Table 2.
Metabolic salivary biomarkers.
| Author | Country | Number of samples | Biomarker category | Saliva collection time | Saliva collection method | Sample processing | Test method | Results |
|---|---|---|---|---|---|---|---|---|
| Lohavanichbutr et al. [60] | USA | 101 OSCC patients/58 OPC patients/35 healthy patients | Metabolites | — | Unstimulated | Centrifuged at 1300 × g/10 min/4 °C. Stored at -80°C. |
LC-MS | The levels of two metabolites (glycine and proline) to be significantly different between OCC and controls but did not find any appreciable differences in metabolite levels between OPC and controls or between OCC with and without nodal metastasis. Four metabolites, glycine, proline, citrulline, and ornithine were associated with early-stage OCC. |
| Monedeiro et al. [18] | Poland | 5 OSCC patients/15 healthy patients | VOCs | Between 8 and 12 AM | Unstimulated | Stored at -80°C. | HS-SPME + GC-MS analysis | 1-octen-3-ol, hexanoic acid, E-2-octenal, heptanoic acid, octanoic acid, E-2-nonenal, nonanoic acid, 2,4-decadienal and 9-undecenoic acid. Obtained overall accuracy was 90%. Oral cancer cases were predicted with 100% of sensitivity and specificity. |
| Shigeyama et al. [63] | Japan | 24 OSCC patients/50 healthy patients | VOCs | For at least 1.5 h after meals for multiple (1–3) time periods up to surgery after hospitalization | Unstimulated | Stored at −80°C. | TFME method + GC-MS | 12 potential BM of oral cancer detection: -decreased levels: Ethanol, 2-Pentanone, phenol, Hexadecanoic acid. -disappeared levels: Undecane, 1-octanol, Butyrolactone, benzyl alcohol. -new VOCs production: 3-Heptanone, 1,3-Butanediol, 1,2-Pentanediol, 1-Hexadecanol. |
| Song et al. [58] | China | 249 (124 OPMD, 125 OSCC)/124 healthy patients | Metabolites | Multiple | Unstimulated | Centrifuged at 5000 rpm/3 min. Stored at -80°C. |
CPSI-MS | Putrescine, cadaverine, thymidine, adenosine, 5-aminopentoate, hippuric acid, phosphocholine, glucose, serine, adrenic acid showed changes in their levels (increasing or decreasing) during malignant progression from health to OSCC. |
| Ohshima et al. [62] | Japan | 22 OSCC patients/21 healthy patients | Metabolites | Early morning 8 : 00 a.m. |
Unstimulated | Centrifuged at 2600 × g/15 min/4 °C, and spun for a further 20 min. | CE-TOF/MS | Choline, BBCAs, urea, and 3-hydroxybutyric acid were statistically significant in the detection of OSCC. |
| Ishikawa et al. [59] | Japan | 24 oral cancer patients/44 healthy patients | Metabolites | 08 : 00 am–12:00 | Unstimulated whole saliva. | Centrifuged at 9100 × g for at least 2.5 h/4°C Stored at −80°C |
CE-TOF/MS | Combination of Pipecolato and S-adenosylmethionine yielded a high area under receiver operating characteristic curves for discriminating oral cancers from controls. |
| Sharma et al. [23] | India | 55 (30 OPMD y 25 OSCC) patients/30 healthy patients | Monosaccharids | Early morning | Unstimulated | Centrifuged at - Stored at -80°C. |
Spectrophotometry | Significantly higher L-fucose levels in OPML and OSCC groups in saliva. |
OSCC: oral squamous cell carcinoma; OPMD: oral potentially malignant disorders; VOCs: volatile organic compounds; HS-SPME+GC-MS: headspace-solid phase microextraction and analyzed using gaschromatography-mass spectrometry; TFME method+GC: thin-film microextraction method and chromatographic analysis with mass spectrometric; LC-MS: Liquid chromatography–mass spectrometry; CPSI-MS: conductive polymer spray ionization mass spectrometry; CE-TOF/MS: capillary electrophoresis time-of-flight mass spectrometry; BCAA: metabolites in the branched chain amino acids cycle.