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...

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Autores principales:	Alexandre Leduc, Samia Chaouni, Frédéric Pouzoulet, Ludovic De Marzi, Frédérique Megnin-Chanet, Erwan Corre, Dinu Stefan, Jean-Louis Habrand, François Sichel, Carine Laurent
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4a4f1e1463b84baf95bd357afe03d024
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spelling	oai:doaj.org-article:4a4f1e1463b84baf95bd357afe03d0242021-12-02T11:36:36ZDifferential normal skin transcriptomic response in total body irradiated mice exposed to scattered versus scanned proton beams10.1038/s41598-021-85394-02045-2322https://doaj.org/article/4a4f1e1463b84baf95bd357afe03d0242021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85394-0https://doaj.org/toc/2045-2322Abstract 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.Alexandre LeducSamia ChaouniFrédéric PouzouletLudovic De MarziFrédérique Megnin-ChanetErwan CorreDinu StefanJean-Louis HabrandFrançois SichelCarine LaurentNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Alexandre Leduc Samia Chaouni Frédéric Pouzoulet Ludovic De Marzi Frédérique Megnin-Chanet Erwan Corre Dinu Stefan Jean-Louis Habrand François Sichel Carine Laurent Differential normal skin transcriptomic response in total body irradiated mice exposed to scattered versus scanned proton beams
description	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.
format	article
author	Alexandre Leduc Samia Chaouni Frédéric Pouzoulet Ludovic De Marzi Frédérique Megnin-Chanet Erwan Corre Dinu Stefan Jean-Louis Habrand François Sichel Carine Laurent
author_facet	Alexandre Leduc Samia Chaouni Frédéric Pouzoulet Ludovic De Marzi Frédérique Megnin-Chanet Erwan Corre Dinu Stefan Jean-Louis Habrand François Sichel Carine Laurent
author_sort	Alexandre Leduc
title	Differential normal skin transcriptomic response in total body irradiated mice exposed to scattered versus scanned proton beams
title_short	Differential normal skin transcriptomic response in total body irradiated mice exposed to scattered versus scanned proton beams
title_full	Differential normal skin transcriptomic response in total body irradiated mice exposed to scattered versus scanned proton beams
title_fullStr	Differential normal skin transcriptomic response in total body irradiated mice exposed to scattered versus scanned proton beams
title_full_unstemmed	Differential normal skin transcriptomic response in total body irradiated mice exposed to scattered versus scanned proton beams
title_sort	differential normal skin transcriptomic response in total body irradiated mice exposed to scattered versus scanned proton beams
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/4a4f1e1463b84baf95bd357afe03d024
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Differential normal skin transcriptomic response in total body irradiated mice exposed to scattered versus scanned proton beams

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