Table 2.
List of VOCs significantly altered in PCa group compared to controls
| Chemical name (IUPAC) or common name | p-value | Variation ± uncertainty (%) | Effect size ± ESSE | AUC | Spec. | Sens. | HMDB29 | Matrices | Potential biochemical pathway |
|---|---|---|---|---|---|---|---|---|---|
| Aldehydes | |||||||||
| Hexanal L1 | 0.0313 | ↓ 14.62 ± 6.77 | ↓ 0.53 ± 0.45 | 0.641 | 0.76 | 0.51 | HMDB0005994 | Blood; Cerebrospinal fluid; Feces; Saliva; Urine29 | Steroid hormone biosynthesis20 |
| 3,4-Dimethylcyclohex-3-ene-1-carbaldehyde L1 | 0.0004B | ↓ 24.09 ± 8.68 | ↓ 0.71 ± 0.46 | 0.730 | 0.84 | 0.61 | NA | – | – |
| 2,5-Dimethylbenzaldehyde L1 | <0.0001B | ↑ 49.36 ± 9.90 | ↑ 0.91 ± 0.47 | 0.786 | 0.87 | 0.64 | HMDB0032014 | – | Alcohols and fatty acids metabolism40,48 |
| Ketones | |||||||||
| Hexan-2-one L1(2-Hexanone) | 0.0194 | ↓ 23.42 ± 10.77 | ↓ 0.56 ± 0.45 | 0.656 | 0.77 | 0.53 | HMDB0005842 | Urine; Feces29 | Fatty acid metabolism41 |
| 2-Methylcyclopentan-1-one L1 | 0.0129 | ↓ 31.26 ± 12.85 | ↓ 0.65 ± 0.46 | 0.662 | 0.78 | 0.55 | NA | – | Fatty acid metabolism41 |
| 4-Methylhexan-3-one L2 | 0.0022 | ↓ 16.49 ± 6.17 | ↓ 0.66 ± 0.46 | 0.701 | 0.82 | 0.59 | NA | – | Fatty acid metabolism41 |
| 5-Methylheptan-2-one L1 | 0.0073 | ↓ 21.40 ± 11.34 | ↓ 0.48 ± 0.45 | 0.677 | 0.80 | 0.51 | NA | Cell lines40 | Fatty acid metabolism41 |
| 4,6-Dimethylheptan-2-one L2 | 0.0174 | ↓ 17.04 ± 6.67 | ↓ 0.63 ± 0.46 | 0.658 | 0.76 | 0.55 | NA | – | Fatty acid metabolism41 |
| 2-Hydroxy-2-methyl-1-phenylpropan-1-one L1 | 0.0123 | ↓ 11.90 ± 4.03 | ↓ 0.71 ± 0.46 | 0.662 | 0.78 | 0.55 | NA | – | – |
| Alcohols | |||||||||
| 2,6-Dimethyl-6-hepten-2-ol L1 | 0.0002B | ↓ 36.42 ± 12.89 | ↓ 0.78 ± 0.46 | 0.748 | 0.84 | 0.63 | NA | – | Lipid metabolism40 |
| 1-Methyl-4-propan-2-ylcyclohex-2-en-1-ol L2 | 0.0026 | ↓ 13.49 ± 5.75 | ↓ 0.57 ± 0.45 | 0.698 | 0.81 | 0.57 | NA | – | Lipid metabolism40 |
| Monoterpene alcohols | |||||||||
| 3,7-Dimethylocta-1,6-dien-3-ol (Linalool)L1 | 0.0355 | ↓ 28.00 ± 13.53 | ↓ 0.55 ± 0.45 | 0.635 | 0.75 | 0.51 | HMDB0036100 | Feces29 | Lipid metabolism29 |
| 4-Methyl-1-propan-2-ylcyclohex-3-en-1-ol L1 (Terpinen-4-ol) | <0.0001B | ↓ 28.84 ± 8.35 | ↓ 0.91 ± 0.47 | 0.766 | 0.87 | 0.65 | HMDB0035833 | Feces; Cell lines29,40 | Lipid metabolism29 |
| Alkenes | |||||||||
| 4-Methyldec-1-ene L2 | 0.0321 | ↓ 18.31 ± 9.75 | ↓ 0.47 ± 0.45 | 0.635 | 0.75 | 0.52 | NA | – | |
| Cycloalkenes | |||||||||
| 2,2,7,7-Tetramethyltricyclo[6.2.1.0¹,6]undeca-3,5,9-triene (4,5,9,10-dehydroisolongifolene) L2 | 0.0379 | ↓ 15.98 ± 8.18 | ↓ 0.48 ± .045 | 0.634 | 0.76 | 0.50 | HMDB0059829 | Saliva29 | Steroid metabolism49 |
| Terpenes | |||||||||
| 3,7,7-Trimethylbicyclo[4.1.0] hept-3-ene (3-Carene) L1 | 0.0108 | ↓ 16.72 ± 6.46 | ↓ 0.64 ± 0.46 | 0.672 | 0.78 | 0.54 | HMDB0035619 | Feces29 | Lipid metabolism29 |
| 3-Methyl-6-(propan-2-ylidene)cyclohex-1-ene (Isoterpinolene) L2 | 0.0062 | ↓ 18.79 ± 8.17 | ↓ 0.58 ± 0.45 | 0.676 | 0.79 | 0.56 | HMDB0061938 | Saliva29 | Lipid metabolism29 |
| Others | |||||||||
| 2,2,2,8a-Tetramethyl-3,4,4a,5,6,8a-hexahydro-2H-chromene (Dihydroedulan IA) L2 | 0.0251 | ↓ 12.58 ± 5.46 | ↓ 0.56 ± 0.45 | 0.629 | 0.77 | 0.52 | NA | – | – |
| 5-Methyl-2-(propan-2-yl)cyclohexyl acetate L1 (Menthyl acetate) | 0.0139 | ↓ 12.89 ± 5.09 | ↓ 0.61 ± 0.45 | 0.662 | 0.77 | 0.54 | HMDB0041264 | – | Lipid metabolism29 |
| 2,6,6,10-Tetramethyl-1-oxaspiro[4.5]dec-9-ene (Theaspirane) L1 | 0.0096 | ↓ 13.36 ± 5.23 | ↓ 0.62 ± 0.45 | 0.668 | 0.78 | 0.55 | HMDB0036823 | Urine29 | Energetic metabolism; cell signalling; membrane stabilisation29 |
| Unidentified VOCs | |||||||||
| Unknown 1 L4 | 0.0137 | ↓ 12.70 ± 6.38 | ↓ 0.48 ± 0.45 | 0.661 | 0.77 | 0.53 | NA | – | – |
| Unknown 2 L4 | <0.0001B | ↓ 49.99 ± 17.13 | ↓ 0.88 ± 0.47 | 0.822 | 0.92 | 0.73 | NA | – | – |
| Unknown 3 L4 | 0.0006B | ↓ 23.54 ± 8.13 | ↓ 0.74 ± 0.46 | 0.727 | 0.84 | 0.62 | NA | – | – |
| Unknown 4 L4 | <0.0001B | ↓ 55.31 ± 13.34 | ↓ 1.30 ± 0.49 | 0.883 | 0.95 | 0.80 | NA | – | – |
| Unknown 5 L4 | 0.0031 | ↓ 14.50 ± 6.14 | ↓ 0.58 ± 0.45 | 0.695 | 0.81 | 0.58 | NA | – | – |
| Unknown 6 L4 | <0.0001B | ↓ 71.24 ± 10.61 | ↓ 1.12 ± 0.48 | 0.768 | 0.86 | 0.66 | NA | – | – |
| Unknown 7 L4 | 0.0093 | ↓ 15.01 ± 6.08 | ↓ 0.61 ± 0.45 | 0.665 | 0.77 | 0.54 | NA | – | – |
| Unknown 8 L4 | 0.0056 | ↓ 16.23 ± 7.55 | ↓ 0.53 ± 0.45 | 0.684 | 0.81 | 0.60 | NA | – | – |
| Unknown 9 L4 | <0.0001B | ↓ 16.12 ± 6.57 | ↓ 0.60 ± 0.45 | 0.808 | 0.90 | 0.70 | NA | – | – |
| Unknown 10 L4 | 0.0205 | ↓ 16.39 ± 7.42 | ↓ 0.55 ± 0.45 | 0.659 | 0.76 | 0.54 | NA | – | – |
| Unknown 11 L4 | 0.0043 | ↓ 21.05 ± 7.98 | ↓ 0.69 ± 0.46 | 0.677 | 0.78 | 0.55 | NA | – | – |
The statistical significance (p-values), percentage of variation, effect size (ES), standard error (ESSE), AUC, specificity (spec.) and sensitivity (sens.) are represented for each VOC, as well as the HMDB (human metabolome database) code (when available), the matrices where the compound was previously found and the potential biochemical pathways where the compound participates
NA not available
L1Identified metabolites (GC-MS analysis of the metabolite of interest and a chemical reference standard of suspected structural equivalence, with all analyses performed under identical analytical conditions within the same laboratory)54
L2Putatively annotated compounds (spectral (MS) similarity with NIST database), when standards were not commercially available54
L4Unidentified54
BAlterations remaining significant after Bonferroni correction, with cut-off p-value of 7.69 × 10−4 (0.05 divided by 65 analysed VOCs)