ObjectiveTo explore the key genes and potential molecular mechanisms of liver and lymph node metastases relevant to duodenal neuroendocrine tumors (DNET). MethodsThe tissues of paracancerous duodenal epithelial, primary lesion, liver metastasis lesion, and lymph node metastasis lesion of a rare DNET accompanied by liver and lymph node metastases were sequenced and analyzed. The differentially expressed genes (DEGs) were screened for different tissues and the functional enrichment analysis was performed. ResultsThe tissues of paracancerous duodenal epithelial was used as the control, a total of 2 053 DEGs expressed only in the liver metastases lesion tissues and 742 DEGs expressed only in the lymph node metastases lesion tissues were screened out, and the top 5 genes expressed in the liver metastases lesion tissues were ORM1, C4BPA, AHSG, C9, and LBP, which in the lymph node metastases lesion tissues were ABHD12B, AC100850.1, HOXC9, AC083967.1, and HOXC8. Kyoto Encyclopedia of Genes and Genomes enrichment analysis found that the DEGs were mainly enriched in the phosphatidylinosiol 3 kinase / protein kinase B pathway, mitogen-activated protein kinase pathway, human papillomavirus infection, etc. ConclusionMultiple DEGs and pathways in metastatic lesions are found in this patient with DNET accompanied by liver metastasis and lymph node metastasis, which provides a new direction for treatment and prophylaxis of DNET.