Dysregulated Genes of the Epithelial Cell Development Pathway as Potential Mediators in the Pathogenesis of Oral Leukoplakia and Their Association With Head and Neck Squamous Cell Carcinoma

Background: Oral potentially malignant disorders (OPMDs) pose a significant risk for the development of oral cancer, particularly oral squamous cell carcinoma (OSCC), due to their tendency to exhibit dysplastic changes in the oral epithelium that can progress to malignancy. This study delved into the intricate gene expression profiles of oral leukoplakia tissues, explicitly focusing on unraveling potential biomarkers contributing to the advancement of OPMDs and OSCC. Methods: The study successfully identified the top 20 differentially expressed genes (DEGs) by leveraging advanced techniques, such as RNA sequencing and bioinformatics analysis. The DEGs were further investigated by employing the TCGA dataset (HNSCC, Firehose Legacy). Multiple tools, such as STRING, Metascape, and Panther, were used for gene enrichment and ontology analysis. Results: SLC7A11, CDSN, KRT24, and MSN were the notable genes that presented with the same expression profile among the two groups. Gene ontology and enrichment analysis revealed their crucial role in regulating oxidative stress, keratinocyte differentiation, and the motility of cancer cells. Among the four genes, SLC7A11, CDSN, and MSN were upregulated, and the fourth one, KRT24 was downregulated in both datasets. The upregulation of KRT24 and CDSN was found to correlate with good prognosis, while SLC7A11 and MSN were found to exhibit poor prognosis. Conclusion: The study findings shed light on the possibility of these genes serving as early detection biomarkers and offering promising targets for therapeutic interventions. Additionally, the research emphasizes the need to explore further the genetic, epigenetic, and environmental factors influencing these expression patterns and validate these findings in clinical settings.