NDRG1 suppresses vasculogenic mimicry and tumor aggressiveness in gastric carcinoma.

摘要

N-myc downstream regulated gene 1 (NDRG1) has been well characterized as a suppressor of metastasis in numerous types of carcinoma. NDRG1 inhibits the metastatic progression of cancer cells via its inhibitory effects on a wide variety of cellular signaling pathways. Vasculogenic mimicry (VM) refers to the unique ability of aggressive tumor cells to mimic the pattern of embryonic vasculogenic networks, and is the main reason for the poor prognosis and failure of antivascular therapy in gastric carcinoma (GC). Tumor cells can mimic the function of endothelial cells to exhibit VM through epithelial-mesenchymal transition (EMT). However, the potential function of NDRG1 in metastatic GC progression in patients has not yet been fully elucidated. To date, data regarding the function of NDRG1 in VM formation in GC have not been reported. The aim of the present study was to elucidate these unknown areas. To this end, 228 samples of human GC were used to identify the protein expression levels of NDRG1, VM-associated proteins and EMT-associated proteins via immunohistochemistry, and their clinical significance was assessed. In addition, the data of 415 patients with GC were collected from The Cancer Genome Atlas database. A functional enrichment analysis concerning NDRG1 was performed using Metascape and the Gene Set Enrichment Analysis (GSEA). In conclusion, the results of the present study indicate that NDRG1 is negatively correlated with poor prognosis through suppression of VM formation in GC. The results of the present study demonstrated that NDRG1 decreases EMT-associated protein expression and that HER2 expression may serve a significant role in this process. The Metascape and GSEA results also indirectly support this conclusion. The present study discusses the status NDRG1 as a prognostic and selective biomarker in GC, as well as current and future NDRG1-targeted therapies.