Prognostic relevance of proliferation-related miRNAs in pancreatic neuroendocrine neoplasms.

Objective Pancreatic neuroendocrine neoplasms (PanNENs) are rare tumors arising from the endocrine pancreas, however their prognosis differs significantly upon their proliferative state which is characterized by histopathological grading. MiRNAs are small, noncoding RNAs posttranscriptionally regulating gene expression. Our aim was to identify miRNAs with altered expression upon proliferation which can be used as prognostic biomarkers in PanNENs. Methods MiRNA expression profiles of 40 PanNENs were downloaded from Gene Expression Omnibus and were reanalyzed upon tumor grades (discovery cohort). Results of the reanalysis were confirmed by qRT-PCR analysis of 5 miRNAs on an independent validation cohort of sixty three primary PanNEN samples. Cox proportional hazards survival regression model was fit for both univariate and multivariate analysis to determine the miRNAs' effect on progression-free and overall survival. Results 19 miRNAs displayed differential expression between tumor grades. The altered expression of 3 out of 5 chosen miRNAs was successfully validated; hsa-miR-21, hsa-miR-10a and hsa-miR-106b were up-regulated in more proliferative PanNENs compared to grade 1 tumors. In univariate analysis, higher expression of tissue hsa-miR-21, hsa-miR-10a and hsa-miR-106b expression of primary PanNENs predicted worse progression-free and overall survival, however multivariate analysis only confirmed the expression of hsa-miR-21 as an independent prognostic factor. Conclusions The expression of hsa-miR-106b, hsa-miR-10a and especially hsa-miR-21 has prognostic relevance regarding progression-free and overall survival in patients with PanNENs.