Table 1.
Studies of saliva-based biomarkers.
| Cancer Location | Study Design | Patients (No.) | Saliva Collection | Methods | Biomarkers | References |
|---|---|---|---|---|---|---|
| Brain Cancer | Biochemical | 28 C, 32 B, 42 HC | Unstimulated | Spectrophotometric | FRAP, protein thiols | [20] |
| Pancreatic Cancer | Transcriptomic | DP: 12 C, 12 HC | Unstimulated | DP: Affymetrix U133 Plus 2.0 Array | MBD3L2, KRAS, STIM2, DMXL2, ACRV1, DMD, CABLES1, TK2, GLTSCR2, CDKL3, TPT1, DPM1 | [10] |
| VP: 30 C, 30 P, 30 HC | VP: RT-qPCR | |||||
| Metabolomic | 18 C, 87 HC | Unstimulated | CE-TOF-MS | Leucine with isoleucine tryptophan, valine, glutamic acid, phenylalanine, glutamine, aspartic acid | [21] | |
| Microbial | DP: 10 C, 10 HC | Unstimulated | DP: HOMIM | Neisseria elongata, Streptococcus mitis, Granulicatella adiacens | [22] | |
| VP: 28 C, 27 P, 28 HC | VP: RT-qPCR | |||||
| miRNAs | 30 C, 32 HC | NA | miScript miRNA PCR array human, RT-qPCR | miR-17, miR-21, miR-181a, miR-181b, miR-196a | [23] | |
| miRNAs | DP: 8 C, 8 HC | Stimulated (citric acid) | DP: Human miRNA Microarray, release 19.0 (Agilent) | miR-3679-5p, miR-940 | [12] | |
| VP: 40 C, 20 B, 40 HC | VP: RT-qPCR | |||||
| miRNAs | 7 C, 4 P, 2 IPMN, 4 HC | NA | RT-qPCR using Fluidigm (Biomark) | miR-21, miR-23a, miR-23b, miR-29c, miR-216 | [24] | |
| Microbial | 8 C, 78 OD, 22 HC | NA | RT-qPCR | Leptotrichia sp. to Porphyromonas sp. | [25] | |
| Lung Cancer | Proteomic | DP: 10 C, 10 HC | Unstimulated | DP: 2D-DIGE-MS | HP, AZGP1, human calprotectin | [9] |
| VP: 26 C, 26 HC | VP: Western blotting, ELISA kits | |||||
| Transcriptomic | DP: 10 C, 10 HC | Unstimulated | DP: Affymetrix HG U133 Plus 2.0 Array | BRAF, CCNI, EGFR, FGF19, FRS2, GREB1, LZTS1 | [26] | |
| VP: 23 C, 64 HC | VP: RT-qPCR | |||||
| Proteomic | 21 C, 20 HC | Unstimulated | Surface-enhanced Raman spectroscopy | Amino acids, nucleic acid bases | [27] | |
| Gastric Cancer | Proteomic | 23 C, 18 HC | NA | MALDI-TOF-MS | 1472.78 Da, 2936.49 Da, 6556.81 Da, 7081.17 Da | [28] |
| Oesophageal Cancer | miRNAs | DP: 8 EC, 4 HC | Stimulated (2% citric acid) | DP: RT-qPCR | miR-21 | [29] |
| VP: 32 C, 16 HC | VP: RT-qPCR | |||||
| miRNAs | DP: 7 C, 3 HC | Stimulated (2% citric acid) | DP: Agilent microarray | miR-144, miR-10b, miR-451, miR-21 | [11] | |
| VP: 39 C, 19 HC | VP: RT-qPCR | |||||
| miRNAs | 67 C, 50 HC | Stimulated (2% citric acid) | RT-qPCR | miR-144 | [30] | |
| miRNAs | 100 C, 50 HC | Stimulated (citric acid) | RT-qPCR | miR-21 | [31] | |
| Breast Cancer | Proteomic | 52 active BC, 22 non-active BC, 33 HC | Stimulated (lemon juice when necessary) | ER-EIA (Abbott) | EGF | [32] |
| Proteomic | 12 C, 8 B, 15 HC | Stimulated (cube of paraffin) | EIA kits, ELISA kits (Oncogene Research) | CA15-3, c-erbB-2 | [33] | |
| Proteomic | 30 C, 44 B, 57 HC | Stimulated (gum base) | ELISA kits and EIA kits | c-erbB-2 | [34] | |
| Proteomic | 49 C, 49 HC | Unstimulated | ELISA kits | VEGF, EGF, CEA | [35] | |
| Proteomic | 10 C, 10 B, 10 HC | Stimulated (paraffin or gum base) | IL-LC-MS/MS | 40 protein profiles | [36] | |
| Proteomic | 26 C, 35 HC | Unstimulated | EIA kits | CA15-3 | [37] | |
| Proteomic | 20 C, 10 HC | Stimulated (paraffin or gum base) | IL-LC-MS/MS | 20 proteins (Stage IIa) 28 proteins (Stage IIb) |
[38] | |
| Transcriptomic | DP: 10 C, 10 HC | Unstimulated | DP: Affymetrix HG U133 Plus 2.0 Array | CSTA, TPT1, IGF2BP1, GRM1, GRIK1, H6PD, MDM4, S100A8 | [13] | |
| VP: 30 C, 63 HC | VP: RT-qPCR | |||||
| Proteomic | DP: 10 C, 10 HC | DP: 2D-DIGE | CA6 | |||
| VP: 30 C, 63 HC | VP: Western blotting | |||||
| Metabolomic | 30 C, 87 HC | Unstimulated | CE-MS | 28 metabolites | [21] | |
| Proteomic | 20 C, 10 HC | NA | LC-MS/MS | Protein profile | [39] | |
| Proteomic | 27 C, 28 HC | Unstimulated | UPLC-MS | 15 SFAAs | [40] | |
| Proteomic | 16 C, 16 HC | Stimulated (gum base) | Gel electrophoresis and western blotting | Lung resistance protein | [41] | |
| Metabolomic | 111 C, 61 HC | NA | UPLC-MS/MS | Polyamines | [42] | |
| Prostate Cancer | Proteomic | 11 high serum PSA prostate C, 20 low serum PSA prostate C | Stimulated (citrate-containing cotton) | ELISA | PSA | [43] |
| Leukaemia | Transcriptomic | 7 C, 20 HC | Stimulated (citric acid) | RT-qPCR | BCR-ABL, PML-RARα, AML-ETO | [44] |
| Biochemical | 32 C, 115 HC | Unstimulated | Biochemical analysis, EIA, chemoluminescence | ALP, T4, TSH, IgA | [45] | |
| Ovarian Cancer | Transcriptomic | DP: 11 C, 11 HC | Unstimulated | DP: Affymetrix HG U133 Plus 2.0 Array | H3F3A, SRGN, B2M, BASP1, AGPAT1, IL1B, IER3 | [46] |
| VP: 21 C, 35 HC | VP: RT-qPCR | |||||
| Proteomic | 92 B, 41 C, 55 HC | NA | Radioimmunoassay | CA 125 | [47] |
Abbreviations: DP, discovery phase; VP, validation phase; C, cancer; P, pancreatitis; HC, healthy controls; IPMN, intraductal papillary mucinous neoplasia; OD, other diseases; SFAAs, salivary free amino acids; PSA, prostate-specific antigen; VEGF, vascular endothelial growth factor; EGF, epidermal growth factor; CEA, carcinoembryonic antigen; NA, not available; FRAP, ferric acid reducing ability; RT-qPCR, reverse transcription–PCR; CE-TOF-MS, capillary electrophoresis and time-of-flight/mass spectrometry; HOMIM, Human Oral Microbe Identification Microarray; 2D-DIGE-MS, 2-dimensional difference gel electrophoresis and mass spectrometry; ELISA, enzyme-linked immunosorbent assay; MALDI-TOF-MS, matrix-assisted laser desorption ionisation time-of-flight/mass spectrometry; ER-EIA, oestrogen receptor enzyme immunoassay; IL-LC-MS/MS, isotopic labelling coupled with liquid chromatography tandem mass spectrometry; UPLC-MS/MS, ultra-performance liquid chromatography tandem mass spectrometry.