Novel Treatment and Prognostic Value of EMT Biomarkers in Oral Submucous Fibrosis

Objectives: To assess and compare various treatment modalities in OSMF and to evaluate expression of Zeb1, Twist and E-cadherin in oral submucous fibrosis (OSMF) and oral squamous cell carcinoma (OSCC) in Indian population.
Methods: This prospective study was conducted on clinically and histopathologically diagnosed 100 cases of OSMF, 58 cases of OSCC and 20 cases of control. Ethical clearance was obtained and CTRI enrolment was done. Immunohistochemical expression and correlation of molecular markers of Zeb1, Twist and E-cadherin was assessed and compared in OSMF, OSCC and control group. OSMF patients were randomly categorized into 5 treatment groups consisting of Curcumin 300mg twice daily (n=20), Lycopene 8 mg twice daily (n=30), Sesame oil pulling twice daily (n=20), Laser fibrotomy (n=20) and placebo (n=20). After 9 months of follow-up, pre- and post-treatment mouth opening (MO), VAS score, tongue protrusion (TP) and cheek flexibility (CF) were compared. Kruskal-Wallis, Mann-Whitney and Chi-Square statistical tests were applied.

Results: There was significant upregulation of Zeb1 and Twist in OSMF and OSCC (p value <0.05) in comparison to normal mucosa. E-cadherin showed significant upregulation in OSMF and down regulation in OSCC (p value <0.05). There was inverse relationship in expression of Zeb1 and Twist with E-cadherin.
In treatment response of OSMF patients, significant maximum increase in MO (9.4±6.3) and highest improvement in VAS score (5.60±2.94) was observed in sesame oil pulling and curcumin group respectively (p value <0.05).

Conclusions: These can be potential prognostic biomarkers of malignant transformation. Patients with high expression of Zeb1 and Twist and low/negative expression of E-cadherin are at increased risk of malignant transformation and poor prognosis of OSCC.
Sesame oil pulling can be a novel, cost-effective therapeutic agent with no side effects for clinical and psychological improvement of this chronic debilitating disorder. However, longitudinal studies in larger population is proposed for validation.