A Comparative Study of Genital Lichen Sclerosus Transcriptomes

Genital lichen sclerosus (GLS) is a chronic inflammatory dermatosis that affects the genital skin. Despite different clinical manifestations, the pathogenesis of GLS in men and women is believed to be common and is attributed to a combination of autoimmune and genetic factors. In this study, we compared the transcriptomic profiles of penile (mGLS) and vulvar lichen sclerosus (VLS), aiming to identify commonly deregulated genes. We observed a substantial heterogeneity in the transcriptomic signatures in mGLS samples, which is driven by different compositions of immune infiltrates. In mGLS, gene expression signatures strongly indicate epidermis dysfunction and overexpression of the epithelial inflammation marker Keratin 6 (KRT6) and chitinase CHIT1. No significant changes in the expression levels of known GLS markers, such as VIM, CTNNB1, LGALS7 and ECM1, were detected. However, significant changes in the expression levels of the genes associated with autoimmune diseases and the genes upregulated in squamous cell carcinoma, including TNF, CCNB1 and RUNX3, were observed. There was no enrichment in the polyU/UC insertions that were reported previously. Instead, we have identified a long non-coding RNA DRAIC with a high coding potential that is commonly upregulated in mGLS and VLS. Taken together, our results provide a comprehensive picture of the shared transcriptomic signatures, including novel biomarkers and potential therapeutic targets.