4 stage; 200 × HV | Statistically significant changes in 8 metabolites related to histidine and uridine metabolism associated with PCa T2 risk. Statistically significant changes in 12 metabolites related to fatty acid and primary bile acid metabolism associated with PCa T3 risk Statistically significant changes in 16 metabolites related to TCA, BCAA secondary bile acid, sex steroids and histamine metabolism associated with PCa T4 risk. |
No |
| Andras et al., 2017 [56] | Serum | HPLC-ESI-QTOF-MS | Prediction | 59 × patients with high PSA levels | 6 metabolites involved in lipid, purine and tryptophan metabolism predictive for prostate biopsy outcome | 31 × patients with high PSA levels |
| Kline et al., 2006 [57] | Seminal fluid; Prostatic secretion | 1H-NMR | Diagnosis | 28 × PCa; 33 × HV | ↓ citrate: PCa < HV | No |
| Etheridge et al., 2018 [58] | Seminal fluid | ELISA | Diagnosis | 28 × PCa; 15 × HV | ↑ AMACR: PCa > HV |
No |
| Serkova et al., 2008 [59] | Prostatic secretion | 1H-NMR | Prediction PCa risk |
52 × PCa; 26 × HV | ↓ citrate; myo-inositol; spermine shown highly predictive of PCa and inversely associated with PCa risk | No |
| Averna et al., 2005 [60] | Seminal fluid | 1H-NMR | Diagnosis | 3 × PCa; 1 × BPH; 4 × HV | ↓ citrate: PCa < BPH | No |
| Roberts et al., 2017 [61] | Seminal fluid | 1H-NMR | Prediction | 98 × PCa; 53 × HV | Statistically significant changes in choline, valine and leucine, | No |
1H-NMR: Proton nuclear magnetic resonance spectroscopy; 2D-DIGE-MS: Two dimensional–difference gel electrophoresis–mass spectrometry; BCAA: Branched-chain amino acids; BPH: Benign Prostatic Hyperplasia; CRPC: Metastatic castration-resistant prostate cancer; ELISA: Enzyme-linked immunosorbent assay; EV: Extracellular vesicles; FIA-MS/MS: Flow injection analysis–tandem mass spectrometry; FPLC-MS: Fast ultra-high performance liquid chromatography–mass spectrometry; GC-MS: Gas chromatography–mass spectrometry; GC-QqQ-MS: Gas chromatography–triple quadrupole–mass spectrometry; HG: High-grade (GS ≥ 8); HPLC-ESI-QTOF-MS: High performance liquid chromatography–electrospray ionization–quadrupole time of flight–mass spectrometry; HPLC-TOF-MS: High performance liquid chromatography–time of flight–mass spectrometry; HV: Healthy Volunteers; iTRAQ: Isobaric tag for relative and absolute quantification; LC-MS: Liquid chromatography–mass spectrometry; LC-MS/MS: Liquid chromatography–tandem mass spectrometry; LG: Low-grade (GS ≤ 7); MALDI-TOF-MS: Matrix-assisted laser desorption ionization–time of flight–mass spectrometry; PCa: Prostate Cancer; PM: prostatic massage; QqQ-MS: Triple quadrupole–mass spectrometry; T: Stage; TCA: Tricarboxylic acid; UHPLC-MS: Ultra high performance liquid chromatography–mass spectrometry; UPLC-MS/MS: Ultra performance liquid chromatography–tandem mass spectrometry.