Microarray based analysis of gene expression patterns in pancreatic neuroendocrine tumors.

OBJECTIVE: Pancreatic neuroendocrine tumors (PanNETs) are a small subgroup of tumors with a variety of biological behaviors.

MATERIALS AND METHODS: We sought to identify the specially expressed genes and characterize significant pathways in PanNETs compared with non-neoplastic samples. Gene expression profile GSE43795 was obtained from Gene Expression Omnibus database, which included 6 PanNETs and 5 non-neoplastic samples. The differentially expressed genes (DEGs) were identified using Limma package. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to enrich the functions and pathways of DEGs. Transcription factors (TFs) and tumor-associated genes (TAGs) were also identified. Finally, a protein-protein interaction (PPI) network was constructed, and hub proteins and functional module were screened out.

RESULTS: Total of 821 DEGs (421 down-regulated, 400 up-regulated) were selected. GO and KEGG enrichment analyses showed that up-regulated DEGs were related to several pathways, including type 2 diabetes mellitus, Ca2+ signaling pathway, long-term potentiation, and long-term depression pathways. Down-regulated DEGs were enriched in several pathways, such as pancreatic secretion, protein digestion and absorption, and metabolic pathway. Interferon-stimulated gene protein 15 (ISG15), somatostatin (SST), and synaptosomal-associated protein 25 kDa (SNAP25) were identified as hub proteins.

CONCLUSIONS: The genes involved in type 2 diabetes mellitus pathway may play important roles in the development of PanNETs. SNAP25, SST, and ISG15 may be used as potential targets for treatment of PanNETs.