Differential normal skin transcriptomic response in total body irradiated mice exposed to scattered versus scanned proton beams

Abstract

Proton therapy allows to avoid excess radiation dose on normal tissues. However, there are some limitations. Indeed, passive delivery of proton beams results in an increase in the lateral dose upstream of the tumor and active scanning leads to strong differences in dose delivery. This study aims to assess possible differences in the transcriptomic response of skin in C57BL/6 mice after TBI irradiation by active or passive proton beams at the dose of 6 Gy compared to unirradiated mice. In that purpose, total RNA was extracted from skin samples 3 months after irradiation and RNA-Seq was performed. Results showed that active and passive delivery lead to completely different transcription profiles. Indeed, 140 and 167 genes were differentially expressed after active and passive scanning compared to unirradiated, respectively, with only one common gene corresponding to RIKEN cDNA 9930021J03. Moreover, protein–protein interactions performed by STRING analysis showed that 31 and 25 genes are functionally related after active and passive delivery, respectively, with no common gene between both types of proton delivery. Analysis showed that active scanning led to the regulation of genes involved in skin development which was not the case with passive delivery. Moreover, 14 ncRNA were differentially regulated after active scanning against none for passive delivery. Active scanning led to 49 potential mRNA-ncRNA pairs with one ncRNA mainly involved, Gm44383 which is a miRNA. The 43 genes potentially regulated by the miRNA Gm44393 confirmed an important role of active scanning on skin keratin pathway. Our results demonstrated that there are differences in skin gene expression still 3 months after proton irradiation versus unirradiated mouse skin. And strong differences do exist in late skin gene expression between scattered or scanned proton beams. Further investigations are strongly needed to understand this discrepancy and to improve treatments by proton therapy.

Radiation Type- and Dose-Specific Transcriptional Responses across Healthy and Diseased Mammalian Tissues

“…For database construction, we performed text mining in PubMed, using appropriate keywords across studies that experimentally address the overall effect of five high- and low-LET radiation types of interest in a broad range of mammalian cell types, including human, mouse and rat study model systems. The database includes 7436 entries, with a total of 3730 unique genes derived from 14 tissues/cell lines [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 ]. For each entry, the following information was provided: Differential expression of genes: The expression status of the corresponding genes (i.e., up or downregulated in irradiated compared to non-irradiated tissue/cell control groups).…”

Can We Compare the Health-Related Quality of Life of Childhood Cancer Survivors Following Photon and Proton Radiation Therapy? A Systematic Review

“…Studies were included if they were peer-reviewed, original research articles published in the English language, if a validated patient-reported outcomes tool was used to measure quality of life, and if participants were children diagnosed with cancer between ages 0 to 21 years [ 17 ]. Studies were eligible if participants received external beam RT (XRT or PRT), with total body irradiation excluded, as a comparable technique using particle therapy is not in clinical use [ 18 ]. If an analysis of a patient cohort included patients with and without RT treatment, 50% or more participants were required to have received RT.…”

Making connections: the scientific impact and mentoring legacy of Dr. John E. Moulder

“…During the U19 award period, seven trainees benefited from resources provided by the program and were able to parlay their experiences into presentations at meetings of the RRS, the International Congress of Radiation Research, and the American Society for Therapeutic Radiation Oncology. Most of those fellows that were supported by the MCW Core continue to publish papers in the radiation field ( Prevost et al 2018 ; Lenarczyk et al 2019 ; Wunderle et al 2019 ; Lenarczyk et al 2020 ; Leduc et al 2021 ; Raber et al 2021 ; Hsu et al 2022 ; Liu et al 2022 ) and obtain follow-on funding (e.g. pilots or full research grants).…”