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Salivary level of interleukin-8 in oral precancer and oral squamous cell carcinoma

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Abstract

Background

Interleukin 8 (IL-8) is a pro-angiogenic, pro-inflammatory mediator that belongs to the family of chemokines. Due to its pro-angiogenic characteristic, it may play a vital role in tumour angiogenesis and progression.

Objectives

This study was designed to estimate the levels of salivary IL-8 in oral precancer and oral squamous cell carcinoma (OSCC) patients and compare them with healthy controls. The aim was to evaluate its efficacy as a potential biomarker for these diseases.

Materials and methods

Each group comprised 25 individuals. The salivary IL-8 levels were determined by enzyme-linked immunosorbent assay.

Results

The levels of salivary IL-8 were found to be significantly elevated in patients with OSCC as compared to the precancer group (p < 0.0001) and healthy controls (p < 0.0001). However, the difference in salivary IL-8 concentrations among the precancer group and controls was statistically non-significant (p = 0.738).

Conclusions

Our results suggested that salivary IL-8 can be utilised as a potential biomarker for OSCC. Salivary IL-8 was found to be non-conclusive for oral premalignancy in this preliminary study. Hence, its possible role in transition from premalignancy to malignancy needs further research with larger sample sizes.

Clinical relevance

Saliva as a diagnostic biofluid offers a number of advantages over blood-based testing. The role of IL-8 in oral cancer if validated further by future research can provide an easy diagnostic test as well as a prognostic indicator for patients undergoing treatment. Therefore, if it’s role in tumourigenesis can be sufficiently assessed, it could open up new avenues to find out novel treatment modalities for oral cancer.

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Abbreviations

IL-8:

Interleukin 8

OSCC:

Oral squamous cell carcinoma

HNSCC:

Head and neck squamous cell carcinoma.

OSF:

Oral submucous fibrosis

MDSCC:

Moderately differentiated squamous cell carcinoma

WDSCC:

Well-differentiated squamous cell carcinoma

References

  1. Mehrotra R, Yadav S (2006) Oral squamous cell carcinoma: etiology, pathogenesis and prognostic value of genomic alterations. Indian J Cancer 43:60–66

    Article  PubMed  Google Scholar 

  2. Khanna SS, Karjodkar FR (2006) Circulating immune complexes and trace elements (copper, iron and selenium) as markers in oral precancer and cancer: a randomised, controlled clinical trial. Head Face Med 2:33

    Article  PubMed  Google Scholar 

  3. Shafer WG, Levy BM, Hine MK, Rajendran R, Sivapathasundharam B (2006) Shafer’s textbook of oral pathology. Elsevier, New Delhi

    Google Scholar 

  4. Oliveira LR, Ribeiro-Silva A (2011) Prognostic significance of immunohistochemical biomarkers in oral squamous cell carcinoma. Int J Oral Maxillofac Surg 40:298–307

    Article  PubMed  Google Scholar 

  5. Chang YC, Nieh S, Chen S-F, Jao S-W, Lin Y-L, Fu E (2010) Invasive pattern grading score designed as an independent prognostic indicator in oral squamous cell carcinoma. Histopathology 57:295–303

    Article  PubMed  Google Scholar 

  6. Nagler RM, Barak M, Ben-Aryeh H, Peled M, Filatov M, Laufer D (1999) Early diagnostic and treatment monitoring role of Cyfra 21-1 and TPS in oral squamous cell carcinoma. Cancer 35:1018–1025

    Article  Google Scholar 

  7. Bhatavdekar JM, Patel DD, Vora HH, Balar DB (1993) Circulating markers and growth factors as prognosticators in men with advanced tongue cancer. Tumour Biol 14:55–58

    Article  PubMed  Google Scholar 

  8. Bhatavdekar JM, Patel DD, Vora HH, Balar DB (1993) Circulating prolactin and TPS in monitoring the clinical course of male patients with metastatic tongue cancer: a preliminary study. Anticancer Res 13:237–240

    PubMed  Google Scholar 

  9. Krimmel M, Hoffmann J, Krimmel C, Cornelius CP, Schwenzer N (1998) Relevance of SCC-Ag, CEA, CA 19.9, and CA125 for diagnosis and follow-up in oral cancer. J Craniomaxillofac Surg 26:243–248

    Article  PubMed  Google Scholar 

  10. Kuo WR, Lee KW, Ho KY, Tsai SM, Chiang FY, Juan KH (1999) Tissue polypeptide antigen, carcinoembryonic antigen, carbohydrate antigen, and CA125 levels as tumor markers in squamous cell carcinoma of the head and neck. Kaohsiung J Med Sci 15:152–158

    PubMed  Google Scholar 

  11. Hoffmann J, Munz A, Krimmel M, Alfter G (1998) Intraoperative and postoperative kinetics of serum tumor markers in patients with oral carcinoma. J Oral Maxillofac Surg 56:1390–1393

    Article  PubMed  Google Scholar 

  12. Groschl M, Kohler H, Topf HG, Rupprecht T, Rauh M (2008) Evaluation of saliva collection devices for the analysis of steroids, peptides and therapeutic drugs. J Pharm Biomed Anal 47:478–486

    Article  PubMed  Google Scholar 

  13. Zimmermann BG, Wong DT (2008) Salivary mRNA targets for cancer diagnostics. Oral Oncol 44:425–429

    Article  PubMed  Google Scholar 

  14. Young MRI, Wright MA, Lozano Y, Prechel MM, Benefield J, Leonetti JP, Collins SL et al (1997) Increased recurrence and metastasis in patients whose primary head and neck squamous cell carcinomas secreted granulocyte–macrophage colony-stimulating factor and contained CD34+ natural suppressor cells. Int J Cancer 74:69–74

    Article  PubMed  Google Scholar 

  15. Gleich LL, Biddinger PW, Duperier FD, Gluckman JL (1997) Tumor angiogenesis as a prognostic indicator in T2–T4 oral cavity squamous cell carcinoma: a clinical–pathologic correlation. Head Neck 19:276–280

    Article  PubMed  Google Scholar 

  16. Pak AS, Wright MA, Matthews JP, Collins SL, Petruzzelli GJ, Young MR (1995) Mechanisms of immune suppression in patients with head and neck cancer: presence of CD34(+) cells which suppress immune functions within cancers that secrete granulocyte–macrophage colony-stimulating factor. Clin Cancer Res 1:95–103

    PubMed  Google Scholar 

  17. Smith CW, Chen Z, Dong G, Loukinova E, Pegram MY, Figueroa LN, Waes CV (1998) The host environment promotes the development of primary and metastatic squamous cell carcinomas that constitutively express proinflammatory cytokines IL-1 α, IL-6, GM-CSF, and KC. Clin Exp Metastasis 16:655–664

    Article  PubMed  Google Scholar 

  18. Rhodus NL, Ho V, Miller CS, Myers S, Ondrey F (2005) NF-kappa B dependent cytokine levels in saliva of patients with oral preneoplastic lesions and oral squamous cell carcinoma. Cancer Detect Prev 29:42–45

    Article  PubMed  Google Scholar 

  19. Liao PH, Chang YC, Huang MF, Tai KW, Chou MY (2000) Mutation of p53 gene codon 63 in saliva as a molecular marker for oral squamous cell carcinomas. Oral Oncol 36:272–276

    Article  PubMed  Google Scholar 

  20. Zhong LP, Chen GF, Xu ZF, Zhang X, Ping FY, Zhao SF (2005) Detection of telomerase activity in saliva from oral squamous cell carcinoma patient. Int J Oral Maxillofac Surg 34:566–570

    Article  PubMed  Google Scholar 

  21. Balicki R, Grabowskaa SZ, Citkob A (2005) Salivary epidermal growth factor in oral cavity cancer. Oral Oncol 41:48–55

    Article  PubMed  Google Scholar 

  22. Nagler R, Bahar G, Shpitzer T, Feinmesser R (2006) Concomitant analysis of salivary tumor markers—a new diagnostic tool for oral cancer. Clin Cancer Res 12:3979–3984

    Article  PubMed  Google Scholar 

  23. Pickering V, Jordan RCK, Schmidt BL (2007) Elevated salivary endothelin levels in oral cancer patients—a pilot study. Oral Oncol 43:37–41

    Article  PubMed  Google Scholar 

  24. Rhodus NL, Cheng B, Myers S, Miller L, Ho V, Ondrey F (2005) The feasibility of monitoring NF-κB associated cytokines: TNF-α, IL-1α, IL-6, and IL-8 in whole saliva for the malignant transformation of oral lichen planus. Mol Carcinog 44:77–82

    Article  PubMed  Google Scholar 

  25. Chaiyarit P, Ultrawichian A, Leelayuwat C, Vatanasapt P, Chcnchareonsook N, Samson MH, Giraud AS (2011) Investigation of trefoil factor expression in saliva and oral mucosal tissues of patients with oral squamous cell carcinoma. Clin Oral Investig. doi:10.1007/s00784-011-0667-z

  26. Rai B, Kaur J, Jacobs R, Anand SC (2011) Adenosine deaminase in saliva as a diagnostic marker of squamous cell carcinoma. Clin Oral Investig 15:347–349

    Article  PubMed  Google Scholar 

  27. Belperio JA, Keane MP, Arenberg DA, Addison CL, Ehlert JE, Burdick MD, Strieter RM (2000) CXC chemokines in angiogenesis. J Leukoc Biol 68:1–6

    PubMed  Google Scholar 

  28. Richards BL, Eisma RJ, Spiro JD, Lindquist RL, Kreutzer DL (1997) Co-expression of interleukin-8 receptors in head and neck squamous cell carcinoma. Am J Surg 174:507–512

    Article  PubMed  Google Scholar 

  29. Greenberg MS, Glick M, Ship JA (2008) Burkets oral medicine. BC Decker, Ontario

    Google Scholar 

  30. Greenberg MS, Glick M (2003) Burket’s oral medicine diagnosis and treatment. BC Decker, Ontario

    Google Scholar 

  31. Navazesh M, Christensen CM (1982) A comparison of whole mouth resting and stimulated salivary measurement procedures. J Dent Res 61:1158–1162

    Article  PubMed  Google Scholar 

  32. Balkwill F (2004) Cancer and the chemokine network. Nat Rev Cancer 4:540–545

    Article  PubMed  Google Scholar 

  33. Strieter RM, Burdick MD, Mestas J, Gomperts B, Keane MP, Belperio JA (2006) Cancer CXC chemokine networks and tumour angiogenesis. Eur J Cancer 42:768–778

    Article  PubMed  Google Scholar 

  34. Yeudall WA, Miyazaki H (2007) Chemokines and squamous cancer of the head and neck: targets for therapeutic intervention. Expert Rev Anticancer Ther 7:351–360

    Article  PubMed  Google Scholar 

  35. Bailey C, Negus R, Morris A, Ziprin P, Goldin R, Allavena P et al (2007) Chemokine expression is associated with the accumulation of tumour associated macrophages (TAMs) and progression in human colorectal cancer. Clin Exp Metastasis 24:121–130

    Article  PubMed  Google Scholar 

  36. Varney ML, Johansson SL, Singh RK (2006) Distinct expression of CXCL8 and its receptors CXCR1 and CXCR2 and their association with vessel density and aggressiveness in malignant melanoma. Am J Clin Pathol 125:209–216

    PubMed  Google Scholar 

  37. Brat DJ, Bellail AC, Van Meir EG (2005) The role of interleukin-8 and its receptors in gliomagenesis and tumoral angiogenesis. Neuro Oncol 7:122–133

    Article  PubMed  Google Scholar 

  38. Son DS, Parl AK, Rice VM, Khabele D (2007) Keratinocyte chemoattractant (kc)/human growth-regulated oncogene (gro) chemokines and pro-inflammatory chemokine networks in mouse and human ovarian epithelial cancer cells. Cancer Biol Ther 6:1302–1312

    Article  PubMed  Google Scholar 

  39. Mandel ID (1993) Salivary diagnosis: more than a lick and a promise. J Am Dent Assoc 124:85–87

    PubMed  Google Scholar 

  40. Ramsey PS, Andrews WW (2003) Biochemical predictors of preterm labor: fetal fibronectin and salivary estriol. Clin Perinatol 30:701–733

    Article  PubMed  Google Scholar 

  41. Hodinka R, Nagashunmugam T, Malamud D (1998) Detection of human immunodeficiency virus antibodies in oral fluids. Clin Diagn Lab Immunol 5:419–426

    PubMed  Google Scholar 

  42. Mortimer PP, Parry JV (1994) Detection of antibody to HIV in saliva: a brief review. Clin Diagn Virol 2:231–243

    Article  PubMed  Google Scholar 

  43. Mager DL (2005) The salivary microbiota as a diagnostic indicator of oral cancer: a descriptive, non-randomized study of cancer-free and oral squamous cell carcinoma subjects. J Transl Med 3:27

    Article  PubMed  Google Scholar 

  44. Rosas SL, Koch W, da Costa Carvalho MG (2001) Promoter hypermethylation patterns of p16, O6-methylguanine-DNAmethyl-transferase, and death-associated protein kinase in tumors and saliva of head and neck cancer patients. Cancer Res 61:939–942

    PubMed  Google Scholar 

  45. Jiang WW, Masayesva B, Zahurak M et al (2005) Increased mitochondrial DNA content in saliva associated with head and neck cancer. Clin Cancer Res 11:2486–2491

    Article  PubMed  Google Scholar 

  46. Miller SM (1994) Saliva testing: a nontraditional diagnostic tool. Clin Lab Sci 7:39–44

    PubMed  Google Scholar 

  47. Wong DT (2006) Salivary diagnostics powered by nanotechnologies, proteomics and genomics. J Am Dent Assoc 137:313–321

    PubMed  Google Scholar 

  48. Cohen RF, Contrino J, Spiro JD, Mann EA, Chen LL, Kreutzer DL (1995) Interleukin-8 expression by head and neck squamous cell carcinoma. Arch Otolaryngol Head Neck Surg 121:202–209

    Article  PubMed  Google Scholar 

  49. Chen Z, Malhotra PS, Thomas GS, Ondrey FG, Duffey DC, Smith CW et al (1999) Expression of proinflammatory and proangiogenic cytokines in patients with head and neck cancer. Clin Cancer Res 5:1369–1379

    PubMed  Google Scholar 

  50. St John MAR, Li Y, Zhou X, Denny P, Ho CM, Montemagno C et al (2004) Interleukin 6 and interleukin 8 as potential biomarkers for oral cavity and oropharyngeal squamous cell carcinoma. Arch Otolaryngol Head Neck Surg 130:929–935

    Article  PubMed  Google Scholar 

  51. Katakura A, Kamiyama I, Takano N, Shibahara T, Muramatsu T, Ishihara K et al (2007) Comparison of salivary cytokine levels in oral cancer patients and healthy subjects. Bull Tokyo Dent Coll 48:199–203

    Article  PubMed  Google Scholar 

  52. SahebJamee M, Eslami M, Moghadam FA, Sarafnejad A (2008) Salivary concentration of TNFα, IL1α, IL6, and IL8 in oral squamous cell carcinoma. Med Oral Patol Oral Cir Bucal 13:292–295

    Google Scholar 

  53. Khan A, Farah CS, Savage NW, Walsh LJ, Harbrow DJ, Sugerman PB (2003) Th1 cytokines in oral lichen planus. J Oral Pathol Med 32:77–83

    Article  PubMed  Google Scholar 

  54. Haque MF, Meghji S, Khitab S, Harris M (2000) Oral submucous fibrosis patients have altered levels of cytokine production. J Oral Pathol Med 20:123–128

    Article  Google Scholar 

  55. Brailo V, Boras VV, Arambasin AC, Alajbeg IZ, Milenovic A, Lukac J (2006) The significance of salivary interleukin 6 and tumor necrosis factor alpha in patients with oral leukoplakia. Oral Oncol 42:370–373

    Article  PubMed  Google Scholar 

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Conflict of interest statement

None declared.

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Authors and Affiliations

  1. Department of Oral Medicine and Radiology, Government Dental College and Hospital, 1135-Kaushal Bhavan, Central Avenue, Gandhibagh, Nagpur, Maharashtra, 440032, India

    Silky Rajesh Punyani

  2. Department of Oral Medicine and Radiology, VSPM’s Dental College and Research Centre, Nagpur, Maharashtra, India

    Ramhari Shankarrao Sathawane

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  1. Silky Rajesh Punyani
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  2. Ramhari Shankarrao Sathawane
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Correspondence to Silky Rajesh Punyani.

Additional information

Silky Rajesh Punyani and Ramhari Shankarrao Sathawane contributed equally to this work.

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Punyani, S.R., Sathawane, R.S. Salivary level of interleukin-8 in oral precancer and oral squamous cell carcinoma. Clin Oral Invest 17, 517–524 (2013). https://doi.org/10.1007/s00784-012-0723-3

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