Identification of GALNT18, HOMER3, and NRP2 as shared molecular signatures associated with stromal remodeling and immune suppression in oral mucosal malignancy-associated disorders

Background. Oral submucous fibrosis (OSF), oral leukoplakia (OLK), and oral squamous cell carcinoma (OSCC) are prevalent disorders associated with oral mucosal malignancy. However, the common mechanisms underlying the progression and shared characteristics of these malignancy-associated disorders remain unclear. This study aims to investigate the core common differentially expressed genes (DEGs) shared by OSF, OLK, and OSCC, providing novel targets for the diagnosis and evaluation of oral mucosal malignancy-associated disorders. Methods. We mined the Gene Expression Omnibus (GEO) database to pinpoint overlapping transcriptomic signatures across OSF, OLK, and OSCC. Functional enrichment analyses, utilizing Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), were performed to map biological pathways. Protein–protein interaction (PPI) networks were constructed to identify candidate genes. These candidates were further screened via Least Absolute Shrinkage and Selection Operator (LASSO) regression and Receiver Operating Characteristic (ROC) validation to prioritize core markers. Additionally, immune infiltration assessments and single-gene Gene Set Enrichment Analysis (GSEA) were conducted to explore mechanistic links, while survival analysis was employed to evaluate prognostic value. Results. We identified 94 co-expressed genes, which were primarily clustered in biological processes related to extracellular matrix (ECM) remodeling, epithelial–mesenchymal transition (EMT), and immune regulation. Through rigorous screening, GALNT18 , HOMER3 , and NRP2 were prioritized as the final core genes. These markers demonstrated consistent correlations with specific infiltrating immune cells and ECM-related signaling pathways. Notably, while all three genes served as robust diagnostic markers, high NRP2 expression was specifically associated with poor overall survival.