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口腔鳞状细胞癌和口腔潜在恶性疾病患者组织标本及唾液中促炎的、NF-κB依赖性细胞因子:IL-1α、IL-6、IL-8和TNF-α的评估

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.

作者信息

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

机构信息

Jagiellonian University Medical College, Faculty of Medicine, Institute of Dentistry, Chair and Department of Periodontology and Clinical Oral Pathology, Montelupich 4, 31-155 Krakow, Poland.

Jagiellonian University Medical College, Faculty of Medicine, Chair of Clinical Biochemistry, Department of Diagnostics, Kopernika 15A, 31-501 Krakow, Poland.

出版信息

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

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.

摘要

背景

口腔鳞状细胞癌(OSCC)是一种危及生命的疾病。它可能由口腔潜在恶性疾病(OPMDs)发展而来。已证实慢性炎症可促进癌变。细胞因子在此过程中起关键作用。本研究的目的是评估OSCC和OPMDs患者组织标本及唾液中的白细胞介素-1α(IL-1α)、白细胞介素-6(IL-6)、白细胞介素-8(IL-8)和肿瘤坏死因子-α(TNF-α)。

方法

通过免疫组织化学评估60例病理病变(OSCC或OPMDs)组织标本和7例对照(正常口腔黏膜,NOM)中的细胞因子,并通过酶联免疫吸附测定评估45例OSCC或OPMDs患者及9例对照(健康志愿者)唾液中的细胞因子。

结果

免疫组织化学分析显示,与NOM相比,OSCC标本中IL-8的表达显著更高,发育异常的OSCC和OPMDs中TNF-α的表达显著更高。此外,无发育异常的口腔白斑和口腔扁平苔藓中TNF-α的表达显著更高,而与NOM相比,仅无发育异常的口腔白斑中IL-8的表达更高。OSCC患者所有评估细胞因子的唾液浓度均显著高于对照组。此外,与对照组相比,发育异常的OPMDs患者唾液中IL-8水平显著更高,与发育异常病变患者相比,OSCC患者唾液中IL-8水平显著更高。与无发育异常的OPMDs患者相比,OSCC患者唾液中IL-6、IL-8和TNF-α的浓度也显著增加。

结论

本研究证实促炎的、NF-κB依赖性细胞因子参与OPMDs和OSCC的发病机制。在所有评估的细胞因子中,口腔黏膜恶性转化过程中最重要的生物标志物似乎是IL-8。需要更大样本量的进一步研究来证实这些结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e70f/7141524/86d93ae2b4c2/jcm-09-00867-g001.jpg

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