Functional profiles of curatively treated adenoid cystic carcinoma unveil prognostic features and potentially targetable pathways
© 2023. The Author(s)..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
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| Enthalten in: |
Scientific reports - 13(2023), 1 vom: 31. Jan., Seite 1809 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Romani, Chiara [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 02.02.2023 Date Revised 16.03.2023 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41598-023-28901-9 |
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| Förderinstitution / Projekttitel: |
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NLM352313137 |
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| 520 | |a 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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| 700 | 1 | |a Bignotti, Eliana |e verfasserin |4 aut | |
| 700 | 1 | |a Tomasoni, Michele |e verfasserin |4 aut | |
| 700 | 1 | |a Ardighieri, Laura |e verfasserin |4 aut | |
| 700 | 1 | |a Bugatti, Mattia |e verfasserin |4 aut | |
| 700 | 1 | |a Battocchio, Simonetta |e verfasserin |4 aut | |
| 700 | 1 | |a Ravaggi, Antonella |e verfasserin |4 aut | |
| 700 | 1 | |a Tomasini, Davide |e verfasserin |4 aut | |
| 700 | 1 | |a Ravanelli, Marco |e verfasserin |4 aut | |
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| 700 | 1 | |a Piazza, Cesare |e verfasserin |4 aut | |
| 700 | 1 | |a Bossi, Paolo |e verfasserin |4 aut | |
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