Identification of differentially expressed genes in actinic keratosis samples treated with ingenol mebutate gel

Actinic keratosis is a common skin disease that may progress to invasive squamous cell carcinoma if left untreated. Ingenol mebutate has demonstrated efficacy in field treatment of actinic keratosis. However, molecular mechanisms on ingenol mebutate response are not yet fully understood. In this stu...

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Autores: Segura Tigell, Sonia, Gadea, Alejandra, Nonell Mazelon, Lara, 1972-, Andrades, Evelyn, Sánchez, Silvia, Pujol Vallverdú, Ramon Maria, Hernández Muñoz, María Inmaculada, Toll Abelló, Agustín
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/45597
Acceso en línea:http://hdl.handle.net/10230/45597
http://dx.doi.org/10.1371/journal.pone.0232146
Access Level:acceso abierto
Palabra clave:Queratosi actínica -- Tractament
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spelling Identification of differentially expressed genes in actinic keratosis samples treated with ingenol mebutate gelSegura Tigell, SoniaGadea, AlejandraNonell Mazelon, Lara, 1972-Andrades, EvelynSánchez, SilviaPujol Vallverdú, Ramon MariaHernández Muñoz, María InmaculadaToll Abelló, AgustínQueratosi actínica -- TractamentActinic keratosis is a common skin disease that may progress to invasive squamous cell carcinoma if left untreated. Ingenol mebutate has demonstrated efficacy in field treatment of actinic keratosis. However, molecular mechanisms on ingenol mebutate response are not yet fully understood. In this study, we evaluated the gene expression profiles of actinic keratosis lesions before and after treatment with ingenol mebutate using microarray technology. Actinic keratoses on face/scalp of 15 immunocompetent patients were identified and evaluated after treatment with topical ingenol mebutate gel 0.015%, applied once daily for 3 consecutive days. Diagnostic and clearance of lesions was determined by clinical, dermoscopic, and reflectance confocal microscopy criteria. Lesional and non-lesional skin biopsies were subjected to gene expression analysis profiled by Affymetrix microarray. Differentially expressed genes were identified, and enrichment analyses were performed using STRING database. At 8 weeks post-treatment, 60% of patients responded to ingenol mebutate therapy, achieving complete clearance in 40% of cases. A total of 128 differentially expressed genes were identified following treatment, and downregulated genes (114 of 128) revealed changes in pathways important to epidermal development, keratinocyte differentiation and cornification. In responder patients, 388 downregulated genes (of 450 differentially expressed genes) were also involved in development/differentiation of the epidermis, and immune system-related pathways, such as cytokine and interleukin signaling. Cluster analysis revealed two relevant clusters showing upregulated profile patterns in pre-treatment actinic keratoses of responders, as compared to non-responders. Again, differentially expressed genes were mainly associated with cornification, keratinization and keratinocyte differentiation. Overall, the present study provides insight into the gene expression profile of actinic keratoses after treatment with ingenol mebutate, as well as identification of genetic signatures that could predict treatment response.Public Library of Science (PLoS)202020202020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/45597http://dx.doi.org/10.1371/journal.pone.0232146reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésCopyright © 2020 Segura et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, https://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10230/455972026-05-29T05:05:01Z
dc.title.none.fl_str_mv Identification of differentially expressed genes in actinic keratosis samples treated with ingenol mebutate gel
title Identification of differentially expressed genes in actinic keratosis samples treated with ingenol mebutate gel
spellingShingle Identification of differentially expressed genes in actinic keratosis samples treated with ingenol mebutate gel
Segura Tigell, Sonia
Queratosi actínica -- Tractament
title_short Identification of differentially expressed genes in actinic keratosis samples treated with ingenol mebutate gel
title_full Identification of differentially expressed genes in actinic keratosis samples treated with ingenol mebutate gel
title_fullStr Identification of differentially expressed genes in actinic keratosis samples treated with ingenol mebutate gel
title_full_unstemmed Identification of differentially expressed genes in actinic keratosis samples treated with ingenol mebutate gel
title_sort Identification of differentially expressed genes in actinic keratosis samples treated with ingenol mebutate gel
dc.creator.none.fl_str_mv Segura Tigell, Sonia
Gadea, Alejandra
Nonell Mazelon, Lara, 1972-
Andrades, Evelyn
Sánchez, Silvia
Pujol Vallverdú, Ramon Maria
Hernández Muñoz, María Inmaculada
Toll Abelló, Agustín
author Segura Tigell, Sonia
author_facet Segura Tigell, Sonia
Gadea, Alejandra
Nonell Mazelon, Lara, 1972-
Andrades, Evelyn
Sánchez, Silvia
Pujol Vallverdú, Ramon Maria
Hernández Muñoz, María Inmaculada
Toll Abelló, Agustín
author_role author
author2 Gadea, Alejandra
Nonell Mazelon, Lara, 1972-
Andrades, Evelyn
Sánchez, Silvia
Pujol Vallverdú, Ramon Maria
Hernández Muñoz, María Inmaculada
Toll Abelló, Agustín
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Queratosi actínica -- Tractament
topic Queratosi actínica -- Tractament
description Actinic keratosis is a common skin disease that may progress to invasive squamous cell carcinoma if left untreated. Ingenol mebutate has demonstrated efficacy in field treatment of actinic keratosis. However, molecular mechanisms on ingenol mebutate response are not yet fully understood. In this study, we evaluated the gene expression profiles of actinic keratosis lesions before and after treatment with ingenol mebutate using microarray technology. Actinic keratoses on face/scalp of 15 immunocompetent patients were identified and evaluated after treatment with topical ingenol mebutate gel 0.015%, applied once daily for 3 consecutive days. Diagnostic and clearance of lesions was determined by clinical, dermoscopic, and reflectance confocal microscopy criteria. Lesional and non-lesional skin biopsies were subjected to gene expression analysis profiled by Affymetrix microarray. Differentially expressed genes were identified, and enrichment analyses were performed using STRING database. At 8 weeks post-treatment, 60% of patients responded to ingenol mebutate therapy, achieving complete clearance in 40% of cases. A total of 128 differentially expressed genes were identified following treatment, and downregulated genes (114 of 128) revealed changes in pathways important to epidermal development, keratinocyte differentiation and cornification. In responder patients, 388 downregulated genes (of 450 differentially expressed genes) were also involved in development/differentiation of the epidermis, and immune system-related pathways, such as cytokine and interleukin signaling. Cluster analysis revealed two relevant clusters showing upregulated profile patterns in pre-treatment actinic keratoses of responders, as compared to non-responders. Again, differentially expressed genes were mainly associated with cornification, keratinization and keratinocyte differentiation. Overall, the present study provides insight into the gene expression profile of actinic keratoses after treatment with ingenol mebutate, as well as identification of genetic signatures that could predict treatment response.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/45597
http://dx.doi.org/10.1371/journal.pone.0232146
url http://hdl.handle.net/10230/45597
http://dx.doi.org/10.1371/journal.pone.0232146
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Public Library of Science (PLoS)
publisher.none.fl_str_mv Public Library of Science (PLoS)
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
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