Spexin (SPX), enkurin, reelin, and DARS2 as candidate tissue biomarkers to distinguish benign and malignant gastroenteropancreatic neuroendocrine neoplasms and differentiate NET grades

Neuroendocrine neoplasms (NENs) comprise a morphologically and clinically heterogeneous family of tumors that arise from neuroendocrine cells distributed across multiple organ systems. Histologically, NENs are categorized into well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs), and graded primarily by mitotic activity and Ki-67 index [1,2]. All of these neoplasms are characterized by the expression of general neuroendocrine markers and the production of peptide hormones and/or biogenic amines, as illustrated in (Fig.