Salivary Extracellular Vesicles: Biomarkers and Beyond in Human Diseases
Abstract
:1. Introduction
2. Characteristics of sEVs
2.1. Types of EV
2.1.1. Exosomes
2.1.2. MVs
2.1.3. Apoptotic Bodies
2.2. Origins of sEVs
2.2.1. Cellular Origin
2.2.2. Glandular Origin
2.2.3. Circulatory Origin
2.2.4. Bacterial Origin
2.3. Structure of sEVs
2.4. Isolation of sEVs
3. Roles of sEVs in Human Diseases
3.1. Biomarkers
3.1.1. Oral Diseases
Oral Cancers
Periodontal Disease
Primary Sjögren’s Syndrome
Oral Lichen Planus
Disease | Type | Potential Biomarker | Expression | Application | AUC of ROC Curve | Ref. | Year |
---|---|---|---|---|---|---|---|
OC | Protein | CD81 and CD9 | Downregulated | Diagnosis | / | [94,95] | 2011; 2016 |
CD63 | Upregulated | Diagnosis | / | [94] | 2016 | ||
Alix | Upregulated | Diagnosis | AUC = 0.712 | [96] | 2021 | ||
Three full proteins (HEP2, NHERF-2, and MMP25) and three phosphoproteins (PGM 1, ACLY, and KPCD) | Upregulated | Assessing OSCC therapeutical outcomes | / | [97] | 2023 | ||
OC | RNA | miR-1307-5p | Upregulated | Diagnosis and suggesting poor prognosis | / | [98] | 2022 |
miR-24-3p | Upregulated | Diagnosis | AUC = 0.738, p = 0.02 | [99] | 2020 | ||
miR-486-5p | Upregulated | Diagnosis | AUC = 0.67, p = 0.05 | [100] | 2022 | ||
miR-10b-5p | Downregulated | Diagnosis | AUC = 0.58, p = 0.33 | [100] | 2022 | ||
miR-140-5p, miR-143-5p and miR-145-5p | Downregulated | Diagnosis | (Combination of these three RNAs) AUC of 0.93 (p < 0.0001) | [102] | 2023 | ||
Periodontal disease | Protein | CD9, CD81 | Downregulated | Diagnosis | / | [113] | 2019 |
Complement components and chemokine ligand 28 | Upregulated | Diagnosis | / | [114] | 2020 | ||
RNA | hsa-miR-125a-3p | Downregulated | Diagnosis of CP | AUC = 1, p = 0.02 | [115] | 2020 | |
miR-223-3p | Downregulated | Diagnosis and assessing its severity | / | [21] | 2021 | ||
PD-L1 mRNA | Upregulated | Diagnosis and assessing its severity | / | [116] | 2019 | ||
Periodontal disease | RNA | hsa-miR-5571-5p | Upregulated | Monitoring and diagnosing the progression of periodontitis | AUC = 0.849, p < 0.001 | [117] | 2021 |
hsa-let-7f-5p | Downregulated | AUC = 0.705, p = 0.02 | |||||
hsa-miR-99a-5p | Downregulated | AUC = 0.747, p = 0.0054 | |||||
hsa-miR-28-5p | Downregulated | AUC = 0.711, p = 0.017 | |||||
hsa-miR-320d | Downregulated | AUC = 0.705, p = 0.02 | |||||
hsa-miR-140-5p, hsa-miR-628-5p, and hsa-miR-146a-5p | Upregulated | (Panel of three miRNAs) diagnosis of periodontal disease status | AUC = 0.96, p < 0.0001 for periodontitis; AUC = 0.78, p = 0.0006 for gingivitis | [118] | 2020 | ||
/ | Global 5mC hypermethylation | Significantly increased | Diagnosis of periodontitis | AUC = 1, p = 0.001 | [119] | 2021 | |
PSS | Protein | APMAP, GNA13, WDR1, SIRPA, LSP1 | Upregulated | Diagnosis and prognosis evaluation and disease monitoring | / | [122] | 2017 |
S100A7, S100A8, S100A9, S100A11, and S100A12, RETN, SERPINB1 and SERPINB5, AZU1, CD14, ANXA2, CFL-1, LCP1, MIF | Upregulated | Diagnosis | / | [123] | 2021 | ||
OLP | RNA | miR-4484 | Upregulated | Diagnosis | / | [125] | 2015 |
3.1.2. Non-Oral Diseases
Lung Cancer
Other Cancers
Neurodegenerative Diseases
Traumatic Brain Injury
Mental Disorders
Disease | Type | Potential Biomarker | Expression | Application | AUC of ROC Curve | Ref. | Year | ||
---|---|---|---|---|---|---|---|---|---|
Lung cancer | Protein | Differentially expressed phosphopeptides | 37 phosphopeptides were upregulated | Diagnosis | / | [131] | 2022 | ||
Differentially expressed phosphopeptides | 217 phosphopeptides were downregulated | Diagnosis | |||||||
Other cancers | Esophageal cancer | RNA | seG-NchiRNA | Upregulated | Diagnosis and evaluating treatment response and risk of recurrence | AUC = 0.912 p < 0.001 | [134] | 2019 | |
Other cancers | Esophageal cancer | RNA | A combination of a tsRNA (tRNA-GlyGCC-5) and a previously undocumented small RNA | Upregulated | Diagnosis and prognosis and guiding therapy | / | [135] | 2022 | |
Pancreaticobiliary carcinoma | RNA | miR-1246 and miR-4644 | Upregulated | Diagnosis | The combination of these two RNAs showed AUC = 0.833 p = 0.005 | [136] | 2016 | ||
Prostate cancer | RNA | miR-331-3p and miR-200b | Downregulated | Diagnosis | AUC = 0.663 (miR-200b); AUC = 0.648 (miR-331-3p) | [137] | 2022 | ||
Neurodegenerative diseases | PD | Protein | α-synuclein | Upregulated | Diagnosis | / | [140] | 2019 | |
Neurodegenerative diseases | PD | Protein | α-synOlig | Upregulated | Diagnosis | AUC = 0.941 | [141] | 2019 | |
ALS | Protein | ZNF428 | Downregulated | Diagnosis | / | [144] | 2023 | ||
TBI | Gene | CDC2, CSNK1A1 and CTSD | Upregulated | Diagnosis of mild TBI | / | [145] | 2019 | ||
ALOX5, ANXA3, CASP1, IL2RG, ITGAM, ITGB2, LTA4H, MAPK14, and TNFRSF1A | Upregulated | Diagnosis and assessing the severity of TBI | / | [147] | 2020 | ||||
Mental disorders | Protein | GPM6a | Upregulated | Diagnosis of stress and monitoring therapeutic effect | / | [149] | 2020 | ||
Gene | PGK1 | Upregulated | Assessing fatigue levels | / | [150] | 2022 |
3.1.3. Physiological Condition: Age
3.2. Non-Biomarker Functions
3.2.1. Innate Immune Defense
3.2.2. Hemostasis
3.2.3. Therapy
3.2.4. Carrier for Drug Delivery Systems
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Wu, J.; Liu, G.; Jia, R.; Guo, J. Salivary Extracellular Vesicles: Biomarkers and Beyond in Human Diseases. Int. J. Mol. Sci. 2023, 24, 17328. https://doi.org/10.3390/ijms242417328
Wu J, Liu G, Jia R, Guo J. Salivary Extracellular Vesicles: Biomarkers and Beyond in Human Diseases. International Journal of Molecular Sciences. 2023; 24(24):17328. https://doi.org/10.3390/ijms242417328
Chicago/Turabian StyleWu, Jialing, Gege Liu, Rong Jia, and Jihua Guo. 2023. "Salivary Extracellular Vesicles: Biomarkers and Beyond in Human Diseases" International Journal of Molecular Sciences 24, no. 24: 17328. https://doi.org/10.3390/ijms242417328