唾液中白细胞介素与口腔癌的关系

doi:10.7518/hxkq.2018.03.018

摘要/Abstract

摘要：

唾液用于疾病的诊断越来越受到重视,由于口腔癌（OCC）发生部位的特点,唾液中白细胞介素（IL）可作为OCC诊断的生物标志物,并与OCC的发生、发展、侵袭、转移密切相关。本文对唾液中IL的检测方法及其与OCC发生、发展的关系等方面的研究进展进行综述。

关键词: 唾液, 白细胞介素, 口腔癌, 生物标志物

Abstract:

Saliva is being attached great importance for its application in illness diagnosis and have more advantage on the diagnose in oral cavity cancer (OCC). Studies have showed that interleukin (IL) in the saliva could be used as a potential biomarker for OCC diagnosis. Moreover, they have a close connection with tumor genesis, invasion, and metastasis in OCC. Therefore, we reviewed research progress on the relationship between salivary interleukins and OCC.

Key words: saliva, interleukin, oral cavity cancer, biomarker

中图分类号:

R739.8

王迪侃, 廖贵清. 唾液中白细胞介素与口腔癌的关系[J]. 华西口腔医学杂志, 2018, 36(3): 325-330.

Dikan Wang, Guiqing Liao. Relationship between interleukins in the saliva and oral cavity cancer[J]. West China Journal of Stomatology, 2018, 36(3): 325-330.

图/表 1

参考文献 48

[1]	Brailo V, Vucicevic-Boras V, Lukac J, et al.Salivary and serum interleukin 1 beta, interleukin 6 and tumor necrosis factor alpha in patients with leukoplakia and oral cancer[J]. Med Oral Patol Oral Cir Bucal, 2012: e10-e15.
[2]	Rajkumar K, Nandhini G, Ramya R, et al.Validation of the diagnostic utility of salivary interleukin 8 in the differen-tiation of potentially malignant oral lesions and oral squa-mous cell carcinoma in a region with high endemicity[J]. Oral Surg Oral Med Oral Pathol Oral Radiol, 2014, 118(3): 309-319.
[3]	Rhodus NL, Ho V, Miller CS, et al.NF-kappaB dependent cytokine levels in saliva of patients with oral preneoplastic lesions and oral squamous cell carcinoma[J]. Cancer Detect Prev, 2005, 29(1): 42-45.
[4]	Liu J, Duan Y.Saliva: a potential media for disease diag-nostics and monitoring[J]. Oral Oncol, 2012, 48(7): 569-577.
[5]	Panneer Selvam N, Sadaksharam J.Salivary interleukin-6 in the detection of oral cancer and precancer[J]. Asia Pac J Clin Oncol, 2015, 11(3): 236-241.
[6]	Arellano-Garcia M, Hu S, Wang J, et al.Multiplexed im-munobead-based assay for detection of oral cancer protein biomarkers in saliva[J]. Oral Dis, 2008, 14(8): 705-712.
[7]	Malhotra R, Patel V, Chikkaveeraiah BV, et al.Ultrasensi-tive detection of cancer biomarkers in the clinic by use of a nanostructured microfluidic array[J]. Anal Chem, 2012, 84(14): 6249-6255.
[8]	Torrente-Rodríguez RM, Campuzano S, Ruiz-Valdepeñas Montiel V, et ala. Electrochemical bioplatforms for the simul-taneous determination of interleukin (IL)-8 mRNA and IL-8 protein oral cancer biomarkers in raw saliva[J]. Biosens Bioelectron, 2016, 77: 543-548.
[9]	Rahnama M, Jastrzębska I, Jamrogiewicz R, et al.IL-1α and IL-1β levels in blood serum and saliva of menopausal women[J]. Endocr Res, 2013, 38(2): 69-76.
[10]	Kamatani T, Shiogama S, Yoshihama Y, et al.Interleukin-1 beta in unstimulated whole saliva is a potential biomarker for oral squamous cell carcinoma[J]. Cytokine, 2013, 64(2): 497-502.
[11]	Öngöz Dede F, Balli U, Bozkurt Doğan Ş, et al.Interleukin-32 levels in gingival crevicular fluid and saliva of patients with chronic periodontitis after periodontal treatment[J]. J Perio-dont Res, 2017, 52(3): 397-407.
[12]	Buduneli N, Özçaka Ö, Nalbantsoy A.Interleukin-33 levels in gingival crevicular fluid, saliva, or plasma do not differ-entiate chronic periodontitis[J]. J Periodontol, 2012, 83(3): 362-368.
[13]	Köseoğlu S, Sağlam M, Pekbağrıyanık T, et al.Level of interleukin-35 in gingival crevicular fluid, saliva, and plasma in periodontal disease and health[J]. J Periodontol, 2015, 86(8): 964-971.
[14]	Simcić D, Pezelj-Ribarić S, Grzić R, et al.Detection of sali-vary interleukin 2 and interleukin 6 in patients with burning mouth syndrome[J]. Mediators Inflamm, 2006, 2006(1): 54632.
[15]	Cogulu D, Onay H, Ozdemir Y, et al.Associations of inter-leukin (IL)-1β, IL-1 receptor antagonist, and IL-10 with dental caries[J]. J Oral Sci, 2015, 57(1): 31-36.
[16]	St John MA, Li Y, Zhou X, et al.Interleukin 6 and interleu-kin 8 as potential biomarkers for oral cavity and oropharyn-geal squamous cell carcinoma[J]. Arch Otolaryngol Head Neck Surg, 2004, 130(8): 929-935.
[17]	Aziz S, Ahmed SS, Ali A, et al.Salivary immunosuppressive cytokines IL-10 and IL-13 are significantly elevated in oral squamous cell carcinoma patients[J]. Cancer Invest, 2015, 33(7): 318-328.
[18]	Brailo V, Vucićević-Boras V, Cekić-Arambasin A, et al.The significance of salivary interleukin 6 and tumor necrosis factor alpha in patients with oral leukoplakia[J]. Oral Oncol, 2006, 42(4): 370-373.
[19]	Punyani SR, Sathawane RS.Salivary level of interleukin-8 in oral precancer and oral squamous cell carcinoma[J]. Clin Oral Investig, 2013, 17(2): 517-524.
[20]	Zhang Y, Liu W, Zhang S, et al.Salivary and serum inter-leukin-18 in patients with oral lichen planus: a study in an ethnic Chinese population[J]. Inflammation, 2012, 35(2): 399-404.
[21]	Lee CH, Syu SH, Liu KJ, et al.Interleukin-1 beta transac-tivates epidermal growth factor receptor via the CXCL1-CXCR2 axis in oral cancer[J]. Oncotarget, 2015, 6(36): 38866-38880.
[22]	Lee CH, Chang JS, Syu SH, et al.IL-1β promotes malignant transformation and tumor aggressiveness in oral cancer[J]. J Cell Physiol, 2015, 230(4): 875-884.
[23]	Sato J, Ohuchi M, Abe K, et al.Correlation between salivary interleukin-6 levels and early locoregional recurrence in patients with oral squamous cell carcinoma: preliminary study[J]. Head Neck, 2013, 35(6): 889-894.
[24]	Gasche JA, Hoffmann J, Boland CR, et al.Interleukin-6 promotes tumorigenesis by altering DNA methylation in oral cancer cells[J]. Int J Cancer, 2011, 129(5): 1053-1063.
[25]	Yu H, Lee H, Herrmann A, et al.Revisiting STAT3 signalling in cancer: new and unexpected biological functions[J]. Nat Rev Cancer, 2014, 14(11): 736-746.
[26]	Huang JS, Yao CJ, Chuang SE, et al.Honokiol inhibits sphere formation and xenograft growth of oral cancer side population cells accompanied with JAK/STAT signaling pathway suppression and apoptosis induction[J]. BMC Can-cer, 2016, 16: 245.
[27]	Teruel A, Romero M, Cacalano NA, et al.Potential contri-bution of naïve immune effectors to oral tumor resistance: role in synergistic induction of VEGF, IL-6, and IL-8 secre-tion[J]. Cancer Immunol Immunother, 2008, 57(3): 359-366.
[28]	Okamoto M, Hiura K, Ohe G, et al.Mechanism for bone invasion of oral cancer cells mediated by interleukin-6 in vitro and in vivo[J]. Cancer, 2000, 89(9): 1966-1975.
[29]	Shinriki S, Jono H, Ueda M, et al.Interleukin-6 signalling regulates vascular endothelial growth factor-C synthesis and lymphangiogenesis in human oral squamous cell carci-noma[J]. J Pathol, 2011, 225(1): 142-150.
[30]	Zarogoulidis P, Katsikogianni F, Tsiouda T, et al.Interleu-kin-8 and interleukin-17 for cancer[J]. Cancer Invest, 2014, 32(5): 197-205.
[31]	Long X, Ye Y, Zhang L, et al.IL-8, a novel messenger to cross-link inflammation and tumor EMT via autocrine and paracrine pathways[J]. Int J Oncol, 2016, 48(1): 5-12.
[32]	Watanabe H, Iwase M, Ohashi M, et al.Role of interleukin-8 secreted from human oral squamous cell carcinoma cell lines[J]. Oral Oncol, 2002, 38(7): 670-679.
[33]	Glogauer JE, Sun CX, Bradley G, et al.Neutrophils increase oral squamous cell carcinoma invasion through an invado-podia-dependent pathway[J]. Cancer Immunol Res, 2015, 3(11): 1218-1226.
[34]	Peng HY, Jiang SS, Hsiao JR, et al.IL-8 induces miR-424-5p expression and modulates SOCS2/STAT5 signaling pathway in oral squamous cell carcinoma[J]. Mol Oncol, 2016, 10(6): 895-909.
[35]	Li X, Fan Q, Li J, et al.MiR-124 down-regulation is critical for cancer associated fibroblasts-enhanced tumor growth of oral carcinoma[J]. Exp Cell Res, 2017, 351(1): 100-108.
[36]	Moore KW, de Waal Malefyt R, Coffman RL, et al. Inter-leukin-10 and the interleukin-10 receptor[J]. Annu Rev Im-munol, 2001, 19: 683-765.
[37]	Zhou X, Su YX, Lao XM, et al.CD19+IL-10+ regulatory B cells affect survival of tongue squamous cell carcinoma patients and induce resting CD4+ T cells to CD4+Foxp3+ regulatory T cells[J]. Oral Oncol, 2016, 53: 27-35.
[38]	Chen CJ, Sung WW, Su TC, et al.High expression of in-terleukin 10 might predict poor prognosis in early stage oral squamous cell carcinoma patients[J]. Clin Chim Acta, 2013, 415: 25-30.
[39]	Chandler SW, Rassekh CH, Rodman SM, et al.Immunohis-tochemical localization of interleukin-10 in human oral and pharyngeal carcinomas[J]. Laryngoscope, 2002, 112(5): 808-815.
[40]	Costa NL, Valadares MC, Souza PP, et al.Tumor-associated macrophages and the profile of inflammatory cytokines in oral squamous cell carcinoma[J]. Oral Oncol, 2013, 49(3): 216-223.
[41]	Hsu HJ, Yang YH, Shieh TY, et al.TGF-β1 and IL-10 single nucleotide polymorphisms as risk factors for oral cancer in Taiwanese[J]. Kaohsiung J Med Sci, 2015, 31(3): 123-129.
[42]	Singh PK, Chandra G, Bogra J, et al.Association of genetic polymorphism in the interleukin-8 gene with risk of oral cancer and its correlation with pain[J]. Biochem Genet, 2016, 54(1): 95-106.
[43]	Vairaktaris E, Yapijakis C, Serefoglou Z, et al.Gene expres-sion polymorphisms of interleukins-1β, -4, -6, -8, -10, and tumor necrosis factors-α, -β: regression analysis of their effect upon oral squamous cell carcinoma[J]. J Cancer Res Clin Oncol, 2008,134(8): 821-832.
[44]	Hwang YS, Lee SK, Park KK, et al.Secretion of IL-6 and IL-8 from lysophosphatidic acid-stimulated oral squamous cell carcinoma promotes osteoclastogenesis and bone resorp-tion[J]. Oral Oncol, 2012, 48(1): 40-48.
[45]	Cvikl B, Lussi A, Moritz A, et al.Sterile-filtered saliva is a strong inducer of IL-6 and IL-8 in oral fibroblasts[J]. Clin Oral Investig, 2015, 19(2): 385-399.
[46]	Sato J, Goto J, Murata T, et al.Changes in saliva interleukin-6 levels in patients with oral squamous cell carcinoma[J]. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 2010, 110
	(3): 330-336.
[47]	Thomas GR, Chen Z, Enamorado I, et al.IL-12- and IL-2-induced tumor regression in a new murine model of oral squamous-cell carcinoma is promoted by expression of the CD80 co-stimulatory molecule and interferon-gamma[J]. Int J Cancer, 2000, 86(3): 368-374.
[48]	Lippitz BE.Cytokine patterns in patients with cancer: a sys-tematic review[J]. Lancet Oncol, 2013, 14(6): e218-e228.

项目	检测方法	正常人群	癌前状态	口腔癌	统计结果
IL-1β	ELISA	354.00±61.51	143.00±54.74	906.00±62.21	*＃^[1]
	Luminex	376.30±576.3	ND	1 013.50±1 221.10	*^[6]
IL-1Ra	Luminex	1 949.2±1 178.0	ND	2 831.7±2 506.4	*^[17]
IL-6	ELISA	9.68±12.838	43.00±52.143	132.88±59.098	*＃ǂ^[5]
	ELISA	4.61±4.42	14.93±16.48	ND	ǂ^[18]
	ELISA	1.4±0.9	70.8±24.3	88.2±43.2	*＃ǂ^[3]
	ELISA	16.00±3.91	18.00±5.19	129.00±66.59	*＃^[1]
IL-8	ELISA	1 580.0±789.0	1 918.2±899.1	3 154.1±1 023.2	*＃ǂ^[3]
	ELISA	210.0±142.3	299.5±158.2	1 718.6±668.3	*＃^[19]
	ELISA	349.6±115.1	650.4±207.3	1 091.7±167.1	*＃ǂ^[2]
	Luminex	947.3±2 036.8	ND	2 834.9±3 385.6	*^[6]
IL-10	Luminex	1.72±1.33	ND	4.45±4.29	*^[17]
IL-13	Luminex	0.23±0.19	ND	0.76±0.57	*^[17]
IL-18	ELISA	12.29±5.11	20.12±5.78	ND	ǂ^[20]