SOX11 and GLIS2: Novel Biomarkers for Understanding the Progression of Oral Leukoplakia.

BACKGROUND: Oral leukoplakia (LP) is a common precancerous lesion that can progress to oral squamous cell carcinoma (OSCC). Although various risk factors have been identified, the molecular mechanisms and biomarkers of LP remain insufficiently understood. METHODS: This study integrated single-cell RNA sequencing with bulk RNA sequencing data from leukoplakia tissues to investigate the transcriptional regulatory mechanisms within LPtissues. Our aim is to identify key molecular markers and their associated pathways. Furthermore, by analyzing survival data from OSCC in the The Cancer Genome Atlas(TCGA) database, we assessed the prognostic significance of these molecular markers in tumors. Finally, we validated the potential roles of relevant molecular markers in the progression of leukoplakia using patient LP tissue samples. RESULTS: The analysis revealed that single-cell RNA sequencing data indicated that fibroblasts in LP tissues possess a unique gene regulatory network, exhibiting significantly different transcriptional characteristics compared to normal tissues. We identified SOX11 and GLIS2 as LP-specific molecular markers, with their expression significantly elevated in LP tissues compared to normal tissues. Transcriptomic profiling of LP reveals that SOX11 and GLIS2 positively correlate with the activation of epithelial-mesenchymal transition (EMT) and angiogenesis. Additionally, analysis of OSCC samples demonstrated that high expression levels of SOX11 and GLIS2 were associated with poor prognosis. Immunohistochemical staining further showed a gradual increase in the expression of SOX11 and GLIS2 during the progression of leukoplakia, supporting their potential application as biomarkers. CONCLUSION: As key transcription factors in LP, SOX11 and GLIS2 may influence the occurrence and development of lesions by regulating EMT and angiogenesis biological processes. They have the potential to serve as biomarkers and therapeutic targets for LP and OSCC, providing new insights into understanding the mechanisms of LP and developing treatment strategies.