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Functional profiles of curatively treated adenoid cystic carcinoma unveil prognostic features and potentially targetable pathways

Adenoid cystic carcinoma (ACC) of salivary gland is a slowly growing tumor showing a propensity for delayed recurrence, with decreased survival rates. The identification of poor prognosis patients may help in defining molecular-based targeted strategies in this rare disease orphan of new treatments....

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Autores principales: Romani, Chiara, Lorini, Luigi, Bozzola, Anna, Bignotti, Eliana, Tomasoni, Michele, Ardighieri, Laura, Bugatti, Mattia, Battocchio, Simonetta, Ravaggi, Antonella, Tomasini, Davide, Ravanelli, Marco, Gurizzan, Cristina, Lombardi, Davide, Mattavelli, Davide, Calza, Stefano, Piazza, Cesare, Bossi, Paolo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9889376/
https://www.ncbi.nlm.nih.gov/pubmed/36720951
http://dx.doi.org/10.1038/s41598-023-28901-9
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author Romani, Chiara
Lorini, Luigi
Bozzola, Anna
Bignotti, Eliana
Tomasoni, Michele
Ardighieri, Laura
Bugatti, Mattia
Battocchio, Simonetta
Ravaggi, Antonella
Tomasini, Davide
Ravanelli, Marco
Gurizzan, Cristina
Lombardi, Davide
Mattavelli, Davide
Calza, Stefano
Piazza, Cesare
Bossi, Paolo
author_facet Romani, Chiara
Lorini, Luigi
Bozzola, Anna
Bignotti, Eliana
Tomasoni, Michele
Ardighieri, Laura
Bugatti, Mattia
Battocchio, Simonetta
Ravaggi, Antonella
Tomasini, Davide
Ravanelli, Marco
Gurizzan, Cristina
Lombardi, Davide
Mattavelli, Davide
Calza, Stefano
Piazza, Cesare
Bossi, Paolo
author_sort Romani, Chiara
collection PubMed
description Adenoid cystic carcinoma (ACC) of salivary gland is a slowly growing tumor showing a propensity for delayed recurrence, with decreased survival rates. The identification of poor prognosis patients may help in defining molecular-based targeted strategies in this rare disease orphan of new treatments. Through a gene expression microarray-based approach followed by GSE functional analysis the expression profile of 46 primary untreated ACC samples and of ACC (h-TERT) tumor cells was analyzed. Patients who experienced early relapse showed enrichment in proliferation-related gene sets, including the G2-M checkpoint, E2F and myc targets, and in gene sets related to IFN signaling and aberrant proteostasis (FDR < 0.1), indicating increased mitotic and transcriptional activity in aggressive ACC. Similar functions were enriched in ACC samples classified by immunohistochemical staining as p63-negative, which exhibited increased protein burden and activation of pro-survival stress response pathways compared to p63-positive tumors. Compared to ACC tissues, ACC (h-TERT) cells share transcriptional features of aggressive p63-negative tumors. These data suggest association of specific pathway alterations with histopathological features of ACC, as recapitulated by p63 testing in patient prognostic stratification, anticipating new avenues for therapeutic intervention.
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spelling pubmed-98893762023-02-02 Functional profiles of curatively treated adenoid cystic carcinoma unveil prognostic features and potentially targetable pathways Romani, Chiara Lorini, Luigi Bozzola, Anna Bignotti, Eliana Tomasoni, Michele Ardighieri, Laura Bugatti, Mattia Battocchio, Simonetta Ravaggi, Antonella Tomasini, Davide Ravanelli, Marco Gurizzan, Cristina Lombardi, Davide Mattavelli, Davide Calza, Stefano Piazza, Cesare Bossi, Paolo Sci Rep Article Adenoid cystic carcinoma (ACC) of salivary gland is a slowly growing tumor showing a propensity for delayed recurrence, with decreased survival rates. The identification of poor prognosis patients may help in defining molecular-based targeted strategies in this rare disease orphan of new treatments. Through a gene expression microarray-based approach followed by GSE functional analysis the expression profile of 46 primary untreated ACC samples and of ACC (h-TERT) tumor cells was analyzed. Patients who experienced early relapse showed enrichment in proliferation-related gene sets, including the G2-M checkpoint, E2F and myc targets, and in gene sets related to IFN signaling and aberrant proteostasis (FDR < 0.1), indicating increased mitotic and transcriptional activity in aggressive ACC. Similar functions were enriched in ACC samples classified by immunohistochemical staining as p63-negative, which exhibited increased protein burden and activation of pro-survival stress response pathways compared to p63-positive tumors. Compared to ACC tissues, ACC (h-TERT) cells share transcriptional features of aggressive p63-negative tumors. These data suggest association of specific pathway alterations with histopathological features of ACC, as recapitulated by p63 testing in patient prognostic stratification, anticipating new avenues for therapeutic intervention. Nature Publishing Group UK 2023-01-31 /pmc/articles/PMC9889376/ /pubmed/36720951 http://dx.doi.org/10.1038/s41598-023-28901-9 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Romani, Chiara
Lorini, Luigi
Bozzola, Anna
Bignotti, Eliana
Tomasoni, Michele
Ardighieri, Laura
Bugatti, Mattia
Battocchio, Simonetta
Ravaggi, Antonella
Tomasini, Davide
Ravanelli, Marco
Gurizzan, Cristina
Lombardi, Davide
Mattavelli, Davide
Calza, Stefano
Piazza, Cesare
Bossi, Paolo
Functional profiles of curatively treated adenoid cystic carcinoma unveil prognostic features and potentially targetable pathways
title Functional profiles of curatively treated adenoid cystic carcinoma unveil prognostic features and potentially targetable pathways
title_full Functional profiles of curatively treated adenoid cystic carcinoma unveil prognostic features and potentially targetable pathways
title_fullStr Functional profiles of curatively treated adenoid cystic carcinoma unveil prognostic features and potentially targetable pathways
title_full_unstemmed Functional profiles of curatively treated adenoid cystic carcinoma unveil prognostic features and potentially targetable pathways
title_short Functional profiles of curatively treated adenoid cystic carcinoma unveil prognostic features and potentially targetable pathways
title_sort functional profiles of curatively treated adenoid cystic carcinoma unveil prognostic features and potentially targetable pathways
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9889376/
https://www.ncbi.nlm.nih.gov/pubmed/36720951
http://dx.doi.org/10.1038/s41598-023-28901-9
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