Abstract
Gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs) are rare diseases occurring in the gastrointestinal tract and pancreas. They are characterized by the loss of epithelial tubular gland elements, and by the increased expression of neuroendocrine markers. GEP-NENs are subdivided into two histo-pathological types, gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) and gastro-entero-pancreatic neuroendocrine carcinomas (GEP-NECs). According to WHO 2017 and 2019 classification criteria are graded and staged in four categories, NET-G1, NET-G2, NET-G3, and NEC-G3. The molecular characterization of these tumors can be fundamental for the identification of new diagnostic, prognostic and predictive biomarkers. The main purpose of this study was to analyze the expression of the paralogous 13 HOX genes, normally involved in embryogenic development and frequently deregulated in human cancers, and of the HOX regulating lncRNA HOTAIR in GEP-NENs. The expression of HOX genes is gradually lost in the transition from GEP NET G1 to NET/NEC G3 tumors, while HOTAIR expression, inversely correlated with HOX genes expression and weakly expressed in low-grade GEP NENs, becomes aberrant in NET G3 and NEC G3 categories. Our data highlights their potential role in the molecular stratification of GEP-NENs by suggesting new prognostic markers and potential therapeutic targets.
Highlights
Since the de-regulation posterior genes of the HOX genes network has been recently described in some tumors with neuroendocrine differentiation [18], in this study we aimed to investigate the role of the paralogous group 13 HOX genes in a case series of GEP-NEN patients
We evaluated the role of lncRNA HOTAIR, a regulator of posterior
The incidence of GEP-NENs has increased over the last few decades
Summary
Neuroendocrine neoplasms are a heterogeneous group of rare tumors that can arise from different anatomic sites including foregut, midgut, hindgut, lung, bladder, prostate, adrenal gland and sympathetic nervous organs [1]. Tumors arising from gastrointestinal tract, defined Gastro-entero-pancreatic neuroendocrine tumors (GEP-NET) account for two-thirds of NENs. The World Health Organization (WHO) 2017 (for Pancreatic neuroendocrine neoplasms [3] and 2019 (for gasto-enteric neuroendocrine neoplasms) [4] histopathological classification, introducing as classifying criteria tumor grading and cell differentiation, identified four categories for GEP-NEN tumors: (i) well-differentiated Neuroendocrine tumors, grade 1 (NET-G1); (ii) well-differentiated Neuroendocrine tumor, grade 2 (NETG2); (iii) high proliferating well-differentiated Neuroendocrine tumor, grade 3 (NET-G3);
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