A Shared Epithelial Barrier Program Across Mucocutaneous Lichen Planus: A Compartment-Aware Multi-Cohort Transcriptomic Reanalysis

Oral lichen planus (LP) is widely described as molecularly distinct from cutaneous LP, yet most supporting transcriptomic evidence compares mucosal epithelium with full-thickness skin. We reanalysed four public microarray series covering oral, genital and cutaneous LP (101 arrays) with matched microRNA arrays, using covariate-adjusted models, meta-analysis, cross-platform integration, a within-platform site-by-disease interaction model, pathway and deconvolution scoring and a test of experimentally supported microRNA–target interactions. Eighty-five genes were differentially expressed at both discovery sites, 83 concordantly, dominated by cornified-envelope and keratinisation genes; BPIFC, CDSN and WFDC12 replicated in all four cohorts. A 52-gene barrier score separated lesional from control tissue in the discovery and genital cohorts (AUC 0.98–1.00, partly in-sample), and panels derived at one LP site transferred across study, platform and site (AUC 0.95–0.99), but the score did not reach significance in the only fully independent oral cohort (AUC 0.76, p = 0.13). In comparator series, the programme was also induced in psoriasis and partly in cutaneous lupus, but not in atopic dermatitis, eosinophilic oesophagitis or periodontitis, so it is shared rather than LP-specific. Interferon and MYC-target activity and several immune populations were higher in cutaneous LP, but an epithelial:immune compartment proxy showed that cutaneous biopsies were full-thickness whereas mucosal biopsies were epithelium-only, confounding this contrast. Within one platform, 292 genes showed an oral-versus-genital interaction. Neither miR-20a-5p nor miR-34a-5p tracked barrier expression, and across 222,203 supported microRNA–target pair correlations were predominantly positive rather than inverse. Across LP sites, a reproducible epithelial barrier programme is the most consistent shared feature, although it is not specific to LP and its transfer to independent cohorts remains provisional; reported immune divergence cannot be separated from the biopsy compartment.