Updates and Original Case Studies Focused on the NMR-Linked Metabolomics Analysis of Human Oral Fluids Part II: Applications to the Diagnosis and Prognostic Monitoring of Oral and Systemic Cancers
Abstract
:1. Introduction
1.1. Appraisal of Benefits Offered by the 1H NMR Analysis of Human Saliva
Assignment Number/Code | Chemical Shift (δ/ppm) | Multiplicity | Assignment |
---|---|---|---|
1 | 0.92 | t | n-Butyrate-CH3 |
2 | 0.94 | broad | Protein BCAA side-chain-CH3 |
3 | 0.96 | t | Leucine-CH3 |
4 | 0.97 | d | Valine-CH3 |
5 | 1.02 | d | Valine-CH3 |
6 | 1.06 | t | Propioniate-CH3 |
7 | 1.20 | t | Ethanol-CH3 |
8 | 1.13 | d | iso-Butyrate-CH3 |
9 | 1.33 | d | Lactate-CH3 |
10 | 1.48 | d | Alanine-CH3 |
11 | 1.57 | tq | n-Butyrate-β-CH2 |
12 | 1.65 | m | 5-Aminovalerate-CH2′s |
13 | 1.80, 2.028 | 2 x s | Acetate-CH3 13C satellites |
14 | 1.87 | s | Thymine-CH3 |
15 | 1.92 | s | Acetate-CH3 |
16 | 1.95–2.10 | broad/sharp s | Broad: Glycoprotein -NHCOCH3/Sharp: Free Aminosugar- and N-Acetyl-amino acid-NHCOCH3 |
GlycA | 2.040 | s | GlycA APP N-Acetylglucosamine residues |
Nan-CH3 | 2.06 | s | Free N-Acetylneuraminate |
Met | 2.13 | s | Methionine-S(CH3)3 |
17 | 2.17 | q | Propioniate-CH2/n-Butyrate-α-CH2 |
18 | 2.23 | t | 5-Aminovalerate-CH2-CO2− |
Glu | 2.36 | m | Glutamate--β-CH2 |
19 | 2.38 | s | Pyruvate-CH3 |
20 | 2.405 | s | Succinate-CH2′s |
21 | 2.39 | m | Isobutyrate-CH |
22 | 2.59 | s | Methylamine H2NCH3 |
23 | 2.75 | s/m | DimethylamineH2N(CH3) /Methionine-CH2 |
24 | 2.95 | s | Trimethylamine N(CH3)3 |
25 | 3.04 | t | 5-Aminovalerate-5-CH2/Lysine-ε-CH2 |
DS | 3.145 | s | Dimethylsulphone-OS(CH3)2 |
26 | 3.21 | s | Choline-N(CH3)3+ |
27 | 3.24 | s | Betaine-N(CH3)3 |
28 | 3.25 | t | Taurine-CH2NH3+ |
29 | 3.38 | s | Methanol-CH3 |
30 | 3.43 | t | Taurine-CH2SO3− |
31 | 3.46 | d | cis-Aconitate-CH2 |
32 | 3.54 | dd | Glycerol-CH2OH |
33 | 3.56 | s | Glycine-CH2 |
34 | 3.66 | q/m | Ethanol-CH2/Glutamate-α-CH |
35 | 3.72 | m | Leucine-α-CH |
Glyc | 3.92 | s | Glycolate-CH2 |
Cr | 3.95 | s | Creatine-N(CH3) |
Nan | 4.02 | m | N-Acetylneuraminate-C4H |
36 | 4.13 | q | Lactate-CH |
37 | 6.88 | d | Tyrosine-Aromatic ring protons |
2-HPA | 6.93 | m | 2-Hydroxyphenylacetate-Aromatic ring proton |
38 | 7.06 | s | Histidine-Imidazole ring protons |
39 | 7.20 | d | Tyrosine-Aromatic ring protons |
40 | 7.32 | m | Phenylalanine-Aromatic ring proton |
41 | 7.36 | m | Phenylalanine-Aromatic ring proton |
42 | 7.42 | m | Phenylalanine-Aromatic ring proton |
43 | 7.65 | s | Guanine-CH= |
44 | 7.78 | s | Histidine-Imidazole ring protons |
45 | 8.05 | broad | * Protein aromatic amino acid residue(s) |
46 | 8.45 | s | Formate-CH |
47 | 9.57 | ** s(t) | Unassigned saturated aldehyde-CHO function |
1.2. 19F NMR Analysis of Human Saliva, Oral Biopsies and Tap Water
1.3. Importance of Metabolomics Investigations in Clinical Epidemiology
2. Metabolic Pathways That Sustain Cancer Cell Survival and Proliferation
3. Overview of the Metabolomics Screening of Saliva Specimens for Differential Groups of Cancer Conditions, including Selected Systematic Reviews Conducted: Applications to Diagnosis, Prognostic Severity Monitoring and Metabolic Pathway Dysregulations
4. Oral Cancers
4.1. Oral Squamous Cell Carcinoma
5. Extra-Oral (Systemic) Cancers
5.1. Head and Neck Squamous Cell Carcinoma
5.2. Lung Cancer
5.3. Breast Cancer
5.4. Pancreatic Cancer
5.5. Prostate Cancer
5.6. Colon Cancer
6. Oral Mucositis as a Response to Radiation Therapy
7. Case Study: An 1H NMR Evaluation of Acute-Phase Glycoproteins in WMSS Samples and Their Possible Applications as Biomarkers for Cancers and Inflammatory Disorders: Potential Interferences from 13C Satellites, Low-Molecular-Mass Biomolecules and Salivary Hyaluronate
8. Clinical Implications of the 1H NMR-Based Metabolomics Analysis of Human Saliva for Cancer Detection and Monitoring
9. Routes to Therapeutic Options and Drug Discovery
9.1. Recognition of Drug Targets
9.2. Drug Discovery Programmes
9.3. Potential Facilitation of Decisions to Be Made on Drug Treatments in Oncology (Untargeted or Targeted) with Available Metabolomics Datasets
10. Limitations of NMR-Based Metabolomics Investigations of Human Saliva for Cancer Diagnosis and Its Prognostic Monitoring
11. Key Concluding Remarks and Future Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Metabolite | Blood a | Saliva a |
---|---|---|
‘Free’ N-Acetylneuraminate | 0.6–2.0 μmol./L | 12.5–41.0 μmol./L |
Total N-Acetylneuraminate b | 1.25–2.50 mmol./L | n-av |
‘Free’ N-Acetylglucosamine | 108 ± 67 nmol./L | n-av |
Glutamate | 24–177 μmol./L | 12–14 μmol./L |
Glutamine | 390–905 μmol./L | 5–42 μmol./L |
Proline | 111–259 μmol./L | 6–158 μmol./L |
Hydroxyproline | 13–40 μmol./L | 0.4–1.5 μmol./L |
Lysine | 105–441 μmol./L | 2–59 μmol./L |
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Grootveld, M.; Percival, B.C.; Page, G.; Hunwin, K.; Bhogadia, M.; Chan, W.; Edgar, M. Updates and Original Case Studies Focused on the NMR-Linked Metabolomics Analysis of Human Oral Fluids Part II: Applications to the Diagnosis and Prognostic Monitoring of Oral and Systemic Cancers. Metabolites 2022, 12, 778. https://doi.org/10.3390/metabo12090778
Grootveld M, Percival BC, Page G, Hunwin K, Bhogadia M, Chan W, Edgar M. Updates and Original Case Studies Focused on the NMR-Linked Metabolomics Analysis of Human Oral Fluids Part II: Applications to the Diagnosis and Prognostic Monitoring of Oral and Systemic Cancers. Metabolites. 2022; 12(9):778. https://doi.org/10.3390/metabo12090778
Chicago/Turabian StyleGrootveld, Martin, Benita C. Percival, Georgina Page, Kayleigh Hunwin, Mohammed Bhogadia, Wyman Chan, and Mark Edgar. 2022. "Updates and Original Case Studies Focused on the NMR-Linked Metabolomics Analysis of Human Oral Fluids Part II: Applications to the Diagnosis and Prognostic Monitoring of Oral and Systemic Cancers" Metabolites 12, no. 9: 778. https://doi.org/10.3390/metabo12090778