학술논문
Functional profiles of curatively treated adenoid cystic carcinoma unveil prognostic features and potentially targetable pathways.
Document Type
Article
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
Source
Subject
*ADENOID cystic carcinoma
*IMMUNOSTAINING
*GENE expression
*SALIVARY glands
*RARE diseases
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Language
ISSN
2045-2322
Abstract
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. [ABSTRACT FROM AUTHOR]