Establishment of diagnostic markers for differentiation of oral lichen planus and oral erythroleukoplakia with lichenoid features through a transcriptomic profile analysis.

BACKGROUND/PURPOSE: Oral lichen planus (OLP) frequently overlaps clinically and histopathologically with oral erythroleukoplakia (OEL), a high-risk oral potentially malignant disorder. OEL with lichenoid features (OEL-L) may closely mimic OLP, resulting in diagnostic uncertainty and inappropriate management. This study aimed to characterize immune and epithelial transcriptomic differences between OLP and OEL-L and to identify potential diagnostic biomarkers. MATERIALS AND METHODS: Formalin-fixed paraffin-embedded specimens from 6 OLP and 6 OEL-L cases were analyzed retrospectively. Diagnoses were established according to World Health Organization criteria. Immune and epithelial gene expression profiles were assessed using the NanoString nCounter Autoimmune Discovery and PanCancer Progression panels. Differentially expressed genes were identified using a fold change >5 and P < 0.01. RESULTS: OLP lesions showed marked activation of T-cell-associated immune pathways, including T-cell receptor signaling, natural killer cell cytotoxicity, and type I interferon responses. In contrast, OEL-L exhibited global suppression of adaptive immune signatures with enrichment of metabolic and oxidative stress pathways. OEL-L demonstrated increased expression of B-cell- and plasma cell-related genes [tumor necrotic factor receptor superfamily member 17 (TNFRSF17), CD79A] and epithelial-derived C-X-C motif ligand 8 (CXCL8) and matrix metalloproteinase 12 (MMP12), accompanied by stromal and extracellular matrix-remodeling signatures. CONCLUSION: Distinct immune and epithelial transcriptomic profiles differentiate OLP from OEL-L. CXCL8, MMP12, and B-cell-associated markers may serve as useful adjunctive biomarkers for pathological discrimination.