Role of Salivary MicroRNA and Cytokines in the Diagnosis and Prognosis of Oral Squamous Cell Carcinoma
Abstract
:1. Introduction
2. Salivary MicroRNA (miRNA) in OSCC Diagnosis and Prognosis
2.1. Exosomal miRNAs with Diagnostic Capacity
2.2. MiRNAs with Tumor-Suppressor Role
2.3. MiRNAs with Tumor-Activator Role
2.4. Circular RNA in OSCC Diagnosis
3. Salivary Cytokines in OSCC Diagnosis and Prognosis
3.1. IL-6
3.2. IL-8
3.3. TNF-α
3.4. MMP-9
3.5. IL-1-β
3.6. IL-1-Ra
3.7. IL-10
3.8. 8-OHdG (8-Oxo-dG)
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
Abbreviations
OSCC | Oral squamous cell carcinoma |
EVs | Extracellular vesicles |
EZH2 | Enhancer of zeste homolog 2 |
EGFR | Epidermal growth factor receptor |
PKCε | Protein kinase Cε |
TGF | Transforming growth factor |
circRNAs | Circular RNAs |
IL-6 | Interleukin-6 |
TNF-α | Tumor necrosis factor alpha |
IL-8 | Interleukin-8 |
MMP-9 | Matrix metallopeptidase 9 |
IL-1-β | Interleukin-1-β |
IL-1-Ra | IL-1 receptor antagonist |
IL-10 | Interleukin-10 |
8-OHdG (8-oxo-dG) | 8-Oxo-2′-deoxyguanosine |
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Reference | Biomarker | Findings | Clinical Relevance |
---|---|---|---|
[8,9,10,11,12] | miRNA-24- miRNA 3P miRNA412-3p miRNA 512-3p miRNA302b-3p miRNA 517b-3p miRNA 134 miRNA 486-5p miRNA 4484 miRNA 10b-5p miRNA 200a miRNA 365 | Correlated with disease stage, histopathological type, and/or grade of OSCC | Possible tool for the early diagnosis of OSCC; in general, the expression of these miRNAs indicates poor prognosis and higher risk of malignant transformation and oral cancer |
[13,14,15,16,17,18,19,20] | miRNA-27b miRNA-200 miRNA-375 miRNA-26a miRNA-7 miRNA-107 miRNA-218 miRNA let-7 miRNA-125 | Tumor-suppressor role | Increased levels of these biomarkers can be useful for the diagnosis, staging, and prognosis of OSCC; the expression of these miRNAs reduce the progession of OSCC |
[1,21,22,23,24,25,26] | miRNA-21 miRNA-145 miRNA-93 miRNA-184 miRNA-31 miRNA-412-3p miRNA-34a | Tumor-activator role; these miRNAs acts as an oncogenes, promoting OSCC development and progression | Elevated concentrations in the saliva offer a reliable method to detect OSCC and potentially malignant oral lesions |
Reference | Biomarker | Findings | Clinical Relevance |
---|---|---|---|
[38] | IL-6, IL-8 & TNF-α | Notably higher levels of these cytokines in advanced stages of OSCC compared to early stages of the disease; presence of neck metastases associated with increased levels of these molecules. | Possible tool to indicate OSCC progression |
[39] | MMP-9 | Elevated salivary levels of MMP-9 were associated with OSCC Levels of the biomarker decreased dramatically after tumor surgery | MMP-9 as a critical diagnostic and prognostic biomarker for OSCC |
[40] | IL-6, IL-8, IL-1β & TNF-α | Significant differences in levels of IL-6, IL-8, IL-1β, and TNF-α between OSCC patients and to controls | Useful complementary tool for the early detection of OSCC |
[41] | IL-8 | Significantly increased levels of the cytokine in patients with head and neck squamous cell carcinoma; IL-8 levels were positively correlated with the abundance of C. albicans | A salivary microbial and inflammatory biomarker of head and neck squamous cell carcinoma that is influenced by oral health |
[42] | IL-6 & IL-8 | Correlation of qualitative salivary detection of IL-6 and IL-8 between control and disease groups | Probable biomarker for detection of premalignant lesions and OSCC |
[43] | IL-6 & TNF-α | Elevated levels of those cytokines compared to age-matched controls | IL-6 and TNF-α are potential biomarkers for the monitorization of OSCC |
[44] | MMP-9 | MMP-9 levels significantly higher in OSCC patients than in controls or patients with premalignant lesions | Salivary diagnostic biomarker for the detection of premalignant oral lesions and early stages of OSCC |
[45] | MMP-9 | Higher levels of MMP-9 in OSCC patients than in controls | MMP-9 is a good tool for the detection of OSCC |
[46] | IL-8 | Protein concentration of IL-8 was significantly elevated in patients with OSCC than in those with dysplasia and controls | Important marker to discriminate between OSCC and control patients; IL-8 combined with H3F3A mRNA provides good discrimination between OSCC and potentially malignant oral disorders |
[47] | IL-6, IL-8 & TNF-α | Increased levels of these cytokines in patients with oral leukoplakia, submucous fibrosis, and lichen planus than in healthy controls | Diagnostic tool for the detection of premalignant lesions |
[48] | IL-6 | Higher pretreatment levels of IL-6 in patients with oral cancer, associated with better survival | Possible prognosis biomarker |
[49] | IL-6 | Higher salivary levels of IL-6 in OSCC patients when compared with patients with chronic periodontitis, active oral lichen planus, inactive oral lichen planus, or healthy controls | Useful biomarker for the detection of OSCC |
[50] | TNF-α | Increased serum and saliva TNF-α levels in OSCC patients compared with controls and those with premalignant disease | TNF-α as a useful biomarker for OSCC detection; increased levels are associated with histological grade and clinical stage, suggesting a role in the prognosis of OSCC |
[51] | IL-6 | Increased levels | Monitoring of OSCC |
[48] | TNF-α | No differences between control and OSCC group | - |
[52] | IL-6, IL-8 & TNF-α | Higher levels in endophytic squamous cell carcinoma of the tongue than in exophytic squamous cell carcinoma of the tongue, correlated with decreased survival in the endophytic versus exophytic group; IL-6, IL-8, and TNF-α also higher in the exophytic group than in smoking and drinking controls | These biomarkers can identify the progression of squamous cell carcinoma of the tongue from high risk to neoplasm; important biomarker for cancer screening and early detection; correlation between these proteins and survival implies a prognostic benefit potentially useful for management decisions and future target treatments |
[53] | IL-6 & IL-8 | Higher expression in patients with OSCC | Potential tool for OSCC diagnosis |
[54] | IL-6, IL-8 & TNF-α | Increased levels in patients with OSCC and premalignant oral lesions | Proangiogenic and proinflammatory cytokines are elevated in patients with these lesions; diagnosis and prognosis significance of these markers |
[55] | IL-8 & IL-1β | Increased levels in patients with OSCC | Potential use as a diagnostic tool for OSCC |
[56] | IL-8 & IL-1β | Higher levels in OSCC patients, depending on the tumor stage | Increased levels of these biomarkers can be useful for OSCC diagnosis, staging, and prognosis |
[57] | IL-1β | Levels significantly differ between before and after surgery | IL-1β levels may be useful for the detection of early stage OSCC |
[58] | IL-1-Ra | Expression of IL-1-Ra is lower in OSCC and oral dysplasia cells than in normal cells | Possible use as a biomarker for prediction of malignant transformation |
[59] | IL-1-Ra | Expression of IL-1-Ra decreases gradually with the progression of oral dysplasia | IL-1-Ra could be a reliable biomarker for the early diagnosis and follow-up of OSCC; it could be useful to discriminate between premalignant oral lesions and OSCC |
[60] | IL-1-Ra & IL-10 | Salivary IL-10 levels are higher in OSCC patients; IL-1-Ra levels are lower in well-defined tumors than in immature tumors | IL-10 is an interesting tool for diagnosing OSCC, and IL-1-Ra can be helpful for cancer staging |
[61] | IL-10 | High levels of IL-10 expression are found in OSCC, especially in advanced stage tumors and metastatic cells | Salivary IL-10 levels could be used as a biomarker for OSCC diagnosis; a high concentration appears to favor tumor proliferation and dissemination |
[62] | IL-10 | High levels of IL-10 expression correlate with shorter survival, worse prognosis, and increased risk of death | Overexpression of IL-10 is associated with aggressive forms of OSCC, and its level can be used as a survival predictor |
[63] | IL-10 | IL-10 levels increase with tumor progression | Useful as staging biomarker |
[64] | 8-OHdG | 8-OHdG levels are approximately two-fold higher in patients with squamous head and neck cancer than in healthy controls | Quantification of 8-OHdG levels could be used as a diagnostic tool for OSCC |
[65] | 8-OHdG | 8-OHdG levels are more than two-fold higher in in OSCC patients than in controls | 8-OHdG can be used as DNA damage biomarker to assess disease progression |
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Manzano-Moreno, F.J.; Costela-Ruiz, V.J.; García-Recio, E.; Olmedo-Gaya, M.V.; Ruiz, C.; Reyes-Botella, C. Role of Salivary MicroRNA and Cytokines in the Diagnosis and Prognosis of Oral Squamous Cell Carcinoma. Int. J. Mol. Sci. 2021, 22, 12215. https://doi.org/10.3390/ijms222212215
Manzano-Moreno FJ, Costela-Ruiz VJ, García-Recio E, Olmedo-Gaya MV, Ruiz C, Reyes-Botella C. Role of Salivary MicroRNA and Cytokines in the Diagnosis and Prognosis of Oral Squamous Cell Carcinoma. International Journal of Molecular Sciences. 2021; 22(22):12215. https://doi.org/10.3390/ijms222212215
Chicago/Turabian StyleManzano-Moreno, Francisco Javier, Victor J. Costela-Ruiz, Enrique García-Recio, Maria Victoria Olmedo-Gaya, Concepción Ruiz, and Candelaria Reyes-Botella. 2021. "Role of Salivary MicroRNA and Cytokines in the Diagnosis and Prognosis of Oral Squamous Cell Carcinoma" International Journal of Molecular Sciences 22, no. 22: 12215. https://doi.org/10.3390/ijms222212215