MicroRNA analysis of gastroenteropancreatic neuroendocrine tumors and metastases
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Nadine Zimmermann1,*, Juliana Knief1,*, Tim Kacprowski2,*, Pamela Lazar-Karsten1, Tobias Keck3, Franck Billmann3, Sebastian Schmid4, Kim Luley4, Hendrik Lehnert4, Georg Brabant4,* and Christoph Thorns1,*
1Department of Pathology, Section of Hematopathology and Endocrine Pathology, University Hospital of Schleswig-Holstein, Lübeck 23538, Germany
2Department of Functional Genomics, Interfaculty Institute of Genetics and Functional Genomics, University Medicine Greifswald, Greifswald 17475, Germany
3Department of Surgery, University Hospital of Schleswig-Holstein, Lübeck 23538, Germany
4Department of Internal Medicine 1, University Hospital of Schleswig-Holstein, Lübeck 23538, Germany
*These authors contributed equally to this work
Juliana Knief, email: [email protected]
Keywords: gastroenteropancreatic tumors; neuroendocrine neoplasias; microRNA; metastatic disease
Received: March 22, 2018 Accepted: April 24, 2018 Published: June 19, 2018
The incidence of neuroendocrine neoplasias (NEN) continues to increase. Since the primary tumor cannot be diagnosed in some cases of metastatic disease, new biomarkers are clearly needed to find the most probable site of origin. Tissue samples from 79 patients were analyzed and microRNA profiles were generated from a total of 76 primary tumors, 31 lymph node and 14 solid organ metastases. NEN metastases were associated with elevated levels of miR-30a-5p, miR-210, miR-339-3p, miR-345 and miR-660. Three microRNAs showed a strong correlation between proliferation index and metastatic disease in general (miR-150, miR-21 and miR-660). Further, each anatomic location (primary or metastatic) had one or more site-specific microRNAs more highly expressed in these tissues. Comparison between primary tumors and metastases revealed an overlap only in pancreatic (miR-127) and ileal tumors (let-7g, miR-200a and miR-331). This thorough analysis of gastroenteropancreatic neuroendocrine tumors demonstrates site-specific microRNA profiles, correlation with proliferation indices as well as corresponding nodal and distant metastases. Using microRNA profiling might improve NEN diagnostics by linking metastases to a most probable site of origin.
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