Xu Mengmeng, Peng Qiliang, Zhang Jun, Xu Zhiming, Cheng Xinyang, Cao Zhifei, Zhang Yongsheng
Department of Pathology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
Dose Response. 2025 May 20;23(2):15593258251342837. doi: 10.1177/15593258251342837. eCollection 2025 Apr-Jun.
FLASH radiotherapy is garnering attention for its capacity to diminish skin toxicity without compromising tumoricidal efficacy, presenting a stark contrast to conventional (CONV) radiotherapy. Despite its promise, the underlying molecular mechanisms of FLASH irradiation (FLASH-IR) on skin are not yet fully elucidated.
This study investigated the transcriptomic responses of human foreskin fibroblast cells (HFF-1) via the FLASH-IR or CONV irradiation (CONV-IR), employing the next-generation RNA sequencing (RNA-seq) to capture the gene expression profiles. Our comparative analysis aimed to dissect the cellular and molecular pathways influenced by these two irradiation methods.
We identified a spectrum of differentially expressed genes (DEGs), signaling pathways, and transcriptional networks that were either shared or divergent between FLASH-IR and CONV-IR. Particularly, transcription factor NR4A1 showed significant upregulation in response to FLASH-IR, while chromatin stability factor ELF3 was markedly downregulated following CONV-IR. The top 10 up-regulated DEGs were subjected to qPCR validation, confirming their differential expression in response to FLASH-IR and CONV-IR.
Collectively, our findings delineate unique regulatory landscapes of FLASH-IR and CONV-IR on skin cells, corroborating established effects and shedding new light on the molecular interplay within the context of ultra-high dose radiation.
FLASH放疗因其在不影响肿瘤杀伤效果的情况下降低皮肤毒性的能力而备受关注，这与传统（CONV）放疗形成鲜明对比。尽管前景广阔，但FLASH照射（FLASH-IR）对皮肤的潜在分子机制尚未完全阐明。
本研究通过FLASH-IR或CONV照射（CONV-IR）研究人包皮成纤维细胞（HFF-1）的转录组反应，采用下一代RNA测序（RNA-seq）来捕获基因表达谱。我们的比较分析旨在剖析受这两种照射方法影响的细胞和分子途径。
我们鉴定了一系列在FLASH-IR和CONV-IR之间共享或不同的差异表达基因（DEG）、信号通路和转录网络。特别是，转录因子NR4A1在FLASH-IR刺激下显著上调，而染色质稳定性因子ELF3在CONV-IR后明显下调。对前10个上调的DEG进行qPCR验证，证实了它们在FLASH-IR和CONV-IR刺激下的差异表达。
总体而言，我们的研究结果描绘了FLASH-IR和CONV-IR对皮肤细胞独特的调控格局，证实了已有的效应，并为超高剂量辐射背景下的分子相互作用提供了新的见解。
