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The aim of the study was to compare RNA sequencing data of sporadic nonfunctioning pancreatic neuroendocrine neoplasms (PNENs) to identify gene expression patterns that may be important for molecular differentiation of tumor aggressiveness.RNA sequencing was performed on samples of sporadic nonfunctioning PNENs, grouped as tumors with mild behavior (nonmetastatic and Ki67 < 5%) or aggressive behavior (metastatic and Ki67 ≥ 5%), on an Illumina Genome Analyzer II platform. Bioinformatic analyses were performed on the resulting data.Of 22,810 identified transcripts from protein-coding genes, a set of 309 genes were significantly differentially expressed between the 2 groups, of which 166 were upregulated and 143 downregulated in the aggressive disease group. Among the top protein-coding upregulated genes, we found genes encoding proteins involved in DNA packaging, ability to taste, chromosome structuring, cytoskeleton structuring, and cell-cell signaling. Among the top protein-coding downregulated genes, we found genes encoding proteins involved in neuronal differentiation, cytoskeleton structuring, cell-cell signaling, and immunological processes.A higher degree of tumor aggressiveness in sporadic nonfunctioning PNENs seems to be associated with upregulation of genes involved in regulation of the cell cycle and cell division. Small sample size and lack of a replication set are limitations of this study.