Evaluation of salivary biomarkers in patients with oral epithelial dysplasia: A systematic review

Document Type : Review Article(s)

Authors

1 Assistant Professor, Department of Oral Medicine, School of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran

2 Associate Professor, Department of Restorative Dentistry, School of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran

3 Assistant Professor, Department of Community Oral Health, School of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran

4 Liver and Gastrointestinal Disease Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

5 Student of Dentistry, Department of Oral Medicine, School of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran

Abstract

BACKGROUND AND AIM: Early detection of premalignant oral lesions, especially in high-risk patients, is important to prevent mortality. Dysplastic changes are one of the elements of premalignant lesions which can be perceived in histopathologic examinations. The use of saliva is a promising method for diagnosing epithelial dysplasia, because it is non-invasive and easy to collect. This review evaluated the salivary biomarkers in patients with oral epithelial dysplasia (OED).
METHODS: In this systematic review study, all English articles were searched in the PubMed, Cochrane Library, Web of Science, and Scopus databases until February 2021. The searches were done using the Medical Subject Heading (MeSH) terms and free keywords. Textual data were analyzed manually and significant differences in salivary levels of biomarkers between patients with dysplastic lesions and healthy controls were reported and analyzed.
RESULTS: Originally, 1726 articles were found, of which 17 case-control articles were selected according to the inclusion/exclusion criteria. In 85% of studies, proinflammatory cytokine levels were significantly increased in the groups with epithelial dysplasia compared to the control groups. Tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1α showed an increase in all OED cases, but IL-1β showed no significant difference between epithelial dysplasia and control groups. Salivary levels of 14 types of micro-ribonucleic acid (miRNA) were studied, the most important of which were miRNAs 21 and 31, indicating a significant increase in the epithelial dysplasia groups compared to the control groups.
CONCLUSION: Based on the results of this systematic review, evaluation of salivary cytokines (TNF-α, IL-6, and IL-1α) and miRNAs 21 and 31 may be a non-invasive method in the early detection and prognosis of epithelial dysplasia and may also be useful in developing new prevention and treatment strategies.

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Main Subjects


  1. Napier SS, Speight PM. Natural history of potentially malignant oral lesions and conditions: an overview of the literature. J Oral Pathol Med 2008; 37(1): 1-10.
  2. van der Waal I. Potentially malignant disorders of the oral and oropharyngeal mucosa; terminology, classification and present concepts of management. Oral Oncol 2009; 45(4-5): 317-23.
  3. Huber MA. A review of premalignant oral conditions. Tex Dent J 2006; 123(6): 502-9.
  4. Scully C. Oncogenes, onco-suppressors, carcinogenesis and oral cancer. Br Dent J 1992; 173(2): 53-9.
  5. Yang EC, Tan MT, Schwarz RA, Richards-Kortum RR, Gillenwater AM, Vigneswaran N. Noninvasive diagnostic adjuncts for the evaluation of potentially premalignant oral epithelial lesions: Current limitations and future directions. Oral Surg Oral Med Oral Pathol Oral Radiol 2018; 125(6): 670-81.
  6. Ilyin SE, Belkowski SM, Plata-Salaman CR. Biomarker discovery and validation: technologies and integrative approaches. Trends Biotechnol 2004; 22(8): 411-6.
  7. Silberring J, Ciborowski P. Biomarker discovery and clinical proteomics. Trends Analyt Chem 2010; 29(2): 128.
  8. Cristaldi M, Mauceri R, Di Fede O, Giuliana G, Campisi G, Panzarella V. Salivary biomarkers for oral squamous cell carcinoma diagnosis and follow-up: current status and perspectives. Front Physiol 2019; 10: 1476.
  9. Maheswari TNU, Venugopal A, Sureshbabu NM, Ramani P. Salivary micro RNA as a potential biomarker in oral potentially malignant disorders: A systematic review. Ci Ji Yi Xue Za Zhi 2018; 30(2): 55-60.
  10. Roi A, Roi CI, Negrutiu ML, Rivis M, Sinescu C, Rusu LC. The challenges of OSCC Diagnosis: Salivary cytokines as potential biomarkers. J Clin Med 2020; 9(9): 2866.
  11. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 2009; 6(7): e1000097.
  12. Uma Maheswari TN, Nivedhitha MS, Ramani P. Expression profile of salivary micro RNA-21 and 31 in oral potentially malignant disorders. Braz Oral Res 2020; 34: e002.
  13. Mehdipour M, Shahidi M, Manifar S, Jafari S, Mashhadi AF, Barati M, et al. Diagnostic and prognostic relevance of salivary microRNA-21, -125a, -31 and -200a levels in patients with oral lichen planus - a short report. Cell Oncol (Dordr) 2018; 41(3): 329-34.
  14. Shahidi M, Jafari S, Barati M, Mahdipour M, Gholami MS. Predictive value of salivary microRNA-320a, vascular endothelial growth factor receptor 2, CRP and IL-6 in Oral lichen planus progression. Inflammopharmacology 2017. [Epub ahead of print].
  15. Hung KF, Liu CJ, Chiu PC, Lin JS, Chang KW, Shih WY, et al. MicroRNA-31 upregulation predicts increased risk of progression of oral potentially malignant disorder. Oral Oncol 2016; 53: 42-7.
  16. Zahran F, Ghalwash D, Shaker O, Al-Johani K, Scully C. Salivary microRNAs in oral cancer. Oral Dis 2015; 21(6): 739-47.
  17. Yang Y, Li YX, Yang X, Jiang L, Zhou ZJ, Zhu YQ. Progress risk assessment of oral premalignant lesions with saliva miRNA analysis. BMC Cancer 2013; 13: 129.
  18. Babiuch K, Kusnierz-Cabala B, Kesek B, Okon K, Darczuk D, Chomyszyn-Gajewska M. Evaluation of proinflammatory, NF-kappaB dependent cytokines: IL-1alpha, IL-6, IL-8, and TNF-alpha in tissue specimens and saliva of patients with oral squamous cell carcinoma and oral potentially malignant disorders. J Clin Med 2020; 9(3): 867.
  19. G D, Nandan SRK, Kulkarni PG. Salivary tumour necrosis factor-alpha as a biomarker in oral leukoplakia and oral squamous cell carcinoma. Asian Pac J Cancer Prev 2019; 20(7): 2087-93.
  20. Ameena M, Rathy R. Evaluation of tumor necrosis factor: Alpha in the saliva of oral cancer, leukoplakia, and healthy controls - A comparative study. J Int Oral Health 2019; 11(2): 92-9.
  21. Michailidou E, Tzimagiorgis G, Chatzopoulou F, Vahtsevanos K, Antoniadis K, Kouidou S, et al. Salivary mRNA markers having the potential to detect oral squamous cell carcinoma segregated from oral leukoplakia with dysplasia. Cancer Epidemiol 2016; 43: 112-8.
  22. Gleber-Netto FO, Yakob M, Li F, Feng Z, Dai J, Kao HK, et al. Salivary biomarkers for detection of oral squamous cell carcinoma in a Taiwanese population. Clin Cancer Res 2016; 22(13): 3340-7.
  23. Dineshkumar T, Ashwini BK, Rameshkumar A, Rajashree P, Ramya R, Rajkumar K. Salivary and serum interleukin-6 levels in oral premalignant disorders and squamous cell carcinoma: diagnostic value and clinicopathologic correlations. Asian Pac J Cancer Prev 2016; 17(11): 4899-906.
  24. Kaur J, Jacobs R. Proinflammatory cytokine levels in oral lichen planus, oral leukoplakia, and oral submucous fibrosis. J Korean Assoc Oral Maxillofac Surg 2015; 41(4): 171-5.
  25. Krishnan R, Thayalan DK, Padmanaban R, Ramadas R, Annasamy RK, Anandan N. Association of serum and salivary tumor necrosis factor-alpha with histological grading in oral cancer and its role in differentiating premalignant and malignant oral disease. Asian Pac J Cancer Prev 2014; 15(17): 7141-8.
  26. Juretic M, Cerovic R, Belusic-Gobic M, Brekalo P, I, Kqiku L, Spalj S, et al. Salivary levels of TNF-alpha and IL-6 in patients with oral premalignant and malignant lesions. Folia Biol (Praha) 2013; 59(2): 99-102.
  27. Rhodus NL, Cheng B, Myers S, Miller L, Ho V, Ondrey F. The feasibility of monitoring NF-kappaB associated cytokines: TNF-alpha, IL-1alpha, IL-6, and IL-8 in whole saliva for the malignant transformation of oral lichen planus. Mol Carcinog 2005; 44(2): 77-82.
  28. Rhodus NL, Ho V, Miller CS, Myers S, Ondrey F. NF-kappaB dependent cytokine levels in saliva of patients with oral preneoplastic lesions and oral squamous cell carcinoma. Cancer Detect Prev 2005; 29(1): 42-5.
  29. Herr AE, Hatch AV, Giannobile WV, Throckmorton DJ, Tran HM, Brennan JS, et al. Integrated microfluidic platform for oral diagnostics. Ann N Y Acad Sci 2007; 1098: 362-74.
  30. Kathariya R, Pradeep A. Salivary proteomic biomarkers for oral diseases: A review of literature. Arch Oral Sci Res 2010;1(1):43-9.
  31. Krysan K, Kusko R, Grogan T, O'Hearn J, Reckamp KL, Walser TC, et al. PGE2-driven expression of c-Myc and oncomiR-17-92 contributes to apoptosis resistance in NSCLC. Mol Cancer Res 2014; 12(5): 765-74.
  32. Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA 2008; 105(30): 10513-8.
  33. Ng EK, Chong WW, Jin H, Lam EK, Shin VY, Yu J, et al. Differential expression of microRNAs in plasma of patients with colorectal cancer: A potential marker for colorectal cancer screening. Gut 2009; 58(10): 1375-81.
  34. Danielsson K, Wahlin YB, Gu X, Boldrup L, Nylander K. Altered expression of miR-21, miR-125b, and miR-203 indicates a role for these microRNAs in oral lichen planus. J Oral Pathol Med 2012; 41(1): 90-5.
  35. Madkour G, El-Nahass H, Abd W, Mohamad M. Expression levels of microRNA-21 and microRNA-146a in patients with Oral Lichen Planus. Life Sci J 2012; 9(4): 4666-70.
  36. Tiwari A, Shivananda S, Gopinath KS, Kumar A. MicroRNA-125a reduces proliferation and invasion of oral squamous cell carcinoma cells by targeting estrogen-related receptor alpha: Implications for cancer therapeutics. J Biol Chem 2014; 289(46): 32276-90.
  37. Chen F, Castranova V, Shi X. New insights into the role of nuclear factor-kappaB in cell growth regulation. Am J Pathol 2001; 159(2): 387-97.
  38. Bours V, Bonizzi G, Bentires-Alj M, Bureau F, Piette J, Lekeux P, et al. NF-kappaB activation in response to toxical and therapeutical agents: Role in inflammation and cancer treatment. Toxicology 2000; 153(1-3): 27-38.
  39. Mignogna MD, Fedele S, Lo RL, Lo ML, Bucci E. Immune activation and chronic inflammation as the cause of malignancy in oral lichen planus: is there any evidence? Oral Oncol 2004; 40(2): 120-30.
  40. Chang MC, Wu HL, Lee JJ, Lee PH, Chang HH, Hahn LJ, et al. The induction of prostaglandin E2 production, interleukin-6 production, cell cycle arrest, and cytotoxicity in primary oral keratinocytes and KB cancer cells by areca nut ingredients is differentially regulated by MEK/ERK activation. J Biol Chem 2004; 279(49): 50676-83.
  41. Chapple IL. Time to take periodontitis seriously. BMJ 2014; 348: g2645.
  42. Batchelor P. Is periodontal disease a public health problem? Br Dent J 2014; 217(8): 405-9.