Transcriptomic analysis identifies differences in gene expression in actinic keratoses after treatment with imiquimod and between responders and non responders

Abstract The presence of actinic keratoses (AKs) increases a patient’s risk of developing squamous cell carcinoma by greater than six-fold. We evaluated the effect of topical treatment with imiquimod on the tumor microenvironment by measuring transcriptomic differences in AKs before and after treatm...

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Autores principales:	Megan H. Trager, Emanuelle Rizk, Sharon Rose, Kuixi Zhu, Branden Lau, Benjamin T. Fullerton, Jaya Pradhan, Michael Moore, Ayush C. Srivastava, Giselle Singer, Robyn Gartrell, Rui Chang, Larisa J. Geskin, Yvonne M. Saenger, Gary Goldenberg
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6bb5791204724714b50998aaf52add66
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spelling	oai:doaj.org-article:6bb5791204724714b50998aaf52add662021-12-02T15:26:58ZTranscriptomic analysis identifies differences in gene expression in actinic keratoses after treatment with imiquimod and between responders and non responders10.1038/s41598-021-88424-z2045-2322https://doaj.org/article/6bb5791204724714b50998aaf52add662021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88424-zhttps://doaj.org/toc/2045-2322Abstract The presence of actinic keratoses (AKs) increases a patient’s risk of developing squamous cell carcinoma by greater than six-fold. We evaluated the effect of topical treatment with imiquimod on the tumor microenvironment by measuring transcriptomic differences in AKs before and after treatment with imiquimod 3.75%. Biopsies were collected prospectively from 21 patients and examined histologically. RNA was extracted and transcriptomic analyses of 788 genes were performed using the nanoString assay. Imiquimod decreased number of AKs by study endpoint at week 14 (p < 0.0001). Post-imiquimod therapy, levels of CDK1, CXCL13, IL1B, GADPH, TTK, ILF3, EWSR1, BIRC5, PLAUR, ISG20, and C1QBP were significantly lower (adjusted p < 0.05). Complete responders (CR) exhibited a distinct pattern of inflammatory gene expression pre-treatment relative to incomplete responders (IR), with alterations in 15 inflammatory pathways (p < 0.05) reflecting differential expression of 103 genes (p < 0.05). Presence of adverse effects was associated with improved treatment response. Differences in gene expression were found between pre-treatment samples in CR versus IR, suggesting that higher levels of inflammation pre-treament may play a part in regression of AKs. Further characterization of the immune micro-environment in AKs may help develop biomarkers predictive of response to topical immune modulators and may guide therapy.Megan H. TragerEmanuelle RizkSharon RoseKuixi ZhuBranden LauBenjamin T. FullertonJaya PradhanMichael MooreAyush C. SrivastavaGiselle SingerRobyn GartrellRui ChangLarisa J. GeskinYvonne M. SaengerGary GoldenbergNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Megan H. Trager Emanuelle Rizk Sharon Rose Kuixi Zhu Branden Lau Benjamin T. Fullerton Jaya Pradhan Michael Moore Ayush C. Srivastava Giselle Singer Robyn Gartrell Rui Chang Larisa J. Geskin Yvonne M. Saenger Gary Goldenberg Transcriptomic analysis identifies differences in gene expression in actinic keratoses after treatment with imiquimod and between responders and non responders
description	Abstract The presence of actinic keratoses (AKs) increases a patient’s risk of developing squamous cell carcinoma by greater than six-fold. We evaluated the effect of topical treatment with imiquimod on the tumor microenvironment by measuring transcriptomic differences in AKs before and after treatment with imiquimod 3.75%. Biopsies were collected prospectively from 21 patients and examined histologically. RNA was extracted and transcriptomic analyses of 788 genes were performed using the nanoString assay. Imiquimod decreased number of AKs by study endpoint at week 14 (p < 0.0001). Post-imiquimod therapy, levels of CDK1, CXCL13, IL1B, GADPH, TTK, ILF3, EWSR1, BIRC5, PLAUR, ISG20, and C1QBP were significantly lower (adjusted p < 0.05). Complete responders (CR) exhibited a distinct pattern of inflammatory gene expression pre-treatment relative to incomplete responders (IR), with alterations in 15 inflammatory pathways (p < 0.05) reflecting differential expression of 103 genes (p < 0.05). Presence of adverse effects was associated with improved treatment response. Differences in gene expression were found between pre-treatment samples in CR versus IR, suggesting that higher levels of inflammation pre-treament may play a part in regression of AKs. Further characterization of the immune micro-environment in AKs may help develop biomarkers predictive of response to topical immune modulators and may guide therapy.
format	article
author	Megan H. Trager Emanuelle Rizk Sharon Rose Kuixi Zhu Branden Lau Benjamin T. Fullerton Jaya Pradhan Michael Moore Ayush C. Srivastava Giselle Singer Robyn Gartrell Rui Chang Larisa J. Geskin Yvonne M. Saenger Gary Goldenberg
author_facet	Megan H. Trager Emanuelle Rizk Sharon Rose Kuixi Zhu Branden Lau Benjamin T. Fullerton Jaya Pradhan Michael Moore Ayush C. Srivastava Giselle Singer Robyn Gartrell Rui Chang Larisa J. Geskin Yvonne M. Saenger Gary Goldenberg
author_sort	Megan H. Trager
title	Transcriptomic analysis identifies differences in gene expression in actinic keratoses after treatment with imiquimod and between responders and non responders
title_short	Transcriptomic analysis identifies differences in gene expression in actinic keratoses after treatment with imiquimod and between responders and non responders
title_full	Transcriptomic analysis identifies differences in gene expression in actinic keratoses after treatment with imiquimod and between responders and non responders
title_fullStr	Transcriptomic analysis identifies differences in gene expression in actinic keratoses after treatment with imiquimod and between responders and non responders
title_full_unstemmed	Transcriptomic analysis identifies differences in gene expression in actinic keratoses after treatment with imiquimod and between responders and non responders
title_sort	transcriptomic analysis identifies differences in gene expression in actinic keratoses after treatment with imiquimod and between responders and non responders
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/6bb5791204724714b50998aaf52add66
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Transcriptomic analysis identifies differences in gene expression in actinic keratoses after treatment with imiquimod and between responders and non responders

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