Abstract
Small intestinal neuroendocrine tumors (SI-NETs) remain the most common subset in gastrointestinal neuroendocrine tumors and featured by aggressiveness. However, the molecular feature of SI-NETs remains largely unclear with key genes and pathways yet to be identified. The gene expression profile GSE65286 was retrieved for analysis. Artificial neural networks (ANNs) were constructed for the hub genes network models. A total of 613 differentially expressed genes (DEGs) were identified between normal (N) and primary tumor (T) groups, whereas 61 DEGs were identified between T and liver metastases (LM) groups. The top Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways for the DEGs of N versus T were fat digestion and absorption pathway. For T versus LM the top KEGG pathways were complement and coagulation. In gene set enrichment analysis (GSEA), five gene sets, including Notch signaling, inflammatory response, coagulation, KRAS signaling, and allograft rejection were significantly enriched in the T group. The hub genes in the DEGs of T versus LM included albumin, fibrinogen gamma chain, alpha 2-HS glycoprotein, transferrin and GC, vitamin D binding protein. A distinct correlational alteration of hub genes was observed between T and LM groups. In ANN analysis, ALB and TF were the top predictors of metastasis. Moreover, the expression of ALB≤ showed the highest support to T whereas ALB>15.97 supports LM. TF≤7.54 showed the highest negative correlation to the T. This bioinformatics analysis provided insights on potential key pathways and genes networks involved in SI-NETs and established an ANN-based hub gene model for metastatic prediction.
Highlights
Neuroendocrine tumors (NETs) were initially described by Oberndofer using karzinoid in 1907 and mostly arise from the neuroendocrine cells with the ability to generate hormonal-related peptides [1,2]
During the last three decades, the incidence of small intestinal neuroendocrine tumor (SI-NET) has annually increased by 3.8% [4]
Given GSE65286 only contained 2 lymph nodes metastases (LN) samples, the comparison only performed in N (n = 10) versus T (n = 10) and T (n = 10) versus liver metastases (LM) (n = 21)
Summary
Neuroendocrine tumors (NETs) were initially described by Oberndofer using karzinoid (carcinoid) in 1907 and mostly arise from the neuroendocrine cells with the ability to generate hormonal-related peptides [1,2]. Small intestinal neuroendocrine tumors (SI-NETs), the most common subset in gastrointestinal neuroendocrine tumors, are featured by aggressiveness and therapy-resistance [1,3]. During the last three decades, the incidence of SI-NETs has annually increased by 3.8% [4]. The age-adjusted incidence of NETs (over 30 years old) in digestive system has dramatically increased by 720%, with 225% increasing in ileal part and 460% in small intestinal [4]. The five-year survival rate surprisingly remains unchanged [4]. SI-NET patients commonly are diagnosed as advanced stage at initial presentation due to indolent unnoticeable clinical course [1].
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