Transcriptomic analysis of early-stage basal cell carcinomas in murine skin following ablative fractional laser and vismodegib treatment
Recent studies have demonstrated that ablative fractional laser (AFL) can inhibit the hedgehog pathway, enhance immune infiltration, and clear basal cell carcinomas (BCCs) in murine models. In this study, we applied RNA sequencing to further characterize the impact of AFL on the transcriptome of murine skin containing early-stage microscopic BCCs, contrasting it with the effects of the FDA approved hedgehog inhibitor vismodegib. Our results showed that BCC induction in murine skin was primarily linked to gene upregulation. Both AFL and vismodegib treatments were able to reverse this upregulation with vismodegib demonstrating superior performance by reversing the most genes (AFL: 59/277; vismodegib 180/277). Surprisingly, Ingenuity Pathway Analysis revealed that both treatments also caused considerable immune cell infiltration. Based on gene set enrichment analysis and cell type deconvolution, AFL treatment resulted in the largest immune cell recruitment, which for both treatments primarily consisted of infiltrating neutrophils, macrophages, and monocytes. In conclusion, the distinct effects observed in BCC skin following AFL and vismodegib treatment highlight key differences between the two interventions. Future applications of AFL or vismodegib treatments could leverage their individual effects, for example by combining AFL's effects on the immune system with other topical treatments. Overall design: Our goal was to investigate the effects of ablative fractional laser and topical vismodegib treatment on a mouse that develops basal cell carcinomas following induction with tamoxifen and x-ray treatment (Ptch1+/- K14-CreER2 p53fl/fl). We treated 1cm2 skin pieces containing early-stage BCCs with AFL and vismodegib. As controls, we included healthy skin (non-induced) and BCC skin (induced skin).