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

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.

Current Understanding of the HIF-1-Dependent Metabolism in Oral Squamous Cell Carcinoma

“…Noteworthy, interleukin (IL)-6 and IL8 as well as tumor necrosis factor (TNF)-α contribute to the progression of OSCC [ 37 ]. In particular, IL-8 is the most important factor for malignant transformation in OSCC [ 38 ]. The phenomenon of a HIF-1α mediated stabilization under normoxia upregulating IL-1β has also been published [ 39 ].…”

Animal model and bioinformatics analyses suggest the TIMP1/MMP9 axis as a potential biomarker in oral squamous cell carcinoma

“…Chuanshu et al 26 found that serum SCC‐Ag levels in OSCC (stages III + IV) were significantly higher than those in early tumors or normal subjects. A study of cytokine levels in OSCC illustrated that TNF‐α levels were significantly increased 27 . Kulkarni et al 28 demonstrated that salivary TNF‐α levels increased with the histological grade of OSCC and leukoplakia.…”

“…A study of cytokine levels in OSCC illustrated that TNF-α levels were significantly increased. 27 Kulkarni et al 28 demonstrated that salivary TNF-α levels increased with the histological grade of OSCC and leukoplakia. However, there are no clinical studies on AFP in OSCC.…”

Malignancy history had no marked effect on the prognosis of COVID-19: A cohort study

“…Studies showed that pro-in ammatory cytokines are produced not only by in ammatory cells, but also by tumor cells. Among which, IL-6 was widely involved 33 . In consequence, CRP level in tumor patients was logically elevated.…”