Proteomic Profiling of Serum-Derived Exosomes in Oral Lichen Planus: FN1-C3-ECM Crosstalk as a Potential Novel Therapeutic Target.

Abstract

Objective: Oral lichen planus (OLP) is a chronic inflammatory disorder with malignant potential. The aim is to characterize serum exosome protein expression profiles in patients diagnosed with OLP and to identify potential disease-associated candidate proteins.

Methods: Serum samples were collected from 30 participants, comprising erosive OLP patients, non-erosive OLP patients, and healthy controls (n = 10 per group). Serum exosome proteomes were compared across groups following validation of exosomal integrity using nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and Western blotting. Label-free quantitative proteomic profiling was performed with Orbitrap Exploris 480 mass spectrometry, integrated with bioinformatics analyses to identify differentially expressed proteins.

Results: About 138 differentially expressed proteins (DEPs, 39↑/99↓) in OLP patients vs controls, with subtype-specific profiles (70 DEPs in non-erosive, 99 in erosive). Gene Ontology (GO) enrichment analysis indicated that these proteins were predominantly associated with extracellular vesicles, protein binding, and immune response regulation. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis highlighted enrichment in the complement and coagulation cascade (p < 0.05), platelet activation, and focal adhesion pathways. Protein-protein interaction (PPI) network analysis identified central proteins including fibronectin 1 (FN1), complement component 3 (C3), integrin subunit beta 3 (ITGB3), vinculin (VCL), and SRC proto-oncogene (SRC). Among these, FN1 and C3 were implicated in mediating epithelial-extracellular matrix (ECM) separation and thromboinflammatory activity.

Conclusion: The identified differentially expressed proteins in serum exosomes and their association with the complement and coagulation cascade pathway appear to contribute to the pathogenesis and progression of OLP. FN1 and C3 dysregulation directly contributes to OLP pathogenesis via immune-stromal crosstalk. Core proteins such as FN1 and C3 may serve as promising non-invasive diagnostic biomarkers and therapeutic targets, warranting further validation.