AUTHOR=Cavalcanti Elisabetta , Galleggiante Vanessa , Coletta Sergio , Stasi Elisa , Chieppa Marcello , Armentano Raffaele , Serino Grazia TITLE=Altered miRNAs Expression Correlates With Gastroenteropancreatic Neuroendocrine Tumors Grades JOURNAL=Frontiers in Oncology VOLUME=10 YEAR=2020 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.01187 DOI=10.3389/fonc.2020.01187 ISSN=2234-943X ABSTRACT=

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.