EVs are involved in local and distant intercellular communication and play a vital role in cancer development. Since EVs have been found in almost all body fluids, there are currently active attempts for their application in liquid diagnostics. Blood is the most commonly used source of EVs for the screening of cancer markers, although the percentage of tumor-derived EVs in the blood is extremely low. In contrast, GJ, as a local biofluid, is expected to be enriched with GC-associated EVs. However, EVs from GJ have never been applied for the screening and are underinvestigated overall. Here we show that EVs can be isolated from GJ by ultracentrifugation. TEM analysis showed high heterogeneity of GJ-derived EVs, including those with exosome-like size and morphology. In addition to morphological diversity, EVs from individual GJ samples differed in the composition of exosomal markers. We also show the presence of stomatin within GJ-derived EVs for the first time. The first conducted comparison of miRNA content in EVs from GC patients and healthy donors performed using a pilot sampling revealed the significant differences in several miRNAs (-135b-3p, -199a-3p, -451a). These results demonstrate the feasibility of the application of GJ-derived EVs for screening for miRNA GC markers.

Neuroendocrine neoplasms (NENs) are a heterogeneous group of rare epithelial tumors that arise from cells with a neuroendocrine phenotype. NENs are found in the gastrointestinal tract and pancreas – 60 % of all localities. The incidence of gastric NENs is about 9 % of all neuroendocrine tumors of the gastrointestinal tract and 0.3 % of all stomach tumors. Stomach neuroendocrine tumors (NETs) are classified into three clinico-pathological types, based on etiology, pathogenesis and morphology. There are also separate neuroendocrine cancers: small- and large-cell. The prognosis and approach to treatment of various types of gastric NENs differs significantly. Modern methods of instrumental diagnostics, immunohistochemical methods of morphological research, along with light microscopy, do not always allow us to accurately assess the malignant potential of a tumor and individualize the treatment process. One of the promising directions in the study of NETs is to determine the molecular mechanism underlying their development, in particular the role of microRNAs. This direction can open a new vector of understanding the pathogenesis, determining the prognosis of the disease, as well as finding new application points for the drug treatment of NETs. MicroRNAs are a class of short non-coding RNA molecules (18–25 nucleotides). MicroRNAs can be involved in the regulation of all major cellular processes, including proliferation and differentiation, metabolism, signaling pathways, and apoptosis. A study of microRNA expression in tissues revealed tumor-specific microRNAs. In contrast to a number of other malignant tumors, microRNA expression in patients diagnosed with NENs is poorly understood. MicroRNA-222 and microRNA-202 are among the few microRNAs that have been demonstrated in the NETs of the stomach.

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From the latest WHO classification of neuroendocrine neoplasms (NENs), the term MiNENs refers to mixed neuroendocrinenon-neuroendocrine tumors. A neuroendocrine component coexists with a non-neuroendocrine one in them. They are morphologically and/or immunohistochemically validated. The non-neuroendocrine component implicates adenocarcinoma, apart from other histological subtypes of carcinomas, such as squamous cell carcinoma. The neuroendocrine component can be represented by a high-grade tumour (HGNEC) in addition to neuroendocrine cancer. Gastric NENs also have subgroups of MiNENs such as mixed adenoneuroendocrine carcinoma (Mixed-adenocarcinoma-NEC), which includes both, small or large cell type, neuroendocrine carcinoma (NEC) and mixed adenoneuroendocrine tumor (Mixed-adenocarcinoma-NET). Mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) is a rare disease. Based on the available data, neuroendocrine component has a highly aggressive biological behaviour represented by a low-differentiated neuroendocrine tumor in the majority of MiNENs cases. The treatment is based on the principles of neuroendocrine tumour therapy. The foregoing shows that it is not possible to provide precise epidemiological data, prognosis and approve treatment strategies.

Neuroendocrine tumors (NETs) of the stomach include a wide range of neoplasm with different variants of the disease, various approaches to the treatment and different prognosis. The incidence is quite low - NETs of stomach accounted for only 9% of all gastrointestinal (GI) NETs and 0,3% of all tumors of stomach. Gastric NETs have significantly different biological and clinical characteristics from other carcinoids developing from “foregut”. The distinctive features of these tumors attract the attention of many scientists. Modern methods of instrumental diagnostics, as well as histological, immunohistochemical and molecular genetic, make it possible to assess malignant potential of the tumor and individualize treatment in every case. In this article we have tried to bring the information about NET with high and poor differentiation, which include small and large cell types together.