Objective: The molecular mechanisms underlying the development of dysplasia in leukoplakia are unknown. We used RNA sequencing to examine the molecular and biological pathway differences in oral leukoplakia with and without oral epithelial dysplasia.
Materials and methods: Excisional biopsy specimens (25) were taken from 24 patients with oral leukoplakia diagnosed histopathologically as either oral epithelial dysplasia (13) or epithelial hyperplasia and keratosis without dysplasia (12). Transcriptome analysis used RNA sequencing, differential expression and hierarchical clustering. Biological signalling was examined by gene ontology, pathway and protein-protein interaction analysis.
Results: Differential expression analysis showed distinction between the two groups identifying 47 genes as altered in leukoplakia with dysplasia, including SAA1, SAA2, KRT31, KRT37, KRT76, ROBO2, DNAJB5 and DNAJA4. Using hierarchical clustering, dysplastic leukoplakia readily segregated from leukoplakia without dysplasia. Pathway and ontology enrichment analysis provided evidence that downregulation of extracellular matrix (ECM) pathways was a feature of dysplastic lesions.
Conclusion: Our results suggest that there are detectable changes in the molecular profile of oral leukoplakia exhibiting dysplasia including downregulated ECM as a distinguishing feature of dysplastic lesions. This suggests that reactive changes in stroma may be an early manifestation of dysplastic development. Our study also demonstrates the feasibility of detecting such molecular changes in oral leukoplakia, providing avenues for further investigation of molecular mechanisms of oral dysplasia.
Keywords: RNA sequencing; epithelial dysplasia; gene expression profiling; leukoplakia.
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