ANALYTICAL STUDY OF SALIVARY MMP-12 EXPRESSION IN ORAL SUBMUCOUS FIBROSIS
AbstractBackground: Oral submucous fibrosis (OSF) is majorly a pathology pertaining to Asian population, reported most in Pakistan, India, Nepal, Bangladesh, and Taiwan. Equilibrium existing between Matrix metalloproteinases (MMP) & tissue inhibitors of matrix metalloproteinases is imperative for the normal integrity of connective tissues. However, this mechanism is disturbed in the presence of OSF, resulting in an increase in the extracellular matrix. Methods: It is an analytical study including two groups with a total of 60 participants. The first group consists of 30 healthy participants and the other group consists of 30 patients presenting with oral submucous fibrosis. Collected samples of saliva were stored at -80 °C after centrifugation. For ELISA investigation, the procedure was performed as per manufacturer’s instruction. Salivary matrix metalloproteinases- 12 concentration was estimated with the help of a standard curve. Data was analysed using SPSS 23. Mann Whitney test was applied to determine the difference existing in Matrix metalloproteinases- 12 levels between healthy and Oral submucous fibrosis participants. p-value <0.05 was contemplated as significant. Results: Statistical investigation indicated significant difference in Matrix metalloproteinases- 12 levels between Oral submucous fibrosis and healthy group (p<0.05). Saliva samples obtained from oral submucous fibrosis patients demonstrated raised concentrations of Matrix metalloproteinases- 12 as compared to healthy participants. Conclusion: Our study demonstrates significant upsurge in Matrix metalloproteinases- 12 expression in samples of saliva obtained from oral submucous fibrosis patients as compared to healthy individuals. Therefore, salivary Matrix metalloproteinases- 12 could serve as a useful diagnostic marker for OSF.
1. Hosein M, Mohiuddin S, Fatima N. Association between grading of oral submucous fibrosis with frequency and consumption of areca nut and its derivatives in a wide age group: A multi-centric cross sectional study from Karachi, Pakistan. J Cancer Prev 2015;20(3):216–22.
Shaikh AH, Ahmed S, Siddique S, Iqbal N, Hasan SMU, Zaidi SJA, et al. Oral submucous fibrosis. Prof Med J 2019;26(02):275–81.
Holla VA, Chatra L, Shenai P, Shetty D, Baliga A. A study to analyze different patterns of quid usage among subjects with oral submucous fibrosis in Mangalore population. Adv Med 2016;2016:6124059.
Gupta S, Singh R, Gupta O, Tripathi A. Prevalence of oral cancer and pre-cancerous lesions and the association with numerous risk factors in North India: A hospital based study. Natl J Maxillofac Surg 2014;5(2):142–8.
Mathew P, Austin RD, Varghese SS, Manoj Kumar A. Role of areca nut and its commercial products in oral submucous fibrosis-a review. J Adv Med Dent Sci Res 2014;2(3):192–200.
Saleem Z, Abbas SA, Nadeem F, Majeed MM. The habits and reasons of delayed presentation of patients with oral cancer at a tertiary care hospital of a third world country. Pak J Public Health 2018;8(3):165–9.
IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Betel-quid and areca-nut chewing and some areca-nut derived nitrosamines. IARC Monogr Eval Carcinog Risks Hum 2004;85:1–334.
Wollina U, Verma SB, Ali FM, Patil K. Oral submucous fibrosis: an update. Clin Cosmet Investig Dermatol 2015;8:193–204.
Haider S, Merchant A, Fikree F, Rahbar M. Clinical and functional staging of oral submucous fibrosis. Br J Oral Maxillofac Surg 2000;38(1):12–5.
Haque M, Meghji S, Khitab U, Harris M. Oral submucous fibrosis patients have altered levels of cytokine production. J Oral Pathol Med 2000;29(3):123–8.
Hsu HJ, Chang KL, Yang YH, Shieh TY. The effects of arecoline on the release of cytokines using cultured peripheral blood mononuclear cells from patients with oral mucous diseases. Kaohsiung J Med Sci 2001;17(4):175–82.
Avinash Tejasvi ML, Bangi BB, Geetha P, Anulekha Avinash CK, Chittaranjan B, Bhayya H, et al. Estimation of serum superoxide dismutase and serum malondialdehyde in oral submucous fibrosis: A clinical and biochemical study. J Cancer Res Ther 2014;10(3):722–5.
Jani YV, Chaudhary AR, Dudhia BB, Bhatia PV, Soni NC, Patel PS. Evaluation of role of trace elements in oral submucous fibrosis patients: A study on Gujarati population. J Oral Maxillofac Pathol 2017;21(3):455.
Sachdev PK, Freeland-Graves J, Beretvas SN, Sanjeevi N. Zinc, copper, and iron in oral submucous fibrosis: A meta-analysis. Int J Dent 2018;2018:3472087.
Peng Q, Li H, Chen J, Wang Y, Tang Z. Oral submucous fibrosis in Asian countries. J Oral Pathol Med 2020;49(4):294–304.
Tilakaratne WM, Ekanayaka RP, Warnakulasuriya S. Oral submucous fibrosis: a historical perspective and a review on etiology and pathogenesis. Oral Surg Oral Med Oral Pathol Oral Radiol 2016;122(2):178–91.
Passi D, Bhanot P, Kacker D, Chahal D, Atri M, Panwar Y. Oral submucous fibrosis: Newer proposed classification with critical updates in pathogenesis and management strategies. Natl J Maxillofac Surg 2017;8(2):89–94.
Chaudhary AK, Pandya S, Mehrotra R, Singh M, Singh M. Role of functional polymorphism of matrix metalloproteinase-2 (-1306 C/T and -168 G/T) and MMP-9 (-1562 C/T) promoter in oral submucous fibrosis and head and neck squamous cell carcinoma in an Indian population. Biomarkers 2011;16(7):577–86.
Rajalalitha P, Vali S. Molecular pathogenesis of oral submucous fibrosis–a collagen metabolic disorder. J Oral Pathol Med 2005;34(6):321–8.
Singh P, Rai A, Dohare R, Arora S, Ali S, Parveen S, et al. Network‑based identification of signature genes KLF6 and SPOCK1 associated with oral submucous fibrosis. Mol Clin Oncol 2020;12(4):299–310.
Ray JG, Ranganathan K, Chattopadhyay A. Malignant transformation of oral submucous fibrosis: overview of histopathological aspects. Oral Surg Oral Med Oral Pathol Oral Radiol 2016;122(2):200–9.
Warnakulasuriya S, Tilakaratne W, Kerr A. Oral Submucous Fibrosis. Contemporary Oral Oncology: Springer, 2017; p.329–53.
Mishra G, Ranganathan K. Matrix metalloproteinase-1 expression in oral submucous fibrosis: An immunohistochemical study. Indian J Dent Res 2010;21(3):320–5.
Chattopadhyay A, Ray JG. Molecular Pathology of Malignant Transformation of Oral Submucous Fibrosis. J Environ Pathol Toxicol Oncol 2016;35(3):193–205.
Rajendran R, Rajeesh MP, Shaikh S, Shanthi, Pillai MR. Expression of matrix metalloproteinases (MMP-1, MMP-2 and MMP-9) and their inhibitors (TIMP-1 and TIMP-2) in oral submucous fibrosis. Indian J Dent Res 2006;17(4):161–6.
Pitiyage GN, Lim KP, Gemenitzidis E, Teh MT, Waseem A, Prime SS, et al. Increased secretion of tissue inhibitors of metalloproteinases 1 and 2 (TIMPs -1 and -2) in fibroblasts are early indictors of oral sub-mucous fibrosis and ageing. J Oral Pathol Med 2012;41(6):454–62.
Shrestha A, Carnelio S. Evaluation of Matrix Metalloproteinases-2 (MMP-2) and Tissue Inhibitors of Metalloproteinases-2 (TIMP-2) in Oral Submucous Fibrosis and Their Correlation With Disease Severity. Kathmandu Univ Med J (KMUJ) 2013;11(4):274–81.
Ekanayaka RP, Tilakaratne WM. Oral submucous fibrosis: review on mechanisms of malignant transformation. Oral Surg Oral Med Oral Pathol Oral Rad 2016;122(2):192–9.
Chang YC, Yang SF, Tai KW, Chou MY, Hsieh YS. Increased tissue inhibitor of metalloproteinase-1 expression and inhibition of gelatinase A activity in buccal mucosal fibroblasts by arecoline as possible mechanisms for oral submucous fibrosis. Oral Oncol 2002;38(2):195–200.