血清IL-6、IL-17、TNF-α和IFN-γ水平与60例口腔鳞癌患者临床特征关系探讨

doi:10.19438/j.cjoms.2022.02.007

摘要/Abstract

摘要： 目的:探讨IL-6、IL-17、TNF-α和IFN-γ水平与口腔鳞癌（oral squamous cell carcinoma, OSCC）患者临床特征的关系。方法:选择2019—2021年就诊于新疆维吾尔自治区人民医院颌面外科的OSCC患者60例,非OSCC患者60例,同期健康体检者60例。抽取空腹外周血2 mL,使用流式细胞仪检测IL-6、IL-17、TNF-α和IFN-γ水平,分析血清4种细胞因子与OSCC患者临床特征的关系以及在3组间的表达差异,采用SPSS 22.0软件包对数据进行统计学分析。结果:OSCC患者术前血清IL-6、IL-17、TNF-α,IFN-γ的表达水平与性别、淋巴结转移和分化程度无显著相关关系（P>0.05）。IL-6、IL-17、TNF-α表达与TNM分期和肿瘤大小存在显著关系（P<0.05）,而IFN-γ表达与TNM分期和肿瘤大小无显著关系（P>0.05）。OSCC患者术前血清IL-6、IL-17、TNF-α表达水平显著高于非OSCC患者和正常组（P<0.05）;IFN-γ水平显著低于非OSCC患者和正常对照组（P<0.05）。诊断价值分析显示,IL-6、IL-17、TNF-α、IFN-γ联合检测后敏感度、阳性预值均显著提高。结论:血清IL-6、IL-17、TNF-α和IFN-γ水平与口腔鳞癌患者临床特征存在一定关系。

关键词: 口腔鳞癌, IL-6, IL-17, TNF-α, IFN-γ, 细胞因子

Abstract: PURPOSE: To investigate the relationship between serum IL-6, IL-17, TNF-α and IFN-γ levels and clinical characteristics of patients with oral squamous cell carcinoma(OSCC). METHODS: A total of 60 patients with OSCC and 60 patients with non-OSCC, who diagnosed at the People's Hospital of Xinjiang Uygur Autonomous Region from 2019 to 2021 were enrolled in the study; at the same time, 60 healthy people for normal physical examination were chosen as the control group, expression levels of IL-6, IL-17, TNF-α and IFN-γ were detected by flow cytometer, the relationship between serum IL-6, IL-17, TNF-α, IFN-γ levels and clinical features of OSCC patients was analyzed. Statistical analysis was performed with SPSS 22.0 software package. RESULTS: The levels of IL-6, IL-17, TNF-α in OSCC patients was positively associated with TNM stage and tumor size(P<0.05). No change was seen in IFN-γ in OSCC patients compared to other two groups(P>0.05). The concentration of IL-6, IL-17, TNF-α in OSCC patients were significantly higher than that in the non-OSCC group and the control group(P<0.05). The level of IFN-γ in OSCC patients were significantly lower than that in the control group (P<0.05). Diagnostic value analysis showed that the sensitivity and positive predictive value of IL-6, IL-17, TNF-α, IFN-γ were significantly improved. CONCLUSIONS: Serum IL-6, IL-17, TNF-α, IFN-γ levels may be related to the clinical characteristics of patients with OSCC.

Key words: Oral squamous cell carcinoma, IL-6, IL-17, TNF-α, IFN-γ, Cytokines

中图分类号:

R739.8

努尔曼古丽·牙森, 多力昆·吾甫尔, 白尔娜·吾守尔, 闫广鹏. 血清IL-6、IL-17、TNF-α和IFN-γ水平与60例口腔鳞癌患者临床特征关系探讨[J]. 中国口腔颌面外科杂志, 2022, 20(2): 141-145.

NUERMANGULI·Yasen, DUOLIKUN·Wufuer, BAIERNA·Wushuoer, YAN Guang-peng. The relationship between serum IL-6, IL-17, TNF-α, IFN-γ levels, clinical characteristics of60patients with oral squamous cell carcinoma[J]. China J Oral Maxillofac Surg, 2022, 20(2): 141-145.

参考文献

[1] Petersen PE.Oral cancer prevention and control--the approach of the World Health Organization[J]. Oral Oncol, 2009, 45(4-5): 454-460.
[2] Wang R, Yuan Y, Zhou Y, et al.Screening diagnostic biomarkers of OSCC via an LCM-based proteomic approach[J]. Oncol Rep, 2018, 40(4): 2088-2096.
[3] Petruzzi MN, Cherubini K, Salum FG, et al.Role of tumour-associated macrophages in oral squamous cells carcinoma progression: an update on current knowledge[J]. Diagn Pathol, 2017, 12(1): 32-39.
[4] Scheff NN, Ye Y, Bhattacharya A, et al.Tumor necrosis factor alpha secreted from oral squamous cell carcinoma contributes to cancer pain and associated inflammation[J]. Pain, 2017, 158(12): 2396-2409.
[5] Multhoff G, Molls M, Radons J, et al.Chronic inflammation in cancer development[J]. Front Immunol, 2011, 2: 98-114.
[6] Sun X, Xiang CJ, Wu J, et al.Relationship between serum inflammatory cytokines and lifestyle factors in gastric cancer[J]. Mol Clin Oncol, 2019, 10(3): 401-414.
[7] Babiuch K, Kusnierz-Cabala B, Kesek B, et al.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[J]. J Clin Med, 2020, 9(3): 867-884.
[8] Henry CJ, Sedjo RL, Rozhok A, et al.Lack of significant association between serum inflammatory cytokine profiles and the presence of colorectal adenoma[J]. BMC cancer, 2015, 15(14): 123-131.
[9] Fernández-Olavarría A, Mosquera-Pérez R, Díaz-Sánchez RM, et al.The role of serum biomarkers in the diagnosis and prognosis of oral cancer: a systematic review[J]. J Clin Exp Dent, 2016, 8(2): e184-e193.
[10] Nardinocchi L, Sonego G, Passarelli F, et al.Interleukin-17 and interleukin-22 promote tumor progression in human nonmelanoma skin cancer[J]. Eur J Immunol, 2015, 45(3): 922-931.
[11] 江明明, 夏海龙. IL-17在多发性骨髓瘤患者骨髓中的表达及在其发病机制中的作用[J]. 中国实验血液学杂志, 2019, 27(4): 1154-1158.
[12] Zhang ZS, Gu Y, Liu BG, et al.Oncogenic role of Tc17 cells in cervical cancer development[J]. World J Clin Cases, 2020, 8(1): 11-19.
[13] Swierczyński M, Szymaszkiewicz A, Fichna J, et al.New insights into molecular pathways in colorectal cancer: adiponectin, interleukin-6 and opioid signaling[J]. Biochim Biophys Acta Rev Cancer, 2021, 1875(1): 188460.
[14] Zanini D, Manfredi LH, Pelinson LP, et al.ADA activity is decreased in lymphocytes from patients with advanced stage of lung cancer[J]. Med Oncol, 2019, 36(9): 78-87.
[15] Andersen BL, Goyal NG, Weiss DM, et al.Cells, cytokines, chemokines, and cancer stress: a biobehavioral study of patients with chronic lymphocytic leukemia[J]. Cancer, 2018, 124(15): 3240-3248.
[16] 刘盼, 多力昆·吾甫尔, 蔡志刚, 等. 维吾尔族口腔鳞状细胞癌患者中血清鳞状细胞癌抗原的表达研究[J]. 国际口腔医学杂志, 2016, 43(6): 645-650.
[17] Roi A, Roi CI, Negrutiu ML, et al.The challenges of OSCC diagnosis: salivary cytokines as potential biomarkers[J]. J Clin Med, 2020, 9(9): 2866-2883.
[18] Rai AK, Panda M, Das AK, et al.Dysbiosis of salivary microbiome and cytokines influence oral squamous cell carcinoma through inflammation[J]. Arch Microbiol, 2021, 203(1): 137-152.
[19] Arduino PG, Menegatti E, Cappello N, et al.Possible role for interleukins as biomarkers for mortality and recurrence in oral cancer[J]. Int J Biol Markers, 2015, 30(2): e262-e266.
[20] Chen J, Li X, Huang CL, et al.Change of serum inflammatory cytokines levels in patients with chronic obstructive pulmonary disease, pneumonia and lung cancer[J]. Technol Cancer Res Treat, 2020, 19: 1533033820951807.
[21] Lisa Cheng YS, Jordan L, Gorugantula LM, et al.Salivary interleukin-6 and -8 in patients with oral cancer and patients with chronic oral inflammatory diseases[J]. J Periodontol, 2014, 85(7): 956-965.
[22] Trikha M, Corringham R, Klein B, et al.Targeted anti-interleukin-6 monoclonal antibody therapy for cancer: a review of the rationale and clinical evidence[J]. Clin Cancer Res, 2003, 9(13): 4653-4665.
[23] Bachelot T, Ray-Coquard I, Menetrier-Caux C, et al.Prognostic value of serum levels of interleukin 6 and of serum and plasma levels of vascular endothelial growth factor in hormone-refractory metastatic breast cancer patients[J]. Br J Cancer, 2003, 88(11): 1721-1726.
[24] Grivennikov S, Karin M.Autocrine IL-6 signaling: a key event in tumorigenesis?[J]. Cancer Cell, 2008, 13(1): 7-9.
[25] Hosking MP, Flynn CT, Whitton JL, et al.Antigen-specific naive CD8+ T cells produce a single pulse of IFN-γ in vivo within hours of infection, but without antiviral effect[J]. J Immunol, 2014, 193(4): 1873-1885.
[26] Salerno F, Guislain A, Cansever D, et al.TLR-mediated innate production of IFN-γ by CD8+ T cells is independent of glycolysis[J]. J Immunol, 2016, 196(9): 3695-3705.
[27] Pötzl J, Roser D, Bankel L, et al.Reversal of tumor acidosis by systemic buffering reactivates NK cells to express IFN-γ and induces NK cell-dependent lymphoma control without other immunotherapies[J]. Int J Cancer, 2017, 140(9): 2125-2133.
[28] Zhang S, Wang X, Gupta A, et al.Expression of IL-17 with tumor budding as a prognostic marker in oral squamous cell carcinoma[J]. Am J Transl Res, 2019, 11(3): 1876-1883.
[29] Wei T, Cong X, Wang XT, et al.Interleukin-17A promotes tongue squamous cell carcinoma metastasis through activating miR-23b/versican pathway[J]. Oncotarget, 2017, 8(4): 6663-6680.
[30] Jablońska E, Kiluk M, Piotrowski L, et al.Tumor necrosis factor-alpha and soluble tumor necrosis factor receptors in the culture supernatants of polymorphonuclear cells and peripheral blood mononuclear cells from cancer patients[J]. Eur Cytokine Netw, 1998, 9(2): 155-159.
[31] Kurokawa H, Yamashita M, Yamashita Y, et al.Estimation of tumor necrosis factor-alpha in the diagnosis, the prognosis and the treatment follow-up of oral squamous cell carcinoma[J]. Fukuoka Igaku Zasshi, 1998, 89(11): 312-320.
[32] Nakano Y, Kobayashi W, Sugai S, et al.Expression of tumor necrosis factor-alpha and interleukin-6 in oral squamous cell carcinoma[J]. Jpn J Cancer Res, 1999, 90(8): 858-866.
[33] Deepthi G, Nandan SRK, Kulkarni PG, et al.Salivary tumour necrosis factor-α as a biomarker in oral leukoplakia and oral squamous cell carcinoma[J]. Asian Pac J Cancer Prev, 2019, 20(7): 2087-2093.
[34] Skrinjar I, Brailo V, Vidovic-Juras D, et al.Evaluation of pretreatment serum interleukin-6 and tumour necrosis factor alpha as a potential biomarker for recurrence in patients with oral squamous cell carcinoma[J]. Med Oral Patol Oral Cir Bucal, 2015, 20(4): e402-e407.
[35] Krishnan R, Thayalan DK, Padmanaban R, et al.Association of serum and salivary tumor necrosis factor-α with histological grading in oral cancer and its role in differentiating premalignant and malignant oral disease[J]. Asian Pac J Cancer Prev, 2014, 15(17): 7141-7148.
[36] Wang Z, Zhang J, Wen Y, et al.Bupivacaine inhibits the malignant biological behavior of oral squamous cell carcinoma cells by inhibiting the activation of ERK1/2 and STAT3[J]. Ann Transl Med, 2021, 9(10): 839-851.
[37] Aotsuka A, Matsumoto Y, Arimoto T, et al.Interleukin-17 is associated with expression of programmed cell death 1 ligand 1 in ovarian carcinoma[J]. Cancer Sci, 2019, 110(10): 3068-3078.
[38] Dikova V, Jantus-Lewintre E, Bagan J, et al.Potential non-invasive biomarkers for early diagnosis of oral squamous cell carcinoma[J]. J Clin Med, 2021,10(8): 1658-1673.
[39] Wang S, Sun M, Gu C, et al.Expression of CD163, interleukin-10, and interferon-gamma in oral squamous cell carcinoma: mutual relationships and prognostic implications[J]. Eur J Oral Sci, 2014, 122(3): 202-209.
[40] Belting L, Hömberg N, Przewoznik M, et al.Critical role of the NKG2D receptor for NK cell-mediated control and immune escape of B-cell lymphoma[J]. Eur J Immunol, 2015, 45(9): 2593-2601.
[41] 王艳, 陈璐. LEP、TNF-α、CEA、CRP和IL-6在结核病与恶性肿瘤中的鉴别诊断价值[J]. 中国实验诊断学, 2014, 18(12): 1993-1996.
[42] 边勤疆, 多力昆·吾甫尔. 5种肿瘤标志物联合检测在口腔鳞状细胞癌中的诊断价值[J]. 现代肿瘤医学, 2020, 28(19): 3330-3333.