microRNA profiling in different grading of gastroenteropancreatic neuroendocrine tumors (GEP-NETs)

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare and heterogeneous tumors presenting a wide spectrum of different clinical and biological characteristics. In these tumors, the histological evaluation is a crucial element of clinical management. Currently, tumor grading, determined by Ki-67 staining and mitotic counts, is the most reliable predictor of prognosis. This scoring method is time-consuming and a high reproducibility cannot be achieved. Novel approaches are needed to support histological evaluation and prognosis. In this study, starting from a microarray analysis, we defined the miRNAs signature for poorly differentiated NETs (G3) compared to well differentiated NETs (G1 and G2) consisting of 56 deregulated miRNAs. Moreover, we identified 8 miRNAs that were expressed in all GEP-NETs grades but at different level. Among these miRNAs, we found miR-96-5p that raised its expression levels from grade 1 to grade 3; inversely, its target FOXO1 was decrease from grade 1 to grade 3. Our results reveal that the miRNAs expression profile of GEP-NET correlates their expression with grading showing a potential advantage of miRNA quantification to aid clinicians in the classification of common GEP-NETs subtypes. Global miRNA expression profiles of 18 GEP-NETs patients divided in 7 G1, 5 G2 and 6 G3 were determined by miRNA microarray.