Oral epithelial dysplasia with lichenoid features shares proteomic overlap with oral epithelial dysplasia without lymphocytic immune response

Objective: This study investigates the proteomic profiles of oral epithelial dysplasia with lichenoid features (OEDwithLF) and evaluates its relevance as a histopathological feature for lichenoid mucositis (LM) through differential proteomic characterization. Study Design: SWATH-MS proteomic profiling was conducted on FFPE samples from 6 OEDwithLF, 5 OED cases without associated lymphocytic infiltration, and 5 LM cases. Protein expression levels were quantified and compared. In silico analysis examined the biological and molecular functions of dysregulated proteins. Results: A total of 460 proteins were identified. Unsupervised clustering revealed significant differences between LM and OEDwithLF, with fewer differences observed between OEDwithLF and OED. Bioinformatic analysis indicated dysregulated proteins are involved in nucleic acid binding, ribosome function, and developmental biology. Key potential biomarkers include KRT17, LYSC, CAL5, and CRNN. Conclusions: The proteomic profile of OEDwithLF is similar to OED without associated lymphocytic infiltration, but significantly different from LM. OED is relevant in lichenoid tissues, and its proteomic changes can be detected. Although OED may coexist with interface mucositis, it is not a defining feature of LM. This challenges the exclusion of epithelial dysplasia from lichenoid diagnoses. Based on this hypothesis-generating study, further investigation is warranted.