Transcriptional signature for dysplastic epidermal development in human pre-malignant skin

ABSTRACT: Actinic keratosis (AK) is a prolific precancerous skin lesion, which occurs in susceptible individuals due to chronic ultraviolet radiation exposure, with a propensity to develop into malignant squamous cell carcinoma (SCC). The histopathologic features of AKs include a dysplastic epithelium that is frequently, but not always, spatially limited to the interfollicular epithelium. However, the upper follicular epithelium, although equally susceptible to ultraviolet radiation (UVR) exposure, is commonly spared of dysplasia. To address these issues, our approach sought to leverage this phenomenon by profiling UVR-susceptible (interfollicular) versus -refractory (follicular) epithelium using spatial transcriptomic analysis of AK tissue sections. Unsupervised clustering analysis segregated transcriptionally distinct regions of epithelium in AK lesions that spatially overlapped with either normal follicular or dysplastic interfollicular regions and identified a total of 193 dysregulated genes in dysplastic interfollicular epidermal clusters that were conserved across multiple AKs. Next, CellChat analysis identified highly enriched cell-cell communication pathways primarily between dermal and dysplastic epidermal clusters, suggesting that perturbations in dermal-epidermal communication may be early drivers of epidermal dysplasia. Collectively, our findings elaborate a first-of-its-kind transcriptional signature for early dysplastic epidermal development in human pre-malignant skin and provide much needed insight into the longstanding clinical observation of susceptible (interfollicular) versus refractory (follicular) epithelium to ultraviolet radiation-induced dysplasia.

ORGANISM(S): human skin metagenome

PROVIDER: GSE294844 | GEO | 2025/04/19

REPOSITORIES: GEO