Transcriptomic Analysis of Early-Stage Basal Cell Carcinomas in Murine Skin Following Topical Treatments With Ablative Fractional Laser and Vismodegib

IF 3.5 3区 医学 Q1 DERMATOLOGY
Kristian Kåber Pedersen, Merete Hædersdal, Uffe Høgh Olesen, Thomas Litman
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Abstract

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 characterise the impact of AFL on the transcriptome of murine skin containing early-stage microscopic BCCs, contrasting it with the effects of topical application of the hedgehog inhibitor vismodegib. Our results showed that BCC induction in murine skin was primarily linked to gene upregulation (significantly upregulated genes: 277, significantly downregulated genes: 24). Characterisation of these genes with Ingenuity Pathway Analysis showed that tumour induction was associated with activation of BCC and Sonic Hedgehog signalling. Both AFL and vismodegib treatments reversed these changes, with vismodegib demonstrating superior performance by reversing most of the upregulated genes (AFL: 59/277; vismodegib: 180/277). Surprisingly, Ingenuity Pathway Analysis also revealed that both AFL and vismodegib treatments 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 suggest key differences between the two interventions. Future applications of AFL or vismodegib treatments could leverage their individual effects, for example by combining the effect of AFL on the immune system with other topical treatments.

Abstract Image

用烧蚀点阵激光和 Vismodegib 局部治疗后早期小鼠皮肤基底细胞癌的转录组分析
最近的研究表明,消融点阵激光(AFL)可以抑制刺猬通路、增强免疫浸润并清除小鼠模型中的基底细胞癌(BCC)。在本研究中,我们应用 RNA 测序进一步描述了 AFL 对含有早期微小 BCC 的小鼠皮肤转录组的影响,并将其与局部应用刺猬抑制剂 vismodegib 的效果进行了对比。我们的研究结果表明,小鼠皮肤的BCC诱导主要与基因上调有关(显著上调的基因:277个,显著下调的基因:24个)。利用 Ingenuity Pathway Analysis 对这些基因进行的分析表明,肿瘤诱导与 BCC 和 Sonic Hedgehog 信号的激活有关。AFL和vismodegib治疗都能逆转这些变化,其中vismodegib通过逆转大多数上调基因表现出更优越的性能(AFL:59/277;vismodegib:180/277)。令人惊讶的是,Ingenuity Pathway 分析还显示,AFL 和 vismodegib 治疗都会导致大量免疫细胞浸润。根据基因组富集分析和细胞类型解旋,AFL 处理导致了最大的免疫细胞招募,两种处理都主要包括浸润的中性粒细胞、巨噬细胞和单核细胞。总之,AFL 和 vismodegib 治疗后在 BCC 皮肤上观察到的不同效果表明了这两种干预措施之间的关键差异。AFL或vismodegib疗法的未来应用可以充分利用它们各自的效果,例如将AFL对免疫系统的影响与其他局部治疗结合起来。
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来源期刊
Experimental Dermatology
Experimental Dermatology 医学-皮肤病学
CiteScore
6.70
自引率
5.60%
发文量
201
审稿时长
2 months
期刊介绍: Experimental Dermatology provides a vehicle for the rapid publication of innovative and definitive reports, letters to the editor and review articles covering all aspects of experimental dermatology. Preference is given to papers of immediate importance to other investigators, either by virtue of their new methodology, experimental data or new ideas. The essential criteria for publication are clarity, experimental soundness and novelty. Letters to the editor related to published reports may also be accepted, provided that they are short and scientifically relevant to the reports mentioned, in order to provide a continuing forum for discussion. Review articles represent a state-of-the-art overview and are invited by the editors.
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