TY - JOUR
T1 - Altered miRNAs Expression Correlates With Gastroenteropancreatic Neuroendocrine Tumors Grades
AU - Cavalcanti, Elisabetta
AU - Galleggiante, Vanessa
AU - Coletta, Sergio
AU - Stasi, Elisa
AU - Chieppa, Marcello
AU - Armentano, Raffaele
AU - Serino, Grazia
N1 - Funding Information:
We thank Mary V.C. Pragnell, B.A. for language revision of the manuscript. Funding. This work was supported by grants from the Italian Ministry of Health (GR-2011-02350438 and Ricerca Corrente n? 12 and 15/2019) and Apulia Region grant SI-CURA (KC3U5Y1).
Publisher Copyright:
© Copyright © 2020 Cavalcanti, Galleggiante, Coletta, Stasi, Chieppa, Armentano and Serino.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/7/17
Y1 - 2020/7/17
N2 - Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare and heterogeneous tumors that present a wide spectrum of different clinical and biological characteristics. Currently, tumor grading, determined by Ki-67 staining and mitotic counts, represents the most reliable predictor of prognosis. This time-consuming approach fails to reach high reproducibility standards thus requiring novel approaches to support histological evaluation and prognosis. In this study, starting from a microarray analysis of paraffin-embedded tissue specimens, we defined the miRNAs signature for poorly differentiated NETs (G3) compared to well-differentiated NETs (G1 and G2) consisting of 56 deregulated miRNAs. We identified 8 miRNAs that were expressed in all GEP-NETs grades but at different level. Among these miRNAs, miR-96-5p expression level was progressively higher from grade 1 to grade 3; inversely, its target FoxO1 expression decreased from grade 1 to grade 3. Our results reveal that the miRNAs expression profile of GEP-NET is correlated with the tumor grade, showing a potential advantage of miRNA quantification that could aid clinicians in the classification of common GEP-NETs subtypes. These findings could reliably support the histological evaluation of GEP-NETs paving the way toward personalized treatment approaches.
AB - Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare and heterogeneous tumors that present a wide spectrum of different clinical and biological characteristics. Currently, tumor grading, determined by Ki-67 staining and mitotic counts, represents the most reliable predictor of prognosis. This time-consuming approach fails to reach high reproducibility standards thus requiring novel approaches to support histological evaluation and prognosis. In this study, starting from a microarray analysis of paraffin-embedded tissue specimens, we defined the miRNAs signature for poorly differentiated NETs (G3) compared to well-differentiated NETs (G1 and G2) consisting of 56 deregulated miRNAs. We identified 8 miRNAs that were expressed in all GEP-NETs grades but at different level. Among these miRNAs, miR-96-5p expression level was progressively higher from grade 1 to grade 3; inversely, its target FoxO1 expression decreased from grade 1 to grade 3. Our results reveal that the miRNAs expression profile of GEP-NET is correlated with the tumor grade, showing a potential advantage of miRNA quantification that could aid clinicians in the classification of common GEP-NETs subtypes. These findings could reliably support the histological evaluation of GEP-NETs paving the way toward personalized treatment approaches.
KW - FoXO1
KW - gastrointestinal tract
KW - miR-96-5p
KW - miRNAs
KW - molecular markers
KW - neuroendocrine tumors
KW - tumor grading
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U2 - 10.3389/fonc.2020.01187
DO - 10.3389/fonc.2020.01187
M3 - Article
AN - SCOPUS:85088516422
VL - 10
JO - Frontiers in Oncology
JF - Frontiers in Oncology
SN - 2234-943X
M1 - 1187
ER -