A comparative study of genital lichen sclerosus transcriptomes

Abstract

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 thought 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) with the objective to identify commonly deregulated genes. We observed a substantial heterogeneity of 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 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, changes in the expression levels of genes associated with autoimmune diseases and genes upregulated in squamous cell carcinoma were observed, including TNF, CCNB1 and RUNX3. There was no enrichment in HCV-derived polyU/UC insertions that were reported previously. Instead, we have identified a long non-coding RNA DRAIC with a large coding potential that is commonly upregulated in mGLS and VLS. Together, our results represent a comprehensive catalog of shared transcriptomic signatures including novel biomarkers and potential therapeutic targets.