The Screening, Identifiction And Clinical Application Of Five Novel Target Biomarkers In Oral Submucous Fibrosis

Background:Oral submucous fibrosis(OSF) is a high-risk precancerous condition of the oral cavity.Areca-nut chewing is its key etiological factor,but the full pathogenesis is still obscure.Method:In this study,microarray analysis was used to characterize the mRNA changes of 14500 genes in 40SF and 4 normal buccal mucosa samples to identify novel biomarkers of OSF.Five candidate genes with the most differential changes were chosen for validation.The correlation between clinicopathologic parameters of 66 OSF patients and the expression of each gene was assessed by immunohistochemistry.Result:The microarray analysis showed that 661 genes were up-regulated(fold value>2) and 129 genes were down-regulated(fold value<0.5) in OSF(q<0.01).And top three up-regulated genes [Loricrin,Cartilage oligomeric matrix protein(COMP),Cys-X-Cys ligand 9(CXCL9)]with the largest fold changes and top two down-regulated genes[keratin 19(KRT19),cytochrome P450 3A5(CYP 3A5)]with the most significantly differential changes in OSF were chosen as candidate biomarkers.In immunohistochemical results,the expression of Loricrin and COMP showed statistically significant association with histological grade of OSF(P=0.03 and 0.006, respectively).COMP was found to be overexpressed frequently in the patients with the habit of areca-nut chewing more than 4 years(P= 0.002).CYP 3A5 was revealed an inverse correlation with histological grade(P=0.04).Conclusion:This pilot study demonstrated 5 novel genes might play important roles in the pathogenesis of OSF and be clinically useful for early detection of OSF.