局部治疗后，用消融分数激光和vismodegib进行鼠皮肤中早期基底细胞癌的转录组分析
Transcriptomic Analysis of Early-Stage Basal Cell Carcinomas in Murine Skin Following Topical Treatments With Ablative Fractional Laser and Vismodegib
影响因子:3.10000
分区:医学3区 / 皮肤病学2区
发表日期:2024 Oct
作者:
Kristian Kåber Pedersen, Merete Hædersdal, Uffe Høgh Olesen, Thomas Litman
摘要
最近的研究表明，烧烤分数激光器（AFL）可以抑制刺猬途径，增强免疫浸润和清晰的基底细胞癌（BCC）。在这项研究中，我们应用了RNA测序，以进一步表征AFL对含有早期显微镜BCC鼠皮肤的转录组的影响，与刺猬抑制剂Vismodegib的局部应用相反。我们的结果表明，鼠皮肤中的BCC诱导主要与基因上调有关（显着上调的基因：277，显着下调基因：24）。通过Ingenuity途径分析对这些基因的表征表明，肿瘤诱导与BCC和Sonic刺猬信号的激活有关。 AFL和Vismodegib治疗都扭转了这些变化，Vismodegib通过逆转大多数上调的基因（AFL：59/277; Vismodegib：180/277）表现出了出色的性能。出乎意料的是，Ingenity途径分析还表明，AFL和Vismodegib治疗都引起了相当大的免疫细胞浸润。基于基因集富集分析和细胞类型反卷积，AFL治疗导致最大的免疫细胞募集，这两种治疗方法主要由浸润性嗜中性粒细胞，巨噬细胞和单核细胞组成。总之，在AFL和Vismodegib处理后，在BCC皮肤中观察到的独特作用表明两种干预措施之间的关键差异。 AFL或Vismodegib治疗的未来应用可能会利用其个人影响，例如，通过将AFL对免疫系统的影响与其他局部治疗相结合。
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.