The Impact of miR-21-5p, miR-145-5p and miR-382-5p Expression in Gastric Adenocarcinoma Cells on Lymphatic Spread Capability

<b>Objectives</b>: <i>miR-21-5p</i>, <i>miR-145-5p</i> and <i>miR-382-5p</i> have been associated with angiogenesis, which plays a central role in tumor growth and metastasis formation. The aim of the study was to determine whether expression of these three potentially angiogenic miRNAs is related to the lymphatic spread capability of gastric adenocarcinoma and patient survival. <b>Methods</b>: Pathoclinical data of 123 patients who underwent elective gastric resection for adenocarcinoma between 1 August 2006 and 31 December 2013 were retrospectively retrieved. The major concerns were the total number of lymph nodes retrieved, the number of positive nodes, depth of the tumor invasion to the stomach wall, pTNM stage of the disease, Lauren histological tumor type, presence of a mucinous component in the cancer tissue, tumor location in the stomach and survival outcome. The cancer tissues of patients were examined for the expression levels of <i>miR-21-5p</i>, <i>miR-145-5p</i> and <i>miR-382-5p</i>. <b>Results</b>: Elevated <i>hsa-miR-21-5p</i> expression levels and downregulated <i>hsa-miR-145-5p</i> levels were observed in patients with a higher pT stage, lymph node metastasis and advanced pTNM stage. Additionally, <i>hsa-miR-145-5p</i> expression was lower in patients with cardia involvement and a Lauren intestinal-type carcinoma. <i>hsa-miR-382-5p</i> levels were higher in patients with non-mucinous gastric carcinoma. Both <i>hsa-miR-145-5p</i> and <i>hsa-miR-21-5p</i> were predictors of the presence of node metastasis, even when adjusted for pT status. <i>hsa-miR-145-5p</i> was significantly associated with improved survival. <i>hsa-miR-145-5p</i> was significantly associated with an increased probability of surviving 3 years, while increased <i>hsa-miR-21</i> expression was significantly associated with reduced 3-year survival. All these associations were confirmed in multivariate models, which also included pT and M staging. <b>Conclusions</b>: The upregulation of <i>miR-21-5p</i> and downregulation of <i>miR-145-5p</i> are independent prognostic factors for lymph node metastasis and could serve as specific biomarkers of the lymphatic spread of gastric adenocarcinoma. <i>miR-145-5p</i> downregulation is an independent prognostic factor for overall survival.