Frontiers in Oncology (Jul 2020)

Altered miRNAs Expression Correlates With Gastroenteropancreatic Neuroendocrine Tumors Grades

  • Elisabetta Cavalcanti,
  • Vanessa Galleggiante,
  • Sergio Coletta,
  • Elisa Stasi,
  • Marcello Chieppa,
  • Raffaele Armentano,
  • Grazia Serino

DOI
https://doi.org/10.3389/fonc.2020.01187
Journal volume & issue
Vol. 10

Abstract

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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.

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