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Pan-Cancer Analysis Reveals That E1A Binding Protein p300 Mutations Increase Genome Instability and Antitumor Immunity

E1A binding protein p300 (EP300) is mutated in diverse cancers. Nevertheless, a systematic investigation into the associations of EP300 mutations with genome instability and antitumor immunity in pan-cancer remains lacking. Using the datasets from The Cancer Genome Atlas, we analyzed the correlation...

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Autores principales: Chen, Zuobing, Chen, Canping, Li, Lin, Zhang, Tianfang, Wang, Xiaosheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8488206/
https://www.ncbi.nlm.nih.gov/pubmed/34616736
http://dx.doi.org/10.3389/fcell.2021.729927
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author Chen, Zuobing
Chen, Canping
Li, Lin
Zhang, Tianfang
Wang, Xiaosheng
author_facet Chen, Zuobing
Chen, Canping
Li, Lin
Zhang, Tianfang
Wang, Xiaosheng
author_sort Chen, Zuobing
collection PubMed
description E1A binding protein p300 (EP300) is mutated in diverse cancers. Nevertheless, a systematic investigation into the associations of EP300 mutations with genome instability and antitumor immunity in pan-cancer remains lacking. Using the datasets from The Cancer Genome Atlas, we analyzed the correlations between EP300 mutations and genome instability and antitumor immune response in 11 cancer types. Compared to EP300-wild-type cancers, EP300-mutated cancers had significantly higher tumor mutation burden (TMB) in 10 cancer types. EP300-mutated cancers harbored a much higher fraction of microsatellite instable cancers in the colon and gastric cancers. EP300 was co-mutated with genes involved in DNA damage repair pathways in multiple cancers. Furthermore, compared to EP300-wild-type cancers, EP300-mutated cancers had significantly higher immune cytolytic activity scores and ratios of immune-stimulatory over immune-inhibitory signatures in diverse cancers. Also, EP300-mutated cancers showed significantly higher programmed death-ligand 1 (PD-L1) expression levels than EP300-wild-type cancers. The increased TMB, antitumor immune activity, and PD-L1 expression indicated a favorable response to immune checkpoint inhibitors (ICIs) in EP300-mutated cancers, as evident in three cancer cohorts treated with ICIs. Thus, the EP300 mutation could be a predictive biomarker for the response to immunotherapy.
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spelling pubmed-84882062021-10-05 Pan-Cancer Analysis Reveals That E1A Binding Protein p300 Mutations Increase Genome Instability and Antitumor Immunity Chen, Zuobing Chen, Canping Li, Lin Zhang, Tianfang Wang, Xiaosheng Front Cell Dev Biol Cell and Developmental Biology E1A binding protein p300 (EP300) is mutated in diverse cancers. Nevertheless, a systematic investigation into the associations of EP300 mutations with genome instability and antitumor immunity in pan-cancer remains lacking. Using the datasets from The Cancer Genome Atlas, we analyzed the correlations between EP300 mutations and genome instability and antitumor immune response in 11 cancer types. Compared to EP300-wild-type cancers, EP300-mutated cancers had significantly higher tumor mutation burden (TMB) in 10 cancer types. EP300-mutated cancers harbored a much higher fraction of microsatellite instable cancers in the colon and gastric cancers. EP300 was co-mutated with genes involved in DNA damage repair pathways in multiple cancers. Furthermore, compared to EP300-wild-type cancers, EP300-mutated cancers had significantly higher immune cytolytic activity scores and ratios of immune-stimulatory over immune-inhibitory signatures in diverse cancers. Also, EP300-mutated cancers showed significantly higher programmed death-ligand 1 (PD-L1) expression levels than EP300-wild-type cancers. The increased TMB, antitumor immune activity, and PD-L1 expression indicated a favorable response to immune checkpoint inhibitors (ICIs) in EP300-mutated cancers, as evident in three cancer cohorts treated with ICIs. Thus, the EP300 mutation could be a predictive biomarker for the response to immunotherapy. Frontiers Media S.A. 2021-09-20 /pmc/articles/PMC8488206/ /pubmed/34616736 http://dx.doi.org/10.3389/fcell.2021.729927 Text en Copyright © 2021 Chen, Chen, Li, Zhang and Wang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Chen, Zuobing
Chen, Canping
Li, Lin
Zhang, Tianfang
Wang, Xiaosheng
Pan-Cancer Analysis Reveals That E1A Binding Protein p300 Mutations Increase Genome Instability and Antitumor Immunity
title Pan-Cancer Analysis Reveals That E1A Binding Protein p300 Mutations Increase Genome Instability and Antitumor Immunity
title_full Pan-Cancer Analysis Reveals That E1A Binding Protein p300 Mutations Increase Genome Instability and Antitumor Immunity
title_fullStr Pan-Cancer Analysis Reveals That E1A Binding Protein p300 Mutations Increase Genome Instability and Antitumor Immunity
title_full_unstemmed Pan-Cancer Analysis Reveals That E1A Binding Protein p300 Mutations Increase Genome Instability and Antitumor Immunity
title_short Pan-Cancer Analysis Reveals That E1A Binding Protein p300 Mutations Increase Genome Instability and Antitumor Immunity
title_sort pan-cancer analysis reveals that e1a binding protein p300 mutations increase genome instability and antitumor immunity
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8488206/
https://www.ncbi.nlm.nih.gov/pubmed/34616736
http://dx.doi.org/10.3389/fcell.2021.729927
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