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

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dc.contributor.author Segura Tigell, Sonia
dc.contributor.author Gadea, Alejandra
dc.contributor.author Nonell Mazelón, Lara
dc.contributor.author Andrades, Evelyn
dc.contributor.author Sánchez, Silvia
dc.contributor.author Pujol Vallverdú, Ramon Maria
dc.contributor.author Hernández Muñoz, María Inmaculada
dc.contributor.author Toll Abelló, Agustín
dc.date.accessioned 2020-10-28T07:44:38Z
dc.date.available 2020-10-28T07:44:38Z
dc.date.issued 2020
dc.identifier.citation Segura S, Gadea A, Nonell L, Andrades E, Sánchez S, Pujol R. et al. Identification of differentially expressed genes in actinic keratosis samples treated with ingenol mebutate gel. PLoS One. 2020 May 15; 15(5):e0232146. DOI: 10.1371/journal.pone.0232146
dc.identifier.issn 1932-6203
dc.identifier.uri http://hdl.handle.net/10230/45597
dc.description.abstract 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.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Public Library of Science (PLoS)
dc.rights Copyright © 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.
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.subject.other Queratosi actínica -- Tractament
dc.title Identification of differentially expressed genes in actinic keratosis samples treated with ingenol mebutate gel
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1371/journal.pone.0232146
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


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