Transcriptome Analysis Reveals Distinct Molecular Signatures Between Erosive and Non-Erosive Oral Lichen Planus

To identify molecular mechanisms distinguishing the erosive subtype of oral lichen planus (EOLP) from the non-erosive subtype (NEOLP) through transcriptomic analysis.

We analysed bulk RNA-seq data from 30 buccal mucosa samples (13 EOLP, 17 NEOLP) using differential expression, Gene Set Enrichment Analysis (GSEA), transcription factor inference, bulk transcriptome deconvolution with xCell 2.0, metabolic flux simulation and novel pathway correlation analysis combining Gene Set Variation Analysis (GSVA) with Differential Gene Correlation Analysis (DGCA).

Three molecular signatures distinguished EOLP from NEOLP. First, metabolic-inflammatory coordination was disrupted in EOLP, with reversed correlations between integrated stress response regulators and metabolic pathways. Second, EOLP showed concurrent suppression of cell cycle and senescence programs, suggesting an altered epithelial state. Third, inflammatory profiling revealed myeloid-skewed activation (elevated SPI1/PU.1), enrichment of bacterial-response pathways, and loss of epithelial barrier signatures (GRHL2, keratinization). Mitochondrial dysfunction with selective Complex IV upregulation further supported a myeloid-driven metabolic remodelling in EOLP.

EOLP is characterised by disrupted metabolic-stress coordination, epithelial dysregulation, and myeloid-dominant inflammation. Our findings support a model in which microbial-associated stimuli may drive myeloid-centred metabolic reprogramming that sustains chronic inflammatory activity in EOLP. These results highlight potential therapeutic axes including restoration of metabolic-inflammatory balance, modulation of microbial influences, and epithelial barrier repair, although validation in larger cohorts and higher-resolution studies is required.