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. 2020 Mar 21;9(3):867.
doi: 10.3390/jcm9030867.

Evaluation of Proinflammatory, NF-kappaB Dependent Cytokines: IL-1α, IL-6, IL-8, and TNF-α in Tissue Specimens and Saliva of Patients with Oral Squamous Cell Carcinoma and Oral Potentially Malignant Disorders

Karolina Babiuch  1 , Beata Kuśnierz-Cabala  2 , Barbara Kęsek  1 , Krzysztof Okoń  3 , Dagmara Darczuk  1 , Maria Chomyszyn-Gajewska  1
Affiliations

Evaluation of Proinflammatory, NF-kappaB Dependent Cytokines: IL-1α, IL-6, IL-8, and TNF-α in Tissue Specimens and Saliva of Patients with Oral Squamous Cell Carcinoma and Oral Potentially Malignant Disorders

Karolina Babiuch et al. J Clin Med. .

Abstract

Background: Oral squamous cell carcinoma (OSCC) is a life-threatening disease. It could be preceded by oral potentially malignant disorders (OPMDs). It was confirmed that chronic inflammation can promote carcinogenesis. Cytokines play a crucial role in this process. The aim of the study was to evaluate interleukin-1alpha (IL-1α), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor alpha (TNF-α) in tissue specimens and saliva of patients with OSCC and OPMDs.

Methods: Cytokines were evaluated in 60 tissue specimens of pathological lesions (OSCCs or OPMDs) and in 7 controls (normal oral mucosa, NOM) by immunohistochemistry and in saliva of 45 patients with OSCC or OPMDs and 9 controls (healthy volunteers) by enzyme-linked immunosorbent assays.

Results: Immunohistochemical analysis revealed significantly higher expression of IL-8 in OSCC specimens and TNF-α in OSCCs and OPMDs with dysplasia as compared to NOM. Moreover, expression of TNF-α was significantly higher in oral leukoplakia and oral lichen planus without dysplasia, whereas expression of IL-8 only in oral leukoplakia without dysplasia in comparison with NOM. Salivary concentrations of all evaluated cytokines were significantly higher in patients with OSCC than in controls. Moreover, levels of IL-8 were significantly higher in saliva of patients with OPMDs with dysplasia as compared to controls and in OSCC patients as compared to patients with dysplastic lesions. There was also significant increase in salivary concentrations of IL-6, IL-8 and TNF-α in patients with OSCC as compared to patients with OPMDs without dysplasia.

Conclusion: The study confirmed that proinflammatory, NF-kappaB dependent cytokines are involved in pathogenesis of OPMDs and OSCC. The most important biomarker of malignant transformation process within oral mucosa among all assessed cytokines seems to be IL-8. Further studies on a larger sample size are needed to corroborate these results.

Keywords: biomarkers; cytokines; inflammation; oral potentially malignant disorders; oral squamous cell carcinoma.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
IL-1α—moderate brown staining in all epithelial cells of oral squamous cell carcinoma (OSCC) (20x).
Figure 2
Figure 2
IL-1α—moderate brown staining in epithelum (all layers) of oral leukoplakia without dysplasia (OL) (20x).
Figure 3
Figure 3
IL-6—moderate brown staining in epithelium (all layers) and strong staining in stroma of oral epithelial dysplasia (OED) (20x).
Figure 4
Figure 4
IL-8—moderate brown staining in epithelial cells and stroma of OSCC (40x).
Figure 5
Figure 5
IL-8—weak brown staining in stroma of OED (40x).
Figure 6
Figure 6
TNF-α—strong brown staining in epithelial cells of OSCC (40x).
Figure 7
Figure 7
TNF-α—moderate brown staining in stroma of OSCC (40x).
Figure 8
Figure 8
TNF-α—strong brown staining in epithelium (basal and parabasal layer) and stroma of oral lichen planus without dysplasia (OLP) (20x).
Figure 9
Figure 9
Salivary levels of IL-1α (a), IL-6 (b), IL-8 (c), and TNF-α (d) in control group (CG) and patients with oral lichen planus without dysplasia (OLP), oral leukoplakia without dysplasia (OL), oral epithelial dysplasia (OED), or oral squamous cell carcinoma (OSCC); the median and interquartile range (box), and percentile 5–95% range (whiskers) are shown; * means significant difference vs. CG; ꝏ means significant difference vs. OSCC (p < 0.05).
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References

    1. Du M., Nair R., Jamieson L., Liu Z., Bi P. Incidence Trends of Lip, Oral Cavity, and Pharyngeal Cancers: Global Burden of Disease 1990–2017. J. Dent. Res. 2019;24:22034519894963. doi: 10.1177/0022034519894963. - DOI - PubMed
    1. Johnson N.W., Warnakulasuriya S., Gupta P.C., Dimba E., Chindia M., Otoh S.C., Sankaranarayaranan R., Califano J., Kowalski L. Global oral health inequalities in incidence and outcomes for oral cancer: Causes and solutions. Adv. Dent. Res. 2011;23:237–246. doi: 10.1177/0022034511402082. - DOI - PubMed
    1. McGuire S. World cancer report 2014. Geneva, Switzerland: World Health Organization, international agency for research on cancer, WHO Press, 2015. Adv. Nutr. 2016;7:418–419. doi: 10.3945/an.116.012211. - DOI - PMC - PubMed
    1. Petruzzi M.N.M.R., Cherubini K., Salum F.G., de Figueiredo M.A.Z. Role of tumor-associated macrophages in oral squamous cells carcinoma progression: An update on current knowledge. Diagn. Pathol. 2017;12:32. doi: 10.1186/s13000-017-0623-6. - DOI - PMC - PubMed
    1. El-Naggar A.K., Chan J.K.C., Grandis J.R., Takata T., Slootweg P.J. WHO Classification of Head and Neck Tumours. 4th ed. International Agency for Research on Cancer; Lyon, France: 2017. pp. 105–131.

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