Identifying Drug Candidates for Pancreatic Neuroendocrine Tumors Based on Differently Expressed Genes

Abstract

Introduction: Prognosis of patients with pancreatic neuroendocrine tumors(pNET) is variable and there is a paucity of effective drugs to treat pNET. Genome-wide analyses may allow for identification of potential drugs based on differentially expressed genes(DEGs). Methods: Oligo microarray data from RNA expression profiling of pNET and normal pancreas tissues was downloaded from the Gene Expression Omnibus. Functional and pathway enrichment information of the DEGs was obtained using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. Corresponding homologous proteins were analyzed and potential therapeutic drugs for pNET were identified using the Connectivity Map and Drug-Gene Interaction Database. Results: RNA expression information from 63 non-functional pNET samples and 9 normal pancreatic tissue samples was obtained. Assessment of raw data from 12,610 genes demonstrated that 1,082 and 380 genes were upregulated and downregulated, respectively. Of note, tumor and normal tissue had different expression profiles(Figure). Upregulated pathways were associated with nitrogen metabolism, GABAergic synapse and graft-versus-host disease, whereas downregulated pathways include C-type leptin receptor signaling pathway, pertussis and AMPK signaling pathway. In particular, upregulated genes included DYNLL1, GNB5, GNB2, GNG4, GNAI2, GNAI1, HIST2H2BE, NUP107, NUP133 and SNAP25, while downregulated genes include CXCL8, F2, CXCL2, GCG, SST, INS, GALR3, CCL20, ADRA2B and CXCL6. Using the Drug-Gene Interaction Database, candidate drugs for pNET treatment included canertinib, acarbose, AG-592, lonidamine, azacytidine, erlotinib, rottlerin and HU-211. Conclusions: Drug candidates targeted against pNET were identified based on differentially expressed genes. Available genetic atlas data may help identify agents with therapeutic efficacy to treat pNET patients using a more targeted approach.