Downregulation of microRNA-375, combined with upregulation of its target gene Janus kinase 2, predicts unfavorable prognosis in patients with gastric cancer.

MicroRNA (miR)-375 has been reported to function as a tumor suppressor in gastric cancer via targeting Janus kinase 2 (JAK2). Until now, no clinical evidence of miR-375-JAK2 combination in gastric cancer has been documented. Here, quantitative real-time PCR was performed to detect the serum levels of miR-375 and JAK2 mRNA in 100 patients with gastric cancer and 50 healthy controls. Receiver operating characteristic (ROC) analysis was used to assess the predictive diagnostic value of serum miR-375 and/or JAK2 mRNA for gastric cancer. Associations of serum miR-375 and/or JAK2 mRNA levels with various clinicopathological features and prognosis in patients with gastric cancer were also analyzed. As a result, miR-375 expression was significantly downregulated, while JAK2 mRNA expression was dramatically upregulated, in patients' sera of gastric cancer (both P<0.001), compared to healthy controls. Notably, the areas under ROC curve for serum miR-375 and JAK2 discriminating gastric cancer patients from healthy controls were respectively 0.871 (sensitivity = 82.00%, specificity = 72.00%) and 0.864 (sensitivity = 55.00%, specificity = 100.00%). Moreover, miR-375 downregulation and/or JAK2 upregulation were all significantly associated with positive lymph node metastasis, high tumor-node-metastasis stage and the presence of H. pylori infection in patients with gastric cancer (all P<0.05). Furthermore, serum miR-375 and/or JAK2 were all independent prognostic factors for patients with gastric cancer. Importantly, the prognostic value of miR-375-JAK2 combination was more significant than considered alone. Collectively, serum miR-375 and JAK2 combination may be a potential diagnostic and prognostic predictor of gastric cancer. miR-375-JAK2 axis might be a promising candidate for a molecular targeted therapy of this malignancy.